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Updated: May 15, 2026

Mechanism of Regulation of Adipocyte Numbers in Adult Organisms Through Differentiation and Apoptosis Homeostasis
Published on: June 3, 2016
Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein
Jingbo Yan1, Fang C Mei, Hongqiang Cheng
1Department of Pharmacology and Toxicology, Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch, Galveston, Texas, USA.
Abstract:
The prototypic second messenger cyclic AMP (cAMP) is essential for controlling cellular metabolism, including glucose and lipid homeostasis. In mammals, the majority of cAMP functions are mediated by cAMP-dependent protein kinase (PKA) and exchange proteins directly activated by cAMP (Epacs). To explore the physiological functions of Epac1, we generated Epac1 knockout mice. Here we report that Epac1 null mutants have reduced white adipose tissue and reduced plasma leptin levels but display heightened leptin sensitivity. Epac1-deficient mice are more resistant to high-fat diet-induced obesity, hyperleptinemia, and glucose intolerance. Furthermore, pharmacological inhibition of Epac by use of an Epac-specific inhibitor reduces plasma leptin levels in vivo and enhances leptin signaling in organotypic hypothalamic slices. Taken together, our results demonstrate that Epac1 plays an important role in regulating adiposity and energy balance.
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