Molecular Insights into Appetite Control and Neuroendocrine Disease as Risk Factors for Chronic Diseases in Western Countries

Abstract

Environmental factors such as stress, anxiety and depression are important to consider with the global increase in chronic diseases such as cardiovascular diseases, cancer, stroke, obesity, diabetes and neurodegenerative diseases. Brain metabolic diseases associated with conditions such as obesity and diabetes require early intervention with diet, lifestyle and drug therapy to prevent diseases to various organs such as the liver with non alcoholic fatty liver disease (NAFLD) and other organs such as the heart, lungs thyroid, pancreas, brain, kidneys and reproductive systems. Behavioural stress and the molecular mechanisms that are involved in neuroendocrine diseases such as insulin resistance in obesity require attention since associated inflammatory processes early in the disease process have been associated with neurodegenerative diseases. Molecular neuroendocrine disturbances that cause appetite dysregulation and hyperphagia are closely linked to hyperinsulinemia, dyslipidaemia and reduced lifespan. The origins of metabolic diseases that afflict various organs possibly arise from hypothalamic disturbances with loss of control of peripheral endocrine hormones and neuropeptides released from the brain. Diet and drug therapies that are directed to the autonomic nervous system, neuroendocrine and limbic systems may help regulate and integrate leptin and insulin signals involving various neuropeptides associated with chronic diseases such as obesity and diabetes. The understanding of brain circuits and stabilization of neuroanatomical structures in the brain is currently under investigation. Research that is involved in the understanding of diet and drugs in the stabilization of brain structures such as frontostriatal limbic circuits, hypothalamus brainstem circuits and parasympathetic nervous system is required. Information related to neuropeptides and neurotransmitters that are released from the brain and their regulation by therapeutic drugs requires further assessment. The promise of appropriate diets, lifestyle and drugs that target the CNS and peripheral tissues such as the adipose tissue, liver and pancreas may improve the prognosis of chronic diseases such as obesity and diabetes that are also closely associated with neurodegeneration.

Share and Cite:

I. Martins, R. Creegan, W. Lim and R. Martins, "Molecular Insights into Appetite Control and Neuroendocrine Disease as Risk Factors for Chronic Diseases in Western Countries," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 5A, 2013, pp. 11-33. doi: 10.4236/ojemd.2013.35A002.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] B. Caballero, “The Global Epidemic of Obesity: An Overview,” Epidemiologic Reviews, Vol. 29, No. 1, 2007. pp. 1-5. doi:10.1093/epirev/mxm012
[2] K. L. Rennie and S. A. Jebb, “Prevalence of Obesity in Great Britain,” Obesity Reviews, Vol. 6, No. 1, 2005, pp. 11-12. doi:10.1111/j.1467-789X.2005.00164.x
[3] P. T. James, N. Rigby and R. Leach, “The Obesity Epidemic, Metabolic Syndrome and Future Prevention Strategies,” European Journal of Preventive Cardiology, Vol. 11, No. 1, 2004, pp. 3-8. doi:10.1097/01.hjr.0000114707.27531.48
[4] K. M. Flegal, et al., “Association of All-Cause Mortality with Overweight and Obesity Using Standard Body Mass Index Categories: A Systematic Review and Meta-Analysis,” The Journal of the American Medical Association, Vol. 309, No. 1, 2013, pp. 71-82. doi:10.1001/jama.2012.113905
[5] H. Greenberg, S. U. Raymond and S. R. Leeder, “Cardiovascular Disease and Global Health: Threat and Opportunity,” Health Affairs (Millwood), 2005.
[6] G. Bukhman and A. Kidder, “Cardiovascular Disease and Global Health Equity: Lessons from Tuberculosis Control Then and Now,” American Journal of Public Health, Vol. 98, No. 1, 2008, pp. 44-54. doi:10.2105/AJPH.2007.110841
[7] B. Mathew, et al., “Obesity: Effects on Cardiovascular Disease and Its Diagnosis,” Journal of the American Board of Family Medicine, Vol. 21, No. 6, 2008, pp. 562-568. doi:10.3122/jabfm.2008.06.080080
[8] C. J. Lavie, M. R. Mehra and R. V. Milani, “Obesity and Heart Failure Prognosis: Paradox or Reverse Epidemiology?” European Heart Journal, Vol. 26, No. 1, 2005, pp. 5-7. doi:10.1093/eurheartj/ehi055
[9] R. L. C. Matteri, J. A. Carroll and C. J. Dyer, “Neuroendocrine Responses to Stress,” CAB International 2000, 2000.
[10] F. S. Luppino, et al., “Overweight, Obesity, and Depression: A Systematic Review and Meta-Analysis of Longitudinal Studies,” Archives of General Psychiatry, Vol. 67, No. 3, 2010, pp. 220-229. doi:10.1001/archgenpsychiatry.2010.2
[11] T. W. Strine, et al., “The Association of Depression and Anxiety with Obesity and Unhealthy Behaviors among Community-Dwelling US Adults,” General Hospital Psychiatry, Vol. 30, No. 2, 2008, pp. 127-137. doi:10.1016/j.genhosppsych.2007.12.008
[12] B. Jeanrenaud, S. Halimi and G. Van der Werve, “Neuroendocrine Disorders Seen as Triggers of the Triad: Obesity-Insulin Resistance-Abnormal Glucose Tolerance,” Diabetes/Metabolism Reviews, Vol. 1, No. 3, 2009, pp. 261-291. doi:10.1002/dmr.5610010303
[13] E. Susaki and K. I. Nakayama, “An Animal Model Manifesting Neurodegeneration and Obesity,” Aging, Vol. 2, No. 7, 2010, pp. 453-456.
[14] P. Bjorntorp, “Neuroendocrine Perturbations as a Cause of Insulin Resistance,” Diabetes/Metabolism Research and Reviews, Vol. 15, No. 6, 1999, pp. 427-441. doi:10.1002/(SICI)1520-7560(199911/12)15:6<427::AID-DMRR68>3.0.CO;2-C
[15] P. Bjorntorp, “Insulin Resistance: The Consequence of a Neuroendocrine Disturbance?” International Journal of Obesity and Related Metabolic Disorders, Vol. 19, Suppl. 1, 1995, pp. S6-S10.
[16] M. Sjostrand, and J. W. Eriksson, “Neuroendocrine Mechanisms in Insulin Resistance,” Molecular and Cellular Endocrinology, Vol. 297, No. 1-2, 2009, pp. 104-111. doi:10.1016/j.mce.2008.05.010
[17] J. Gimble, A. Ptitsyn and Z. Floyd, “Circadian Rhythms in Adipose Tissue,” Endocrine Abstracts, Vol. 29, Suppl. 50, 2012, p. 3.
[18] J. M. Gimble, et al., “Circadian Rhythms in Adipose Tissue: An Update,” Current Opinion in Clinical Nutrition & Metabolic Care, Vol. 14, No. 6, 2011, pp. 554-561. doi:10.1097/MCO.0b013e32834ad94b
[19] P. Loria, et al., “Endocrine and Liver Interaction: The Role of Endocrine Pathways in NASH,” Nature Reviews. Gastroenterology & Hepatology, Vol. 6, No. 4, 2009, pp. 236-247.
[20] P. Schrauwen, “Lipid-Induced Cell Stress and Insulin Resistance,” Scandinavian Journal of Food and Nutrition, Vol. 50, Suppl. 2, 2006, pp. 62-67. doi:10.1080/17482970601066132
[21] J. P. Felber, et al., “Role of Lipid Oxidation in Pathogenesis of Insulin Resistance of Obesity and Type II Diabetes,” Diabetes, Vol. 36, No. 11, 1987, pp. 1341-1350.
[22] M. F. Gregor and G. S. Hotamisligil, “Inflammatory Mechanisms in Obesity,” Annual Review of Immunology, Vol. 29, 2011, pp. 415-445. doi:10.1146/annurev-immunol-031210-101322
[23] C. de Luca and J. M. Olefsky, “Inflammation and Insulin Resistance,” FEBS Letters, Vol. 582, No. 1, 2008, pp. 97-105. doi:10.1016/j.febslet.2007.11.057
[24] J. K. Suagee, B. A. Corl and R. J. Geor, “A Potential Role for Pro-Inflammatory Cytokines in the Development of Insulin Resistance in Horses,” Animals, Vol. 2, No. 2, 2012, pp. 243-260.doi:10.3390/ani2020243
[25] B. E. Wisse, “The Inflammatory Syndrome: The Role of Adipose Tissue Cytokines in Metabolic Disorders Linked to Obesity,” Journal of the American Society of Nephrology, Vol. 15, No. 11, 2004, pp. 2792-2800. doi:10.1097/01.ASN.0000141966.69934.21
[26] J. K. Kiecolt-Glaser, et al., “Chronic Stress and Age-Related Increases in the Proinflammatory Cytokine IL-6,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 15, 2003, pp. 9090-9095. doi:10.1073/pnas.1531903100
[27] H. Anisman and Z. Merali, “Cytokines, Stress, and Depressive Illness,” Brain, Behavior and Immunity, Vol. 16, No. 5, 2002, pp. 513-524.
[28] A. Marette, “Mediators of Cytokine-Induced Insulin Resistance in Obesity and Other Inflammatory Settings,” Current Opinion in Clinical Nutrition & Metabolic Care, Vol. 5, No. 4, 2002, pp. 377-383. doi:10.1097/00075197-200207000-00005
[29] N. Ouchi, et al., “Adipokines in Inflammation and Metabolic Disease,” Nature Reviews. Immunology, Vol. 11, No. 2, 2011, pp. 85-97.
[30] V. Mohamed-Ali, J. H. Pinkney and S. W. Coppack, “Adipose Tissue as an Endocrine and Paracrine Organ,” International Journal of Obesity and Related Metabolic Disorders, Vol. 22, No. 12, 1998, pp. 1145-1158.
