Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP Isoform 1

Jingbo Yan, Fang C. Mei, Hongqiang Cheng, Dieu Hung Lao, Yaohua Hu, Jingna Wei, Igor Patrikeev, Dapeng Hao, Sonja J. Stutz, Kelly Dineley, Massoud Motamedi, Jonathan Hommel, Kathryn Cunningham, Ju Chen, Xiaodong Cheng

Research output: Contribution to journalArticle

47 Citations (Scopus)

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-specificinhibitor 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.

Original languageEnglish (US)
Pages (from-to)918-926
Number of pages9
JournalMolecular and Cellular Biology
Volume33
Issue number5
DOIs
StatePublished - Mar 2013

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Adiposity
Leptin
Cyclic AMP
Protein Isoforms
Homeostasis
Glucose
Proteins
White Adipose Tissue
Glucose Intolerance
High Fat Diet
Second Messenger Systems
Cyclic AMP-Dependent Protein Kinases
Knockout Mice
Mammals
Obesity
Pharmacology
Lipids

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP Isoform 1. / Yan, Jingbo; Mei, Fang C.; Cheng, Hongqiang; Lao, Dieu Hung; Hu, Yaohua; Wei, Jingna; Patrikeev, Igor; Hao, Dapeng; Stutz, Sonja J.; Dineley, Kelly; Motamedi, Massoud; Hommel, Jonathan; Cunningham, Kathryn; Chen, Ju; Cheng, Xiaodong.

In: Molecular and Cellular Biology, Vol. 33, No. 5, 03.2013, p. 918-926.

Research output: Contribution to journalArticle

Yan, Jingbo ; Mei, Fang C. ; Cheng, Hongqiang ; Lao, Dieu Hung ; Hu, Yaohua ; Wei, Jingna ; Patrikeev, Igor ; Hao, Dapeng ; Stutz, Sonja J. ; Dineley, Kelly ; Motamedi, Massoud ; Hommel, Jonathan ; Cunningham, Kathryn ; Chen, Ju ; Cheng, Xiaodong. / Enhanced leptin sensitivity, reduced adiposity, and improved glucose homeostasis in mice lacking exchange protein directly activated by cyclic AMP Isoform 1. In: Molecular and Cellular Biology. 2013 ; Vol. 33, No. 5. pp. 918-926.
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