Role of exchange protein directly activated by cyclic AMP isoform 1 in energy homeostasis: Regulation of leptin expression and secretion in white adipose tissue

Yaohua Hu, William G. Robichaux, Fang C. Mei, Eun Ran Kim, Hui Wang, Qingchun Tong, Jianping Jin, Mingxuan Xu, Ju Chen, Xiaodong Cheng

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Epacs (exchange proteins directly activated by cyclic AMP [cAMP]) act as downstream effectors of cAMP and play important roles in energy balance and glucose homeostasis. While global deletion of Epac1 in mice leads to heightened leptin sensitivity in the hypothalamus and partial protection against high-fat diet (HFD)-induced obesity, the physiological functions of Epac1 in white adipose tissue (WAT) has not been explored. Here, we report that adipose tissue-specific Epac1 knockout (AEKO) mice are more prone to HFD-induced obesity, with increased food intake, reduced energy expenditure, and impaired glucose tolerance. Despite the fact that AEKO mice on HFD display increased body weight, these mice have decreased circulating leptin levels compared to their wild-type littermates. In vivo and in vitro analyses further reveal that suppression of Epac1 in WAT decreases leptin mRNA expression and secretion by inhibiting cAMP response element binding (CREB) protein and AKT phosphorylation, respectively. Taken together, our results demonstrate that Epac1 plays an important role in regulating energy balance and glucose homeostasis by promoting leptin expression and secretion in WAT.

Original languageEnglish (US)
Pages (from-to)2440-2450
Number of pages11
JournalMolecular and cellular biology
Volume36
Issue number19
DOIs
StatePublished - 2016
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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