[31] F. D. Popescu, “Cytokines and Neuropeptides in the Relationship Stress-Immunity,” INFO Medica, Vol. 1, No. 143, 2008, pp. 8-10.
[32] M. G. Myers Jr., et al., “Obesity and Leptin Resistance: Distinguishing Cause from Effect,” Trends in Endocrinology & Metabolism, Vol. 21, No. 11, 2010, pp. 643-651. doi:10.1016/j.tem.2010.08.002
[33] C. S. Mantzoros, “The Role of Leptin in Human Obesity and Disease: A Review of Current Evidence,” Annals of Internal Medicine, Vol. 130, No. 8, 1999, pp. 671-680. doi:10.7326/0003-4819-130-8-199904200-00014
[34] S. M. de la Monte, et al., “Insulin Resistance and Neurodegeneration: Roles of Obesity, Type 2 Diabetes Mellitus and Non-Alcoholic Steatohepatitis,” Current Opinion in Investigational Drugs, Vol. 10, No. 10, 2009, pp. 1049-1060.
[35] E. Stice, et al., “Psychological and Behavioral Risk Factors for Obesity Onset in Adolescent Girls: A Prospective Study,” Journal of Consulting and Clinical Psychology, Vol. 73, No. 2, 2005, pp. 195-202. doi:10.1037/0022-006X.73.2.195
[36] J. Brody, “The Global Epidemic of Childhood Obesity: Poverty, Urbanization and Nutrition,” Nutrition Bytes, Vol. 8, No. 2, 2002, pp. 1-7.
[37] B. Biondi, “Thyroid and Obesity: An Intriguing Relationship,” The Journal of Clinical Endocrinology & Metabolism, Vol. 95, No. 8, 2010, pp. 3614-3617. doi:10.1210/jc.2010-1245
[38] E. N. Pearce, “Thyroid Hormone and Obesity,” Current Opinion in Endocrinology, Diabetes, and Obesity, Vol. 19, No. 5, 2012, pp. 408-413.
[39] A. Verma, et al., “Hypothyroidism and Obesity. Cause or Effect?” Saudi Medical Journal, Vol. 29, No. 8, 2008, pp. 1135-1138.
[40] M. Rotondi, F. Magri and L. Chiovato, “Thyroid and Obesity: Not a One-Way Interaction,” The Journal of Clinical Endocrinology & Metabolism, Vol. 96, No. 2, 2011, pp. 344-346. doi:10.1210/jc.2010-2515
[41] T. Reinehr, “Obesity and Thyroid Function,” Molecular and Cellular Endocrinology, Vol. 316, No. 2, 2010, pp. 165-171. doi:10.1016/j.mce.2009.06.005
[42] G. Boden, “Free Fatty Acids as Target for Therapy. Diabetes and the Endocrine Pancreas II,” Current Opinion in Endocrinology & Diabetes, Vol. 11, No. 5, 2004, pp. 258-263. doi:10.1097/01.med.0000141928.95173.63
[43] R. Belfort, et al., “Dose-Response Effect of Elevated Plasma Free Fatty Acid on Insulin Signalling,” Diabetes, Vol. 54, No. 6, 2005, pp. 1640-1648. doi:10.2337/diabetes.54.6.1640
[44] X. L. Wang, et al., “Free Fatty Acids Inhibit Insulin Signaling-Stimulated Endothelial Nitric Oxide Synthase Activation through Upregulating PTEN or Inhibiting Akt Kinase,” Diabetes, Vol. 55, No. 8, 2006, pp. 2301-2310. doi:10.2337/db05-1574
[45] W. L. Holland and S. A. Summers, “Sphingolipids, Insulin Resistance, and Metabolic Disease: New Insights from in Vivo Manipulation of Sphingolipid Metabolism,” Endocrine Reviews, Vol. 29, No. 4, 2008, pp. 381-402. doi:10.1210/er.2007-0025
[46] C. Lipina and H. S. Hundal, “Sphingolipids: Agents Provocateurs in the Pathogenesis of Insulin Resistance,” Diabetologia, Vol. 54, No. 7, 2011, pp. 1596-1607. doi:10.1007/s00125-011-2127-3
[47] C. Schmitz-Peiffer, “Targeting Ceramide Synthesis to Reverse Insulin Resistance,” Diabetes, Vol. 59, No. 10, 2010, pp. 2351-2353. doi:10.2337/db10-0912
[48] J. M. Gill and N. Sattar, “Ceramides: A New Player in the Inflammation-Insulin Resistance Paradigm?” Diabetologia, Vol. 52, No. 12, 2009, pp. 2475-2477. doi:10.1007/s00125-009-1546-x
[49] M. Kolak, et al., “Adipose Tissue Inflammation and Increased Ceramide Content Characterize Subjects with High Liver Fat Content Independent of Obesity,” Diabetes, Vol. 56, No. 8, 2007, pp. 1960-1968. doi:10.2337/db07-0111
[50] F. Samad, et al., “Adipose Tissue and Ceramide Biosynthesis in the Pathogenesis of Obesity,” Advances in Experimental Medicine and Biology, Vol. 721, 2011, pp. 67-86. doi:10.1007/978-1-4614-0650-1_5
[51] S. A. Young, et al., “Sphingolipid and Ceramide Homeostasis: Potential Therapeutic Targets,” Biochemistry Research International, Vol. 2012, 2012, Article ID: 248135.
[52] R. N. Bergman and M. Ader, “Free Fatty Acids and Pathogenesis of Type 2 Diabetes Mellitus,” Trends in Endocrinology & Metabolism, Vol. 11, No. 9, 2000, pp. 351-356. doi:10.1016/S1043-2760(00)00323-4
[53] P. J. Meikle and M. J. Christopher, “Lipidomics Is Providing New Insight into the Metabolic Syndrome and Its Sequelae,” Current Opinion in Lipidology, Vol. 22, No. 3, 2011, pp. 210-215. doi:10.1097/MOL.0b013e3283453dbe
[54] K. H. Pietilainen, et al., “Acquired Obesity Is Associated with Changes in the Serum Lipidomic Profile Independent of Genetic Effects—A Monozygotic Twin Study,” PLoS One, Vol. 2, No. 2, 2007, p. e218. doi:10.1371/journal.pone.0000218
[55] A. Kontush and M. J. Chapman, “Lipidomics as a Tool for the Study of Lipoprotein Metabolism,” Current Atherosclerosis Reports, Vol. 12, No. 3, 2010, pp. 194-201. doi:10.1007/s11883-010-0100-0
[56] P. Puri, et al., “A Lipidomic Analysis of Nonalcoholic Fatty Liver Disease,” Hepatology, Vol. 46, No. 4, 2007, pp. 1081-1090. doi:10.1002/hep.21763
[57] W. L. Lim, et al., “Effects of a High-Fat, High-Cholesterol Diet on Brain Lipid Profiles in Apolipoprotein E Epsilon3 and Epsilon4 Knock-In Mice,” Neurobiology of Aging, Vol. 34, No. 9, 2013, pp. 2217-2224. doi:10.1016/j.neurobiolaging.2013.03.012
[58] I. J. Martins, K. M. Wood, A. Z. Fernandez, K. Taddei, R. N. Martins, “Anti-Oxidative Acyl CoA Cholesterol Acyltransferase Inhibitor AVASIMIBE Reduces the Impact of a High Cholesterol Diet on Brain Lipid Peroxidation in Mice,” ADPD, Florence, 2013. www.kenes.com.
[59] M. O. Grimm, et al., “Trans Fatty Acids Enhance Amyloidogenic Processing of the Alzheimer Amyloid Precursor Protein (APP),” The Journal of Nutritional Biochemistry, Vol. 23, No. 10, 2012, pp. 1214-1223. doi:10.1016/j.jnutbio.2011.06.015
[60] M. O. Grimm, et al., “Effect of Different Phospholipids on alpha-Secretase Activity in the Non-Amyloidogenic Pathway of Alzheimer’s Disease,” International Journal of Molecular Sciences, Vol. 14, No. 3, 2013, pp. 5879-5898. doi:10.3390/ijms14035879
[61] L. Arana, et al., “Ceramide and Ceramide 1-Phosphate in Health and Disease,” Lipids in Health and Disease, Vol. 9, 2010, p. 15. doi:10.1186/1476-511X-9-15
[62] R. L. Creegan, W. L. F. Lin, I. J. Martins, S. M. Laws, V. Gupta, S. Rainey-Smith, et al., “Plasma Lipidomics in Alzheimer’s disease (AD); Preliminary Data from the Australian Imaging, Biomarkers and Lifestyle Study (AIBL) of Ageing,” ADPD, Florence, 2013. www.kenes.com
[63] J. T. Lee, et al., “Amyloid-Beta Peptide Induces Oligodendrocyte Death by Activating the Neutral Sphingomyelinase-Ceramide Pathway,” The Journal of Cell Biology, Vol. 164, No. 1, 2004, pp. 123-131. doi:10.1083/jcb.200307017
[64] L. Puglielli, et al., “Ceramide Stabilizes Beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1 and Promotes Amyloid Beta-Peptide Biogenesis,” The Journal of Biological Chemistry, Vol. 278, No. 22, 2003, pp. 19777-. doi:10.1074/jbc.M300466200
[65] T. H. Jones and R. L. Kennedy, “Cytokines and Hypothalamic-Pituitary Function,” Cytokine, Vol. 5, No. 6, 1993, pp. 531-538. doi:10.1016/S1043-4666(05)80001-8
[66] M. Bentivoglio, et al., “The Aging Suprachiasmatic Nucleus and Cytokines: Functional, Molecular, and Cellular Changes in Rodents,” Chronobiology International, Vol. 23, No. 1-2, 2006, pp. 437-449. doi:10.1080/07420520500545797
[67] M. Bentivoglio, M. Nygard, M. Palomba and K. Kristensson, “The Biological Clock in Inflammation and Sleep Switch Alterations,” Neuroimmunology of Sleep, Vol. 1, 2007, pp. 87-96. doi:10.1007/978-0-387-69146-6_4
[68] J. B. Buchanan and R. W. Johnson, “Regulation of Food Intake by Inflammatory Cytokines in the Brain,” Neuroendocrinology, Vol. 86, No. 3, 2007, pp. 183-190. doi:10.1159/000108280
[69] B. J. Mickey, et al., “Emotion Processing, Major Depression, and Functional Genetic Variation of Neuropeptide Y,” Archives of General Psychiatry, Vol. 68, No. 2, 2011, pp. 158-166. doi:10.1001/archgenpsychiatry.2010.197
[70] A. Thorsell, “Brain Neuropeptide Y and CorticotropinReleasing Hormone in Mediating Stress and Anxiety,” Experimental Biology and Medicine, Vol. 235, No. 10, 2010, pp. 1163-1167. doi:10.1258/ebm.2010.009331
[71] Y. Koutmani, et al., “Corticotropin-Releasing Hormone Exerts Direct Effects on Neuronal Progenitor Cells: Implications for Neuroprotection,” Molecular Psychiatry, Vol. 18, No. 3, 2013, pp. 300-307. doi:10.1038/mp.2012.198
[72] G. Nikisch, et al., “Neuropeptide Y and CorticotropinReleasing Hormone in CSF Mark Response to Antidepressive Treatment with Citalopram,” The International Journal of Neuropsychopharmacology, Vol. 8, No. 3, 2005, pp. 403-410. doi:10.1017/S1461145705005158
[73] D. A. Haas and S. R. George, “Neuropeptide Y-Induced Effects on Hypothalamic Corticotropin-Releasing Factor Content and Release Are Dependent on Noradrenergic/ Adrenergic Neurotransmission,” Brain Research, Vol. 498, No. 2, 1989, pp. 333-338. doi:10.1016/0006-8993(89)91112-8
[74] M. Jang and D. R. Romsos, “Neuropeptide Y and Corticotropin-Releasing Hormone Concentrations within Specific Hypothalamic Regions of Lean but not ob/ob Mice Respond to Food-Deprivation and Refeeding,” The Journal of Nutrition, Vol. 128, No. 12, 1998, pp. 2520-2525.
