Leptin Causes the Early Inhibition of Glycolysis- and TCA Cycle-Related Genes in the Brain of Ob/Ob Mice to Restore Fertility ()
ABSTRACT
Introduction: Polycystic
ovarian syndrome (PCOS) is undoubtedly the commonest androgen disorder in
woman’s fertile period and certainly one of the most prevalent causes of
anovulation. The syndrome has an estimated prevalence of 4% - 10% among women
of childbearing age. Previously, our group demonstrated the effect of gonadal
white adipose tissue transplantation from wild-type lean and fertile female
mice to isogenic obese anovulatory ob/ob mice. These complex metabolic
interrelationships between obesity and PCOS have yet to be fully understood.
The aim of this study was to evaluate the effect of gonadal white adipose
tissue (WAT) transplantation from the wild-type lean and fertile female mice to
isogenic obese, anovulatory mice (Lep ob/Lep ob) on the expression of
glycolysis- and TCA cycle-related genes and obtain a general view of the
glucose metabolism in the brain of these animals. Methods: Fifteen ob/ob mice
ranging from 2 to 3 months of age were divided into 3 experimental groups:
control normal weight (n = 5), obese control (n = 5) and obese 7 days leptin
treated (n = 5). The whole brains of the mice were processed for RNA
extraction. The samples from each group were used to perform PCR assays using
an array plate containing 84 primers to study the glucose metabolism-related
genes. Results: The glycolysis- and TCA cycle-related genes were significantly downregulated.
The most significantly affected genes were as follows: for glycolysis (fold
regulation with p < 0.05):Pgm1,Bpgm,Aldob, andEno3 (119, 45,
18, and 28 times less, respectively); and for the TCA cycle (fold regulation
with p < 0.05):Cs,Idh3b,
andMdh2 (84, 27, and 37 times less,
respectively).Conclusion: The seven-day
leptin treated mice show a decrease in the glucose metabolism. These results
confirm the ability of the adipose tissue-derived hormone leptin to regulate
early crucial genes that are related to glycolysis mechanisms and to the TCA
cycle. This hormone seems to revert early the central physiological conditions
that are associated with PCOS; however, the morphological alterations can only
be observed within a 45-day treatment.
Share and Cite:
Baptista, C. , Noronha, S. , Ritto, M. , Freitas, E. , Júnior, M. , Haidar, M. , Silva, I. , Noronha, S. and Patriarca, M. (2014) Leptin Causes the Early Inhibition of Glycolysis- and TCA Cycle-Related Genes in the Brain of Ob/Ob Mice to Restore Fertility.
American Journal of Molecular Biology,
4, 105-113. doi:
10.4236/ajmb.2014.43012.
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