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Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP isoform 1.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2013 Mar; Vol. 33 (5), pp. 918-26. Date of Electronic Publication: 2012 Dec 21. - Publication Year :
- 2013
-
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.
- Subjects :
- Adipose Tissue, White metabolism
Animals
Diet, High-Fat adverse effects
Gene Knockout Techniques
Glucose Tolerance Test
Leptin blood
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity etiology
Obesity genetics
Signal Transduction
Weight Gain
Adiposity genetics
Cyclic AMP metabolism
Glucose metabolism
Guanine Nucleotide Exchange Factors genetics
Leptin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 33
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 23263987
- Full Text :
- https://doi.org/10.1128/MCB.01227-12