[75] J. R. Glowa, et al., “Effects of Corticotropin Releasing Hormone on Appetitive Behaviours,” Peptides, Vol. 13, No. 3, 1992, pp. 609-621. doi:10.1016/0196-9781(92)90097-M
[76] T. Katsuyoshi, “Hormonal Mechanism of Appetite Control and Clinical Application. Basis: Hormone and Appetite Control. Role of CRH, Urocortin and Glucocorticoid in the Regulation of Food Intake,” Clinical Endocrinology, Vol. 53, 2005, pp. 361-370.
[77] R. Denis, “The Role of Corticotropin-Releasing Hormone in the Regulation of Energy Balance,” Current Opinion in Endocrinology & Diabetes, Vol. 6, No. 1, 1999, p. 10. doi:10.1097/00060793-199902000-00003
[78] D. Richard, Q. Huang and E. Timofeeva, “The Corticotropin-Releasing Hormone System in the Regulation of Energy Balance in Obesity,” International Journal of Obesity, Vol. 24, Suppl. 2, 2000, pp. S36-S39. doi:10.1038/sj.ijo.0801275
[79] K. Roguski, et al., “Leptin Modulates the CorticotropinReleasing Hormone (CRH) Action on Progesterone Release from Cultured Rat Granulosa Cells,” Neuro Endocrinology Letters, Vol. 21, No. 5, 2000, pp. 383-389.
[80] K. Arvaniti, Q. Huang and D. Richard, “Effects of Leptin and Corticosterone on the Expression of CorticotropinReleasing Hormone, Agouti-Related Protein, and Proopiomelanocortin in the Brain of ob/ob Mouse,” Neuroendocrinology, Vol. 73, No. 4, 2001, pp. 227-236. doi:10.1159/000054639
[81] H. E. Auvinena, J. A. Romijn, N. R. Biermasza, et al., “The Effects of High Fat Diet on the Basal Activity of the Hypothalmus-Pituitary-Adrenal Axis in Mice,” Journal of Endocrinology, Vol. 214, No. 2, 2012, pp. 191-197.
[82] M. Chavez, et al., “Effect of a High-Fat Diet on Food Intake and Hypothalamic Neuropeptide Gene Expression in Streptozotocin Diabetes,” The Journal of Clinical Investigation, Vol. 102, No. 2, 1998, pp. 340-346. doi:10.1172/JCI603
[83] H. Husum and A. A. Mathe, “Early Life Stress Changes Concentrations of Neuropeptide Y and Corticotropin-Releasing Hormone in Adult Rat Brain. Lithium Treatment Modifies These Changes,” Neuropsychopharmacology, Vol. 27, No. 5, 2002, pp. 756-764. doi:10.1016/S0893-133X(02)00363-9
[84] J. M. Stafford, et al., “Central Nervous System Neuropeptide Y Signaling Modulates VLDL Triglyceride Secretion,” Diabetes, Vol. 57, No. 6, 2008, pp. 1482-1490. doi:10.2337/db07-1702
[85] J. J. Geerling, et al., “Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (VLDL) Production in Mice,” PLoS One, Vol. 8, No. 2, 2013, p. e55217. doi:10.1371/journal.pone.0055217
[86] K. A. Paschos, et al., “Corticotropin-Releasing Hormone Receptors Mediate Opposing Effects in Cholestasis-Induced Liver Cell Apoptosis,” Endocrinology, Vol. 151, No. 4, 2010, pp. 1704-1712. doi:10.1210/en.2009-1208
[87] N. Bayatti and C. Behl, “The Neuroprotective Actions of Corticotropin Releasing Hormone,” Ageing Research Reviews, Vol. 4, No. 2, 2005, pp. 258-270. doi:10.1016/j.arr.2005.02.004
[88] J. E. Kang, et al., “Acute Stress Increases Interstitial Fluid Amyloid-Beta via Corticotropin-Releasing Factor and Neuronal Activity,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 25, 2007, pp. 10673-10678. doi:10.1073/pnas.0700148104
[89] W. A. Pedersen, et al., “Corticotropin-Releasing Hormone Protects Neurons against Insults Relevant to the Pathogenesis of Alzheimer’s Disease,” Neurobiology of Disease, Vol. 8, No. 3, 2001, pp. 492-503. doi:10.1006/nbdi.2001.0395
[90] F. Lezoualc’h, et al., “Corticotropin-Releasing HormoneMediated Neuroprotection against Oxidative Stress Is Associated with the Increased Release of Non-Amyloidogenic Amyloid Beta Precursor Protein and with the Suppression of Nuclear Factor-kappaB,” Molecular Endocrinology, Vol. 14, No. 1, 2000, pp. 147-159. doi:10.1210/me.14.1.147
[91] D. Rat, et al., “Neuropeptide Pituitary Adenylate CyclaseActivating Polypeptide (PACAP) Slows Down Alzheimer’s Disease-Like Pathology in Amyloid Precursor Protein-Transgenic Mice,” The FASEB Journal, Vol. 25, No. 9, 2011, pp. 3208-3218. doi:10.1096/fj.10-180133
[92] R. Postina, “Activation of Alpha-Secretase Cleavage,” Journal of Neurochemistry, Vol. 120, Suppl. 1, 2012, pp. 46-54. doi:10.1111/j.1471-4159.2011.07459.x
[93] S. Parvathy, et al., “Atorvastatin-Induced Activation of Alzheimer’s Alpha Secretase Is Resistant to Standard Inhibitors of Protein Phosphorylation-Regulated Ectodomain Shedding,” Journal of Neurochemistry, Vol. 90, No. 4, 2004, pp. 1005-1010. doi:10.1111/j.1471-4159.2004.02521.x
[94] D. M. Skovronsky, et al., “Protein Kinase C-Dependent Alpha-Secretase Competes with Beta-Secretase for Cleavage of Amyloid-Beta Precursor Protein in the TransGolgi Network,” The Journal of Biological Chemistry, Vol. 275, No. 4, 2000, pp. 2568-2575. doi:10.1074/jbc.275.4.2568
[95] S. E. Hammack, et al., “Roles for Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Expression and Signaling in the Bed Nucleus of the Stria Terminalis (BNST) in Mediating the Behavioral Consequences of Chronic Stress,” Journal of Molecular Neuroscience, Vol. 4, No. 3, 2010, pp. 327-340. doi:10.1007/s12031-010-9364-7
[96] L. Mounien, et al., “Pituitary Adenylate Cyclase-Activating Polypeptide Inhibits Food Intake in Mice through Activation of the Hypothalamic Melanocortin System,” Neuropsychopharmacology, Vol. 34, No. 2, 2009, pp. 424-435. doi:10.1038/npp.2008.73
[97] J. E. Morley, et al., “Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) Reduces Food Intake in Mice,” Peptides, Vol. 13, No. 6, 1992, pp. 1133-1135. doi:10.1016/0196-9781(92)90019-Y
[98] X. Qu, J. P. Seale and R. Donnelly, “Tissue and IsoformSelective Activation of Protein Kinase C in Insulin-Resistant Obese Zucker Rats-Effects of Feeding,” Journal of Endocrinology, Vol. 162, No. 2, 1999, pp. 207-214. doi:10.1677/joe.0.1620207
[99] M. Sastre, T. Klockgether and M. T. Heneka, “Contribution of Inflammatory Processes to Alzheimer’s Disease: Molecular Mechanisms,” International Journal of Developmental Neuroscience, Vol. 24, No. 2-3, 2006, pp. 167-176. doi:10.1016/j.ijdevneu.2005.11.014
[100] N. S. Patel, et al., “Inflammatory Cytokine Levels Correlate with Amyloid Load in Transgenic Mouse Models of Alzheimer’s Disease,” Journal of Neuroinflammation, Vol. 2, No. 1, 2005, p. 9. doi:10.1186/1742-2094-2-9
[101] S. Askarova, X. Yang and J. C. Lee, “Impacts of Membrane Biophysics in Alzheimer’s Disease: From Amyloid Precursor Protein Processing to Abeta Peptide-Induced Membrane Changes,” International Journal of Alzheimer’s Disease, Vol. 2011, 2011, Article ID: 134971.
