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Overexpression of Constitutively Active PKG-I Protects Female, But Not Male Mice From Diet-Induced Obesity.
MedLine Citation:
PMID:  20930715     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Cyclic guanosine monophosphate (cGMP)-dependent protein kinase I (PKG-I) is a multifunctional protein. The direct effects of PKG-I activation on energy homeostasis and obesity development are not well understood. Herein, we generated transgenic mice with expression of the constitutively active PKG-I in adipose tissue as well as in other tissues. Male and female PKG-I overexpressing mice were fed a low-fat (LF) or high-fat (HF) diet for 16 weeks. HF-fed female PKG-I transgenic mice had decreased body weight gain, lower percentage of body fat, and improved glucose tolerance compared to HF-fed wild-type (WT) controls. In contrast, male transgenic PKG-I mice were not resistant to the development of HF-diet-induced obesity, and exhibited similar levels of adiposity and glucose intolerance as HF-fed WT controls. Furthermore, we found that HF-fed female transgenic PKG-I mice had increased energy expenditure and cold-induced adaptive thermogenesis compared to HF-fed WT controls, which was associated with increased expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT). In addition, the rates of lipolysis in white adipose tissue (WAT) were also increased in female transgenic PKG-I mice compared to WT controls due to increased phosphorylation of hormone-sensitive lipase (HSL). However, in male mice, adaptive thermogenesis or WAT lipolysis was similar between transgenic PKG-I mice and WT controls. Together, these data demonstrate sex differences in effects of PKG-I activation on the regulation of adipose tissue function and its contribution to diet induced obesity.
Authors:
Dejan M Nikolic; Yanzhang Li; Shu Liu; Shuxia Wang
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Publication Detail:
Type:  Journal Article     Date:  2010-10-07
Journal Detail:
Title:  Obesity (Silver Spring, Md.)     Volume:  19     ISSN:  1930-7381     ISO Abbreviation:  Obesity (Silver Spring)     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101264860     Medline TA:  Obesity (Silver Spring)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  784-91     Citation Subset:  IM    
Affiliation:
Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky, USA.
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