Adenylyl cyclase 3 haploinsufficiency confers susceptibility to diet-induced obesity and insulin resistance in mice

Adenylyl cyclase 3 (Adcy3 ), a member of the mammalian adenylyl cyclase family responsible for generating the second messenger cAMP, has long been known to play an essential role in olfactory signal transduction. Here, we demonstrated that Adcy3 heterozygous null mice displayed increased visceral ad...

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Bibliographic Details
Published in:Scientific reports 2016-09, Vol.6 (1), p.34179-34179, Article 34179
Main Authors: Tong, Tao, Shen, Ying, Lee, Han-Woong, Yu, Rina, Park, Taesun
Format: Article
Language:English
Subjects:
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Adipogenesis
Adipose tissue
Animal tissues
Cyclic AMP
Cytokines
Dyslipidemia
Haploinsufficiency
High fat diet
Humanities and Social Sciences
Hyperphagia
Inflammation
Insulin
Insulin resistance
Liver
multidisciplinary
Obesity
Oxidation
Plasma levels
Rodents
Science
Signal transduction
Thermogenesis
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Summary:Adenylyl cyclase 3 (Adcy3 ), a member of the mammalian adenylyl cyclase family responsible for generating the second messenger cAMP, has long been known to play an essential role in olfactory signal transduction. Here, we demonstrated that Adcy3 heterozygous null mice displayed increased visceral adiposity in the absence of hyperphagia and developed abnormal metabolic features characterized by impaired insulin sensitivity, dyslipidemia and increased plasma levels of proinflammatory cytokines on both chow and high-fat diet (HFD). Of note, HFD decreased the Adcy3 expression in white adipose tissue, liver and muscle. We also report for the first time that Adcy3 haploinsufficiency resulted in reduced expression of genes involved in thermogenesis, fatty acid oxidation and insulin signaling, with enhanced expression of genes related to adipogenesis in peripheral tissues of mice. In conclusion, these findings suggest that cAMP signals generated by Adcy3 in peripheral tissues may play a pivotal role in modulating obesity and insulin sensitivity.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep34179