[102] N. Pannacciulli, et al., “Brain Abnormalities in Human Obesity: A Voxel-Based Morphometric Study,” Neuroimage, Vol. 31, No. 4, 2006, pp. 1419-1425. doi:10.1016/j.neuroimage.2006.01.047
[103] C. A. Raji, et al., “Brain Structure and Obesity,” Human Brain Mapping, Vol. 31, No. 3, 2010, pp. 353-364.
[104] J. P. Thaler and M. W. Schwartz, “Minireview: Inflammation and Obesity Pathogenesis: The Hypothalamus Heats Up,” Endocrinology, Vol. 151, No. 9, 2010, pp. 4109-4115. doi:10.1210/en.2010-0336
[105] A. A. Kandutsch, H. J. Heiniger and H. W. Chen, “Effects of 25-Hydroxycholesterol and 7-Ketocholesterol, Inhibitors of Sterol Synthesis, Administered Orally to Mice,” Biochimica et Biophysica Acta, Vol. 486, No. 2, 1977, pp. 260-272. doi:10.1016/0005-2760(77)90022-4
[106] K. Shimizu, et al., “Anti-Obesity Effect of Phosphatidylinositol on Diet-Induced Obesity in Mice,” Journal of Agricultural and Food Chemistry, Vol. 58, No. 21, 2010, pp. 11218-11225. doi:10.1021/jf102075j
[107] A. S. Metlakunta, M. Sahu and A. Sahu, “Hypothalamic Phosphatidylinositol 3-Kinase Pathway of Leptin Signaling Is Impaired during the Development of Diet-Induced Obesity in FVB/N Mice,” Endocrinology, Vol. 149, No. 3, 2008, pp. 1121-1128. doi:10.1210/en.2007-1307
[108] J. P. Warne, et al., “Impairment of Central Leptin-Mediated PI3K Signaling Manifested as Hepatic Steatosis Independent of Hyperphagia and Obesity,” Cell Metabolism, Vol. 14, No. 6, 2011, pp. 791-803. doi:10.1016/j.cmet.2011.11.001
[109] J. W. Hill, et al., “Acute Effects of Leptin Require PI3K Signaling in Hypothalamic Proopiomelanocortin Neurons in Mice,” The Journal of Clinical Investigation, Vol. 118, No. 5, 2008, pp. 1796-1805. doi:10.1172/JCI32964
[110] K. D. Niswender, et al., “Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus: A Key Mediator of Insulin-Induced Anorexia,” Diabetes, Vol. 52, No. 2, 2003, pp. 227-231. doi:10.2337/diabetes.52.2.227
[111] S. Gao, et al., “Important Roles of Brain-Specific Carnitine Palmitoyltransferase and Ceramide Metabolism in Leptin Hypothalamic Control of Feeding,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 23, 2011, pp. 9691-9696. doi:10.1073/pnas.1103267108
[112] X. F. Gao, W. Chen, X. P. Kong, A. M. Xu, Z. G. Wang, G. Sweeney and D. Wu, “Enhanced Susceptibility of Cpt1c Knockout Mice to Glucose Intolerance Induced by a High-Fat Diet Involves Elevated Hepatic Gluconeogenesis and Decreased Skeletal Muscle Glucose Uptake,” The Journal of Biological Chemistry, Vol. 287, No. 25, 2012, pp. 212-243.
[113] M. D. Lane, et al., “Regulation of Food Intake and Energy Expenditure by Hypothalamic Malonyl-CoA,” International Journal of Obesity, Vol. 32, Suppl. 4, 2008, pp. S49-S54. doi:10.1038/ijo.2008.123
[114] S. Ramirez, et al., “Hypothalamic Ceramide Levels Regulated by CPT1C Mediate the Orexigenic Effect of Ghrelin,” Diabetes, Vol. 62, No. 7, 2013, pp. 2329-2337. doi:10.2337/db12-1451
[115] P. Carrasco, et al., “Ceramide Levels Regulated by Carnitine Palmitoyltransferase 1C Control Dendritic Spine Maturation and Cognition,” The Journal of Biological Chemistry, Vol. 287, No. 25, 2012, pp. 21224-21232. doi:10.1074/jbc.M111.337493
[116] Z. Hu, et al., “A Role for Hypothalamic Malonyl-CoA in the Control of Food Intake,” The Journal of Biological Chemistry, Vol. 280, No. 48, 2005, pp. 39681-39683. doi:10.1074/jbc.C500398200
[117] S. Gao, et al., “Malonyl-CoA Mediates Leptin Hypothalamic Control of Feeding Independent of Inhibition of CPT-1a,” American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, Vol. 301, No. 1, 2011, pp. R209-R217. doi:10.1152/ajpregu.00092.2011
[118] M. J. Wolfgang, et al., “The Brain-Specific Carnitine Palmitoyltransferase-1c Regulates Energy Homeostasis,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 19, 2006, pp. 7282-7287. doi:10.1073/pnas.0602205103
[119] R. Lage, et al., “Ghrelin Effects on Neuropeptides in the Rat Hypothalamus Depend on Fatty Acid Metabolism Actions on BSX but Not on Gender,” The FASEB Journal, Vol. 24, No. 8, 2010, pp. 2670-2679. doi:10.1096/fj.09-150672
[120] L. Herrero, et al., “Alteration of the Malonyl-CoA/Carnitine Palmitoyltransferase I Interaction in the Beta-Cell Impairs Glucose-Induced Insulin Secretion,” Diabetes, Vol. 54, No. 2, 2005, pp. 462-471. doi:10.2337/diabetes.54.2.462
[121] M. D. Lane and S. H. Cha, “Effect of Glucose and Fructose on Food Intake via Malonyl-CoA Signaling in the Brain,” Biochemical and Biophysical Research Communications, Vol. 382, No. 1, 2009, pp. 1-5. doi:10.1016/j.bbrc.2009.02.145
[122] M. J. Wolfgang, et al., “Regulation of Hypothalamic Malonyl-CoA by Central Glucose and Leptin,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 104, No. 49, 2007, pp. 19285-19290. doi:10.1073/pnas.0709778104
[123] F. Pintus, G. Floris and A. Rufini, “Nutrient Availability Links Mitochondria, Apoptosis, and Obesity,” Aging, Vol. 4, No. 11, 2012, pp. 734-741.
[124] W. I. Sivitz, “Mitochondria Dysfunction in Obesity and Diabetes,” Endocrinology, Vol. 6, No. 1, 2010, pp. 20-27.
[125] P. L. Yau, et al., “Obesity and Metabolic Syndrome and Functional and Structural Brain Impairments in Adolescence,” Pediatrics, Vol. 130, No. 4, 2012, pp. e856-e864. doi:10.1542/peds.2012-0324
[126] J. J. Hillebrand, D. de Wied and R. A. Adan, “Neuropeptides, Food Intake and Body Weight Regulation: A Hypothalamic Focus,” Peptides, Vol. 23, No. 12, 2002, pp. 2283-2306. doi:10.1016/S0196-9781(02)00269-3
[127] M. W. Schwartz, “Central Nervous System Control of Food Intake,” Nature, Vol. 404, 2007, pp. 661-671.
[128] B. C. Field, O. B. Chaudhri and S. R. Bloom, “Obesity Treatment: Novel Peripheral Targets,” British Journal of Clinical Pharmacology, Vol. 68, No. 6, 2009, pp. 830-843. doi:10.1111/j.1365-2125.2009.03522.x
[129] T. J. Bartness and C. K. Song, “Brain-Adipose Tissue Neural Crosstalk,” Physiology & Behavior, Vol. 91, No. 4, 2007, pp. 343-351. doi:10.1016/j.physbeh.2007.04.002
[130] R. S. Ahima and D. A. Antwi, “Brain Regulation of Appetite and Satiety,” Endocrinology and Metabolism Clinics of North America, Vol. 37, No. 4, 2008, pp. 811-823. doi:10.1016/j.ecl.2008.08.005
[131] H. Zheng, et al., “Appetite Control and Energy Balance Regulation in the Modern World: Reward-Driven Brain Overrides Repletion Signals,” International Journal of Obesity, Vol. 33, Suppl. 2, 2009, pp. S8-S13. doi:10.1038/ijo.2009.65
[132] P. J. Havel, “Peripheral Signals Conveying Metabolic Information to the Brain: Short-Term and Long-Term Regulation of Food Intake and Energy Homeostasis,” Experimental Biology and Medicine, Vol. 226, No. 11, 2001, pp. 963-977.
[133] A. J. Bruce-Keller, J. N. Keller and C. D. Morrison, “Obesity and Vulnerability of the CNS,” Biochimica et Biophysica Acta, Vol. 1792, No. 5, 2009, pp. 395-400. doi:10.1016/j.bbadis.2008.10.004
[134] K. Suzuki, C. N. Jayasena and S. R. Bloom, “Obesity and Appetite Control,” Experimental Diabetes Research, Vol. 2012, 2012, Article ID: 824305.
[135] C. X. Yi, et al., “Ventromedial Arcuate Nucleus Communicates Peripheral Metabolic Information to the Suprachiasmatic Nucleus,” Endocrinology, Vol. 147, No. 1, 2006, pp. 283-294. doi:10.1210/en.2005-1051
[136] O. B. Chaudhri, K. Wynne and S. R. Bloom, “Can Gut Hormones Control Appetite and Prevent Obesity?” Diabetes Care, Vol. 31, Suppl. 2, 2008, pp. S284-S289. doi:10.2337/dc08-s269
[137] S. Chearskul, et al., “Obesity and Appetite-Related Hormones,” Journal of the Medical Association of Thailand, Vol. 95, No. 11, 2012, pp. 1472-1479.
[138] K. Suzuki, C. N. Jayasena and S. R. Bloom, “The Gut Hormones in Appetite Regulation,” Journal of Obesity, Vol. 2011, 2011, Article ID: 528401.
[139] K. A. Simpson and S. R. Bloom, “Appetite and Hedonism: Gut Hormones and the Brain,” Endocrinology and Metabolism Clinics of North America, Vol. 39, No. 4, 2010, pp. 729-743. doi:10.1016/j.ecl.2010.08.001
[140] C. X. Yi and M. H. Tschop, “Brain-Gut-Adipose-Tissue Communication Pathways at a Glance,” Diseases Models & Mechanisms, Vol. 5, No. 5, 2012, pp. 583-587. doi:10.1242/dmm.009902
[141] P. C. Konturek, T. Brzozowski and S. J. Konturek, “Gut Clock: Implication of Circadian Rhythms in the Gastrointestinal Tract,” Journal of Physiology and Pharmacology, Vol. 62, No. 2, 2011, pp. 139-150.
[142] C. Dibner, U. Schibler and U. Albrecht, “The Mammalian Circadian Timing System: Organization and Coordination of Central and Peripheral Clocks,” Annual Review of Physiology, Vol. 72, 2010, pp. 517-549. doi:10.1146/annurev-physiol-021909-135821
[143] O. Froy, “Metabolism and Circadian Rhythms—Implications for Obesity,” Endocrine Reviews, Vol. 31, No. 1, 2010, pp. 1-24. doi:10.1210/er.2009-0014
[144] O. Froy, “Circadian Rhythms and Obesity in Mammals,” ISRN Obesity, Vol. 2012, 2012, Article ID: 437198. doi:10.5402/2012/437198
[145] J. Mendoza and E. Challet, “Brain Clocks: From the Suprachiasmatic Nuclei to a Cerebral Network,” Neuroscientist, Vol. 15, No. 5, 2009, pp. 477-488. doi:10.1177/1073858408327808
[146] C. B. Saper, et al., “The Hypothalamic Integrator for Circadian Rhythms,” Trends in Neurosciences, Vol. 28, No. 3, 2005, pp. 152-157. doi:10.1016/j.tins.2004.12.009
[147] M. Lee and J. Korner, “Review of Physiology, Clinical Manifestations, and Management of Hypothalamic Obesity in Humans,” Pituitary, Vol. 12, No. 2, 2009, pp. 87-95. doi:10.1007/s11102-008-0096-4
[148] S. Baloyannis, “The Hypothalamus in Alzheimer’s Disease: A Study with Silver Impregnation Techniques and Electron Microscope,” Alzheimer’s and Dementia, Vol. 5, No. 4, 2009, p. 40. doi:10.1016/j.jalz.2009.05.644
[149] D. F. Swaab, et al., “The Human Hypothalamus in Development, Sexual Differentiation, Aging and Alzheimer’s Disease,” Progress in Brain Research, Vol. 91, 1992, pp. 465-472. doi:10.1016/S0079-6123(08)62369-9
[150] J. A. van de Nes, et al., “The Distribution of Alz-50 Immunoreactivity in the Hypothalamus and Adjoining Areas of Alzheimer’s Disease Patients,” Brain, Vol. 116, No. 1, 1993, pp. 103-115. doi:10.1093/brain/116.1.103
[151] J. W. Langston and L. S. Forno, “The Hypothalamus in Parkinson Disease,” Annals of Neurology, Vol. 3, No. 2, 1978, pp. 129-133. doi:10.1002/ana.410030207
[152] K. Otake, et al., “Hypothalamic Dysfunction in Parkinson’s Disease Patients,” Acta Medica Hungarica, Vol. 50, No. 1-2, 1994, pp. 3-13.
[153] E. Fabbrini, S. Sullivan and S. Klein, “Obesity and Nonalcoholic Fatty Liver Disease: Biochemical, Metabolic, and Clinical Implications,” Hepatology, Vol. 51, No. 2, 2010, pp. 679-689. doi:10.1002/hep.23280
[154] J. G. Langendonk, et al., “Circadian Rhythm of Plasma Leptin Levels in Upper and Lower Body Obese Women: Influence of Body Fat Distribution and Weight Loss,” The Journal of Clinical Endocrinology & Metabolism, Vol. 83, No. 5, 1998, pp. 1706-1712. doi:10.1210/jc.83.5.1706
[155] D. P. Figlewicz, “Adiposity Signals and Food Reward: Expanding the CNS Roles of Insulin and Leptin,” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 284, No. 4, 2003, pp. R882-R892.
[156] J. Harvey and M. L. Ashford, “Leptin in the CNS: Much More than a Satiety Signal,” Neuropharmacology, Vol. 44, No. 7, 2003, pp. 845-854. doi:10.1016/S0028-3908(03)00076-5
[157] S. P. Kalra, et al., “Rhythmic, Reciprocal Ghrelin and Leptin Signaling: New Insight in the Development of Obesity,” Regulatory Peptides, Vol. 111, No. 1-3, 2003, pp. 1-11. doi:10.1016/S0167-0115(02)00305-1
[158] M. D. Klok, S. Jakobsdottir and M. L. Drent, “The Role of Leptin and Ghrelin in the Regulation of Food Intake and Body Weight in Humans: A Review,” Obesity Reviews, Vol. 8, No. 1, 2007, pp. 21-34. doi:10.1111/j.1467-789X.2006.00270.x
[159] B. Bodosi, et al., “Rhythms of Ghrelin, Leptin, and Sleep in Rats: Effects of the Normal Diurnal Cycle, Restricted Feeding, and Sleep Deprivation,” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 287, No. 5, 2004, pp. R1071-R1079. doi:10.1152/ajpregu.00294.2004
[160] J. Sanchez, et al., “Diurnal Rhythms of Leptin and Ghrelin in the Systemic Circulation and in the Gastric Mucosa Are Related to Food Intake in Rats,” Pflügers Archiv, Vol. 448, No. 5, 2004, pp. 500-506. doi:10.1007/s00424-004-1283-4
[161] A. Kalsbeek, et al., “The Suprachiasmatic Nucleus Generates the Diurnal Changes in Plasma Leptin Levels,” Endocrinology, Vol. 142, No. 6, 2001, pp. 2677-2685. doi:10.1210/en.142.6.2677
[162] D. K. Oh, T. Ciaraldi and R. R. Henry, “Adiponectin in Health and Disease,” Diabetes, Obesity and Metabolism, Vol. 9, No. 3, 2007, pp. 282-289. doi:10.1111/j.1463-1326.2006.00610.x
[163] Y. Qi, et al., “Adiponectin Acts in the Brain to Decrease Body Weight,” Nature Medicine, Vol. 10, No. 5, 2004, pp. 524-529. doi:10.1038/nm1029
[164] S. Dridi and M. Taouis, “Adiponectin and Energy Homeostasis: Consensus and Controversy,” The Journal of Nutritional Biochemistry, Vol. 20, No. 11, 2009, pp. 831-839. doi:10.1016/j.jnutbio.2009.06.003
[165] J. Kawano and R. Arora, “The Role of Adiponectin in Obesity, Diabetes, and Cardiovascular Disease,” Journal of the CardioMetabolic Syndrome, Vol. 4, No. 1, 2009, pp. 44-49. doi:10.1111/j.1559-4572.2008.00030.x
[166] S. J. Chen, et al., “Relationships between Inflammation, Adiponectin, and Oxidative Stress in Metabolic Syndrome,” PLoS One, Vol. 7, No. 9, 2012, p. e45693. doi:10.1371/journal.pone.0045693
[167] J. P. Whitehead, et al., “Adiponectin—A Key Adipokine in the Metabolic Syndrome,” Diabetes, Obesity and Metabolism, Vol. 8, No. 3, 2006, pp. 264-280. doi:10.1111/j.1463-1326.2005.00510.x
[168] K. Rabe, et al., “Adipokines and Insulin Resistance,” Molecular Medicine, Vol. 14, No. 11-12, 2008, pp. 741-751. doi:10.2119/2008-00058.Rabe
[169] S. Yaturu, S. Prado and S. R. Grimes, “Changes in Adipocyte Hormones Leptin, Resistin, and Adiponectin in Thyroid Dysfunction,” Journal of Cellular Biochemistry, Vol. 93, No. 3, 2004, pp. 491-496. doi:10.1002/jcb.20188
[170] M. Barnea, Z. Madar and O. Froy, “High-Fat Diet Delays and Fasting Advances the Circadian Expression of Adiponectin Signaling Components in Mouse Liver,” Endocrinology, Vol. 150, No. 1, 2009, pp. 161-168. doi:10.1210/en.2008-0944
[171] E. Guillod-Maximin, et al., “Adiponectin Receptors Are Expressed in Hypothalamus and Colocalized with Proopiomelanocortin and Neuropeptide Y in Rodent Arcuate Neurons,” Journal of Endocrinology, Vol. 200, No. 1, 2009, pp. 93-105. doi:10.1677/JOE-08-0348
[172] J. Thundyil, et al., “Adiponectin receptor signalling in the brain,” British Journal of Pharmacology, Vol. 165, No. 2, 2012, pp. 313-327. doi:10.1111/j.1476-5381.2011.01560.x
[173] L. Qiao, et al., “Adiponectin Reduces Plasma Triglyceride by Increasing VLDL Triglyceride Catabolism,” Diabetes, Vol. 57, No. 7, 2008, pp. 1824-1833. doi:10.2337/db07-0435
[174] X. Wu, et al., “Involvement of AMP-Activated Protein Kinase in Glucose Uptake Stimulated by the Globular Domain of Adiponectin in Primary Rat Adipocytes,” Diabetes, Vol. 52, No. 6, 2003, pp. 1355-1363. doi:10.2337/diabetes.52.6.1355
[175] N. B. Ruderman, A. K. Saha and E. W. Kraegen, “Minireview: Malonyl CoA, AMP-Activated Protein Kinase, and Adiposity,” Endocrinology, Vol. 144, No. 12, 2003, pp. 5166-5171. doi:10.1210/en.2003-0849
[176] J. Karbowska and Z. Kochan, “Role of Adiponectin in the Regulation of Carbohydrate and Lipid Metabolism,” Journal of Physiology and Pharmacology, Vol. 57, Suppl. 6, 2006, pp. 103-113.
[177] L. Cantarini, et al., “Serum Leptin, Resistin, Visfatin and Adiponectin Levels in Tumor Necrosis Factor ReceptorAssociated Periodic Syndrome (TRAPS),” Clinical and Experimental Rheumatology, Vol. 30, No. 3, 2012, pp. S108-S114.
[178] T. M. van Himbergen, et al., “Biomarkers for Insulin Resistance and Inflammation and the Risk for All-Cause Dementia and Alzheimer Disease: Results from the Framingham Heart Study,” Archives of Neurology, Vol. 69, No. 5, 2012, pp. 594-600. doi:10.1001/archneurol.2011.670
[179] N. R. Cutler, “Neuropeptides in Alzheimer’s Disease: Somatostatin, Neuropeptide Y and Galanin,” American Journal of Alzheimer’s Care and Related Disorders and Reseacrh, Vol. 5, No. 1, 1990, pp. 7-12. doi:10.1177/153331759000500103
[180] H. Umegaki, “Neurodegeneration in Diabetes Mellitus,” Advances in Experimental Medicine and Biology, Vol. 724, 2012, pp. 258-265. doi:10.1007/978-1-4614-0653-2_19
[181] M. F. Beal, et al., “Neuropeptide Y Immunoreactivity Is Reduced in Cerebral Cortex in Alzheimer’s Disease,” Annals of Neurology, Vol. 20, No. 3, 1986, pp. 282-288. doi:10.1002/ana.410200303
[182] N. Croce, et al., “Neuropeptide Y Protects Rat Cortical Neurons against Beta-Amyloid Toxicity and Re-Establishes Synthesis and Release of Nerve Growth Factor,” ACS Chemical Neuroscience, Vol. 3, No. 4, 2012, pp. 312-318. doi:10.1021/cn200127e
[183] B. Beck, “Neuropeptide Y in Normal Eating and in Genetic and Dietary-Induced Obesity,” Philosophical Transactions of the Royal Society B Biological Science, Vol. 361, No. 1471, 2006, pp. 1159-1185. doi:10.1098/rstb.2006.1855
[184] M. Stachon, E. Furstenberg and J. Gromadzka-Ostrowska, “Effects of High-Fat Diets on Body Composition, Hypothalamus NPY, and Plasma Leptin and Corticosterone Levels in Rats,” Endocrine, Vol. 30, No. 1, 2006, pp. 69-74. doi:10.1385/ENDO:30:1:69
[185] H. Wang, L. H. Storlien and X. F. Huang, “Effects of Dietary Fat Types on Body Fatness, Leptin, and ARC Leptin Receptor, NPY, and AgRP mRNA Expression,” American Journal of Physiology-Endocrinology and Metabolism, Vol. 282, No. 6, 2002, pp. E1352-E1359.
[186] M. Heilig, “The NPY System in Stress, Anxiety and Depression,” Neuropeptides, Vol. 38, No. 4, 2004, pp. 213-224. doi:10.1016/j.npep.2004.05.002
[187] S. D. Primeaux, et al., “Effects of Altered Amygdalar Neuropeptide Y Expression on Anxiety-Related Behaviours,” Neuropsychopharmacology, Vol. 30, No. 9, 2005, pp. 1589-1597. doi:10.1038/sj.npp.1300705
[188] R. O. Tasan, et al., “The Central and Basolateral Amygdala Are Critical Sites of Neuropeptide Y/Y2 ReceptorMediated Regulation of Anxiety and Depression,” The Journal of Neuroscience, Vol. 30, No. 18, 2010, pp. 6282-6290. doi:10.1523/JNEUROSCI.0430-10.2010
[189] C. Veyrat-Durebex, et al., “Aging and Long-Term Caloric Restriction Regulate Neuropeptide Y Receptor Subtype Densities in the Rat Brain,” Neuropeptides, Vol. 47, No. 3, 2013, pp. 163-169. doi:10.1016/j.npep.2013.01.001
[190] M. I. Uusitupa, et al., “Neuropeptide Y: A Novel Link between the Neuroendocrine System and Cholesterol Metabolism,” Annals of Medicine, Vol. 30, No. 6, 1998, pp. 508-510. doi:10.3109/07853899809002597
[191] J. M. Rojas, et al., “Central Nervous System Neuropeptide Y Signaling via the Y1 Receptor Partially Dissociates Feeding Behavior from Lipoprotein Metabolism in Lean Rats,” American Journal of Physiology-Endocrinology and Metabolism, Vol. 303, No. 12, 2012, pp. E1479-E1488. doi:10.1152/ajpendo.00351.2012
[192] T. M. McShane, M. E. Wilson and P. M. Wise, “Effects of Lifelong Moderate Caloric Restriction on Levels of Neuropeptide Y, Proopiomelanocortin, and Galanin mRNA,” The Journals of Gerontology: Series A, Vol. 54, No. 1, 1999, pp. B14-B21. doi:10.1093/gerona/54.1.B14
[193] S. D. Primeaux, D. A. York and G. A. Bray, “Neuropeptide Y Administration into the Amygdala Alters High Fat Food Intake,” Peptides, Vol. 27, No. 7, 2006, pp. 1644-1651. doi:10.1016/j.peptides.2005.12.009
[194] M. Decressac and R. A. Barker, “Neuropeptide Y and Its Role in CNS Disease and Repair,” Experimental Neurology, Vol. 238, No. 2, 2012, pp. 265-272. doi:10.1016/j.expneurol.2012.09.004
[195] L. E. Kuo, et al., “Neuropeptide Y Acts Directly in the Periphery on Fat Tissue and Mediates Stress-Induced Obesity and Metabolic Syndrome,” Nature Medicine, Vol. 13, No. 7, 2007, pp. 803-811.
[196] R. D. Cone, “Anatomy and Regulation of the Central Melanocortin System,” Nature Neuroscience, Vol. 8, No. 5, 2005, pp. 571-578.
[197] G. Segal-Lieberman, et al., “Melanin-Concentrating Hormone Is a Critical Mediator of the Leptin-Deficient Phenotype,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 17, 2003, pp. 10085-10090. doi:10.1073/pnas.1633636100
[198] N. Balthasar, et al., “Divergence of Melanocortin Pathways in the Control of Food Intake and Energy Expenditure,” Cell, Vol. 123, No. 3, 2005, pp. 493-505. doi:10.1016/j.cell.2005.08.035
[199] S. Boghossian, M. Park and D. A. York, “Melanocortin Activity in the Amygdala Controls Appetite for Dietary Fat,” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 298, No. 2, 2010, pp. R385-R393. doi:10.1152/ajpregu.00591.2009
[200] S. Chung, et al., “Acute Homeostatic Responses to Increased Fat Consumption in MCH1R Knockout Mice,” Journal of Molecular Neuroscience, Vol. 42, No. 3, 2010, pp. 459-463. doi:10.1007/s12031-010-9358-5
[201] D. J. Marsh, et al., “Melanin-Concentrating Hormone 1 Receptor-Deficient Mice Are Lean, Hyperactive, and Hyperphagic and Have Altered Metabolism,” Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 5, 2002, pp. 3240-3245. doi:10.1073/pnas.052706899
[202] I. Morgansterna, G.-Q. Chang, O. Karatayeva and S. F Liebowitza, “Increased Orexin and Melanin-Concentrating Hormone Expression in the Perifornical Lateral Hypothalamus of Rats Prone to Overconsuming a FatRich Diet,” Pharmacology Biochemistry and Behavior, Vol. 96, No. 4, 2010, pp. 413-422. doi:10.1016/j.pbb.2010.06.013
[203] A. A. Butler, et al., “A Unique Metabolic Syndrome Causes Obesity in the Melanocortin-3 Receptor-Deficient Mouse,” Endocrinology, Vol. 141, No. 9, 2000, pp. 3518-3521. doi:10.1210/en.141.9.3518
[204] T. J. Kowalski and T. Sasikumar, “Melanin-Concentrating Hormone Receptor-1 Antagonists as Antiobesity Therapeutics: Current Status,” BioDrugs, Vol. 21, No. 5, 2007, pp. 311-321. doi:10.2165/00063030-200721050-00003
[205] S. C. Benoit, et al., “A Novel Selective Melanocortin-4 Receptor Agonist Reduces Food Intake in Rats and Mice without Producing Aversive Consequences,” Journal of Neuroscience, Vol. 20, No. 9, 2000, pp. 3442-3448.
[206] C. E. Perez-Leighton, et al., “Role of Orexin Receptors in Obesity: From Cellular to Behavioral Evidence,” International Journal of Obesity, Vol. 37, No. 2, 2013, pp. 167-174.
[207] C. Kotz, et al., “Brain Orexin Promotes Obesity Resistance,” Annals of the New York Academy of Sciences, Vol. 1264, No. 1, 2012, pp. 72-86. doi:10.1111/j.1749-6632.2012.06585.x
[208] E. Fride, “Endocannabinoids in the Central Nervous System—An Overview,” Prostaglandins, Leukotrienes and Essential Fatty Acids, Vol. 66, No. 2-3, 2002, pp. 221-233. doi:10.1054/plef.2001.0360
[209] T. Gomez Del Pulgar, et al., “Cannabinoids Protect Astrocytes from Ceramide-Induced Apoptosis through the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway,” The Journal of Biological Chemistry, Vol. 277, No. 39, 2002, pp. 36527-36533. doi:10.1074/jbc.M205797200
[210] G. Velasco, et al., “Cannabinoids and Ceramide: Two Lipids Acting Hand-by-Hand,” Life Sciences, Vol. 77, No. 14, 2005, pp. 1723-1731. doi:10.1016/j.lfs.2005.05.015
[211] V. Di Marzo, et al., “Leptin-Regulated Endocannabinoids Are Involved in Maintaining Food Intake,” Nature, Vol. 410, No. 6830, 2001, pp. 822-825.
[212] A. Mallat and S. Lotersztajn, “Cannabinoid Receptors as Novel Therapeutic Targets for the Management of Non-Alcoholic Steatohepatitis,” Diabetes & Metabolism, Vol. 34, No. 6, 2008, pp. 680-684. doi:10.1016/S1262-3636(08)74604-4
[213] D. H. Nam, et al., “Blockade of Cannabinoid Receptor 1 Improves Insulin Resistance, Lipid Metabolism, and Diabetic Nephropathy in db/db Mice,” Endocrinology, Vol. 153, No. 3, 2012, pp. 1387-1396. doi:10.1210/en.2011-1423
[214] Z. D. Thornton-Jones, et al., “The Cannabinoid CB1 Receptor Inverse Agonist, Rimonabant, Modifies Body Weight and Adiponectin Function in Diet-Induced Obese Rats as a Consequence of Reduced Food Intake,” Pharmacology Biochemistry and Behavior, Vol. 84, No. 2, 2006, pp. 353-359. doi:10.1016/j.pbb.2006.06.001
[215] S. Suzuki, et al., “Brain-Derived Neurotrophic Factor Regulates Cholesterol Metabolism for Synapse Development,” The Journal of Neuroscience, Vol. 27, No. 24, 2007, pp. 6417-6427. doi:10.1523/JNEUROSCI.0690-07.2007
[216] R. Molteni, et al., “A High-Fat, Refined Sugar Diet Reduces Hippocampal Brain-Derived Neurotrophic Factor, Neuronal Plasticity, and Learning,” Neuroscience, Vol. 112, No. 4, 2002, pp. 803-814. doi:10.1016/S0306-4522(02)00123-9
[217] V. De Chiara, et al., “Brain-Derived Neurotrophic Factor Controls Cannabinoid CB1 Receptor Function in the Striatum,” The Journal of Neuroscience, Vol. 30, No. 24, 2010, pp. 8127-8137. doi:10.1523/JNEUROSCI.1683-10.2010
[218] I. Tasci, H. K. Kabul and A. Aydogdu, “Brain Derived Neurotrophic Factor (BDNF) in Cardiometabolic Physiology and Diseases,” Anadolu Kardiyoloji Dergisi, Vol. 12, No. 8, 2012, pp. 684-688.
[219] M. Suwa, et al., “Serum Brain-Derived Neurotrophic Factor Level Is Increased and Associated with Obesity in Newly Diagnosed Female Patients with Type 2 Diabetes Mellitus,” Metabolism, Vol. 55, No. 7, 2006, pp. 852-857. doi:10.1016/j.metabol.2006.02.012
[220] H. Rosas-Vargas, J. D. Martinez-Ezquerro and T. Bienvenu, “Brain-Derived Neurotrophic Factor, Food Intake Regulation, and Obesity,” Archives of Medical Research, Vol. 42, No. 6, 2011, pp. 482-494. doi:10.1016/j.arcmed.2011.09.005
[221] M. Patterson, S. R. Bloom and J. V. Gardiner, “Ghrelin and Appetite Control in Humans—Potential Application in the Treatment of Obesity,” Peptides, Vol. 32, No. 11, 2011, pp. 2290-2294. doi:10.1016/j.peptides.2011.07.021
[222] B. Holst and T. W. Schwartz, “Constitutive Ghrelin Receptor Activity as a Signaling Set-Point in Appetite Regulation,” Trends in Pharmacological Sciences, Vol. 25, No. 3, 2004, pp. 113-117. doi:10.1016/j.tips.2004.01.010
[223] M. Scerif, A. P. Goldstone and M. Korbonits, “Ghrelin in Obesity and Endocrine Diseases,” Molecular and Cellular Endocrinology, Vol. 340, No. 1, 2011, pp. 15-25. doi:10.1016/j.mce.2011.02.011
[224] J. Gibbs, R. C. Young and G. P. Smith, “Cholecystokinin Decreases Food Intake in Rats,” Obesity Research, Vol. 5, No. 3, 1997, pp. 284-290. doi:10.1002/j.1550-8528.1997.tb00305.x
[225] T. J. Little, M. Horowitz and C. Feinle-Bisset, “Role of Cholecystokinin in Appetite Control and Body Weight Regulation,” Obesity Reviews, Vol. 6, No. 4, 2005, pp. 297-306. doi:10.1111/j.1467-789X.2005.00212.x
[226] L. M. Neff and R. F. Kushner, “Emerging Role of GLP-1 Receptor Agonists in the Treatment of Obesity,” Diabetes, Metabolic Syndrome and Obesity, Vol. 2010, 2010, pp. 263-273. doi:10.2147/DMSOTT.S6816
[227] J. J. Carlson, et al., “Preand Post-Prandial Appetite Hormone Levels in Normal Weight and Severely Obese Women,” Nutrition & Metabolism, Vol. 6, 2009, p. 32. doi:10.1186/1743-7075-6-32
[228] S. S. Torekov, S. Madsbad and J. J. Holst, “Obesity—An Indication for GLP-1 Treatment? Obesity Pathophysiology and GLP-1 Treatment Potential,” Obesity Reviews, Vol. 12, No. 8, 2011, pp. 593-601. doi:10.1111/j.1467-789X.2011.00860.x
[229] K. Wynne, B. C. Field and S. R. Bloom, “The Mechanism of Action for Oxyntomodulin in the Regulation of Obesity,” Current Opinion in Investigational Drugs, Vol. 11, No. 10, 2010, pp. 1151-1157.
[230] M. R. Druce and S. R. Bloom, “Oxyntomodulin: A Novel Potential Treatment for Obesity,” Treatments in Endocrinology, Vol. 5, No. 5, 2006, pp. 265-272.
[231] A. Asakawa, et al., “Characterization of the Effects of Pancreatic Polypeptide in the Regulation of Energy Balance,” Gastroenterology, Vol. 124, No. 5, 2003, pp. 1325-1336. doi:10.1016/S0016-5085(03)00216-6
[232] V. Lassmann, et al., “Low Plasma Levels of Pancreatic Polypeptide in Obesity,” Diabetes, Vol. 29, No. 6, 1980, pp. 428-430.
[233] D. Renshaw and R. L. Batterham, “Peptide YY: A Potential Therapy for Obesity,” Current Drug Targets, Vol. 6, No. 2, 2005, pp. 171-179. doi:10.2174/1389450053174523
[234] M. H. Tschop and E. Ravussin, “Peptide YY: Obesity’s Cause and Cure?” American Journal of Physiology-Endocrinology and Metabolism, Vol. 293, No. 5, 2007, pp. E1131-E1133. doi:10.1152/ajpendo.00568.2007
[235] K. Wada, et al., “Bombesin, Obesity, and Social Behaviour,” Molecular Psychiatry, Vol. 3, No. 3, 1998, pp. 204-206. doi:10.1038/sj.mp.4000387
[236] A. Amin, W. S. Dhillo and K. G. Murphy, “The Central Effects of Thyroid Hormones on Appetite,” Journal of Thyroid Research, Vol. 2011, 2011, Article ID: 306510.
[237] M. Pilhatsch, et al., “Hypothyroidism and Mood Disorders: Integrating Novel Insights from Brain Imaging Techniques,” Thyroid Research, Vol. 4, Suppl. 1, 2011, p. S3. doi:10.1186/1756-6614-4-S1-S3
[238] E. Cano-Europa, et al., “Hypothyroidism Induces Selective Oxidative Stress in Amygdala and Hippocampus of Rat,” Metabolic Brain Disease, Vol. 23, No. 3, 2008, pp. 275-287. doi:10.1007/s11011-008-9099-0
[239] C. J. Frederickson, et al., “Importance of Zinc in the Central Nervous System: The Zinc-Containing Neuron,” Journal of Nutrition, Vol. 130, Suppl. 5, 2000, pp. 1471S-1483S.
[240] N. Whittle, et al., “Rescue of Impaired Fear Extinction and Normalization of Cortico-Amygdala Circuit Dysfunction in a Genetic Mouse Model by Dietary Zinc Restriction,” The Journal of Neuroscience, Vol. 30, No. 41, 2010, pp. 13586-13596. doi:10.1523/JNEUROSCI.0849-10.2010
[241] A. Takeda, et al., “Increases in Extracellular Zinc in the Amygdala in Acquisition and Recall of Fear Experience and Their Roles in Response to Fear,” Neuroscience, Vol. 168, No. 3, 2010, pp. 715-722. doi:10.1016/j.neuroscience.2010.04.017
[242] R. Tudor, P. D. Zalewski and R. Ratnaike, “Zinc in Health and Chronic Disease,” The Journal of Nutrition Health and Aging, Vol. 9, No. 1, 2005, pp. 45-51.
[243] O. P. Garcia, K. Z. Long and J. L. Rosado, “Impact of Micronutrient Deficiencies on Obesity,” Nutrition Reviews, Vol. 67, No. 10, 2009, pp. 559-572. doi:10.1111/j.1753-4887.2009.00228.x
[244] J. Kim and S. Lee, “Effect of Zinc Supplementation on Insulin Resistance and Metabolic Risk Factors in Obese Korean Women,” Nutrition Research and Practice, Vol. 6, No. 3, 2012, pp. 221-225. doi:10.4162/nrp.2012.6.3.221
[245] C. W. Levenson, “Zinc Regulation of Food Intake: New Insights on the Role of Neuropeptide Y,” Nutrition Reviews, Vol. 61, No. 7, 2003, pp. 247-249.
[246] K. Ohinata, et al., “Orally Administered Zinc Increases Food Intake via Vagal Stimulation in Rats,” The Journal of Nutrition, Vol. 139, No. 3, 2009, pp. 611-616. doi:10.3945/jn.108.096370
[247] M. Foster and S. Samman, “Zinc and Regulation of Inflammatory Cytokines: Implications for Cardiometabolic Disease,” Nutrients, Vol. 4, No. 7, 2012, pp. 676-694. doi:10.3390/nu4070676
[248] M. Sowa-Kucma, et al., “Antidepressant-Like Activity of Zinc: Further Behavioral and Molecular Evidence,” Journal of Neural Transmission, Vol. 115, No. 12, 2008, pp. 1621-1628. doi:10.1007/s00702-008-0115-7
[249] C. S. Mantzoros, et al., “Zinc May Regulate Serum Leptin Concentrations in Humans,” Journal of the American College of Nutrition, Vol. 17, No. 3, 1998, pp. 270-275. doi:10.1080/07315724.1998.10718758
[250] E. S. Ott and N. F. Shay, “Zinc Deficiency Reduces Leptin Gene Expression and Leptin Secretion in Rat Adipocytes,” Experimental Biology and Medicine, Vol. 226, No. 9, 2001, pp. 841-846.
[251] D. B. Briggs, et al., “Zinc Enhances Adiponectin Oligomerization to Octadecamers but Decreases the Rate of Disulfide Bond Formation,” BioMetals, Vol. 25, No. 2, 2012, pp. 469-486. doi:10.1007/s10534-012-9519-9
[252] S. D. Soheilykhan, M. R. Mohammed, S. M. Mohammadi, M. Afkhami-Ardekani, S. A. Eghbali and F. Dehghan, “The Effect of Zinc Supplementation on Serum Adiponectin Concentration and Insulin Resistance in First Degree Relatives of Diabetic Patients,” Iranian Journal of Diabetes and Obesity, Vol. 4, No. 2, 2012, pp. 57-62.
[253] R. G. Lee, et al., “Zinc Deficiency Increases Hypothalamic Neuropeptide Y and Neuropeptide Y mRNA Levels and Does Not Block Neuropeptide Y-Induced Feeding in Rats,” The Journal of Nutrition, Vol. 128, No. 7, 1998, pp. 1218-1223.
[254] M. K. Hansen and T. M. Connolly, “Nuclear Receptors as Drug Targets in Obesity, Dyslipidemia and Atherosclerosis,” Current Opinion in Investigational Drugs, Vol. 9, No. 3, 2008, pp. 247-255.
[255] L. Guarente, “Sirtuins, Aging, and Metabolism,” Cold Spring Harbor Symposia on Quantitative Biology, Vol. 76, 2011, pp. 81-90. doi:10.1101/sqb.2011.76.010629
[256] C. Harrison, “Neurodegenerative Disorders: A Neuroprotective Role for Sirtuin 1,” Nature Reviews Drug Discovery, Vol. 11, 2012, p. 108.
[257] T. Kawada, et al., “Dietary Regulation of Nuclear Receptors in Obesity-Related Metabolic Syndrome,” Asia Pacific Journal of Clinical Nutrition, Vol. 17, Suppl. 1, 2008, pp. 126-130.
[258] H. I. Swanson, et al., “Role of Nuclear Receptors in Lipid Dysfunction and Obesity-Related Diseases,” Drug Metabolism & Disposition, Vol. 41, No. 1, 2013, pp. 1-11. doi:10.1124/dmd.112.048694
[259] I. Cakir, et al., “Hypothalamic Sirt1 Regulates Food Intake in a Rodent Model System,” PLoS One, Vol. 4, No. 12, 2009, p. e8322. doi:10.1371/journal.pone.0008322
[260] T. Kitamura and T. Sasaki, “Hypothalamic Sirt1 and Regualtion of Food Intake,” Diabetology International, Vol. 3, No. 3, 2012, pp. 109-112. doi:10.1007/s13340-012-0088-5
[261] M. O. Dietrich, et al., “Agrp Neurons Mediate Sirt1’s Action on the Melanocortin System and Energy Balance: roles for Sirt1 in Neuronal Firing and Synaptic Plasticity,” The Journal of Neuroscience, Vol. 30, No. 35, 2010, pp. 11815-11825. doi:10.1523/JNEUROSCI.2234-10.2010
[262] A. O. Schaffhauser, et al., “Effects of a High-Fat Diet and Strain on Hypothalamic Gene Expression in Rats,” Obesity Research, Vol. 10, No. 11, 2002, pp. 1188-1196. doi:10.1038/oby.2002.161
[263] A. K. Lee, et al., “Effect of High-Fat Feeding on Expression of Genes Controlling Availability of Dopamine in Mouse Hypothalamus,” Nutrition, Vol. 26, No. 4, 2010, pp. 411-422. doi:10.1016/j.nut.2009.05.007
[264] D. E. Cohen, et al., “Neuronal SIRT1 Regulates Endocrine and Behavioral Responses to Calorie Restriction,” Genes & Development, Vol. 23, No. 24, 2009, pp. 2812-2817. doi:10.1101/gad.1839209
[265] A. Takano, et al., “Growth Hormone Induces Cellular Insulin Resistance by Uncoupling Phosphatidylinositol 3-Kinase and Its Downstream Signals in 3T3-L1 Adipocytes,” Diabetes, Vol. 50, No. 8, 2001, pp. 1891-1900. doi:10.2337/diabetes.50.8.1891
[266] M. Kitada, et al., “Sirtuins and Renal Diseases: Relationship with Aging and Diabetic Nephropathy,” Clinical Science, Vol. 124, No. 3, 2013, pp. 153-164. doi:10.1042/CS20120190
[267] S. Rajendrasozhan, et al., “SIRT1, an Antiinflammatory and Antiaging Protein, Is Decreased in Lungs of Patients with Chronic Obstructive Pulmonary Disease,” American Journal of Respiratory and Critical Care Medicine, Vol. 177, No. 8, 2008, pp. 861-870. doi:10.1164/rccm.200708-1269OC
[268] J. R. Archer and E. H. Baker, “Diabetes and Metabolic Dysfunction in COPD,” Respiratory Medicine, Vol. 5, No. 3-4, 2009, pp. 67-74.
[269] A. Planavila, et al., “Sirt1 Acts in Association with PPARalpha to Protect the Heart from Hypertrophy, Metabolic Dysregulation, and Inflammation,” Cardiovascular Research, Vol. 90, No. 2, 2011, pp. 276-284. doi:10.1093/cvr/cvq376
[270] S. Oka, et al., “PPARalpha-Sirt1 Complex Mediates Cardiac Hypertrophy and Failure through Suppression of the ERR Transcriptional Pathway,” Cell Metabolism, Vol. 14, No. 5, 2011, pp. 598-611. doi:10.1016/j.cmet.2011.10.001
[271] F. M. Campbell, et al., “A Role for Peroxisome Proliferator-Activated Receptor Alpha (PPARalpha) in the Control of Cardiac Malonyl-CoA Levels: Reduced Fatty Acid Oxidation Rates and Increased Glucose Oxidation Rates in the Hearts of Mice Lacking PPARalpha Are Associated with Higher Concentrations of Malonyl-CoA and Reduced Expression of Malonyl-CoA Decarboxylase,” The Journal of Biological Chemistry, Vol. 277, No. 6, 2002, pp. 4098-4103. doi:10.1074/jbc.M106054200
[272] R. J. Rodgers, M. H. Tschop and J. P. Wilding, “AntiObesity Drugs: Past, Present and Future,” Disease Models & Mechanisms, Vol. 5, No. 5, 2012, pp. 621-626. doi:10.1242/dmm.009621
[273] V. Hainer and I. A. Hainerova, “Do We Need Anti-Obesity Drugs?” Diabetes/Metabolism Research and Reviews, Vol. 28, Suppl. 2, 2012, pp. 8-20. doi:10.1002/dmrr.2349
[274] D. J. Heal, J. Gosden and S. L. Smith, “What Is the Prognosis for New Centrally-Acting Anti-Obesity Drugs?” Neuropharmacology, Vol. 63, No. 1, 2012, pp. 132-146. doi:10.1016/j.neuropharm.2012.01.017
[275] G. Derosa and P. Maffioli, “Anti-Obesity Drugs: A Review about Their Effects and Their Safety,” Expert Opinion on Drug Safety, Vol. 11, No. 3, 2012, pp. 459-471. doi:10.1517/14740338.2012.675326
[276] M. F. Li and B. M. Cheung, “Rise and Fall of Anti-Obesity Drugs,” World Journal of Diabetes, Vol. 2, No. 2, 2011, pp. 19-23. doi:10.4239/wjd.v2.i2.19
[277] E. Yulyaningsih, et al., “NPY Receptors as Potential Targets for Anti-Obesity Drug Development,” British Journal of Pharmacology, Vol. 163, No. 6, 2011, pp. 1170-1202. doi:10.1111/j.1476-5381.2011.01363.x
[278] T. M. Fong, “Development of Anti-Obesity Agents: Drugs that Target Neuropeptide and Neurotransmitter Systems,” Expert Opinion on Investigational Drugs, Vol. 17, No. 3, 2008, pp. 321-325. doi:10.1517/13543784.17.3.321
[279] S. Thakran, et al., “Role of Sirtuin 1 in the Regulation of Hepatic Gene Expression by Thyroid Hormone,” The Journal of Biological Chemistry, Vol. 288, No. 2, 2013, pp. 807-818. doi:10.1074/jbc.M112.437970

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.