Premium
Overexpression of Constitutively Active PKG‐I Protects Female, But Not Male Mice From Diet‐Induced Obesity
Author(s) -
Nikolic Dejan M.,
Li Yanzhang,
Liu Shu,
Wang Shuxia
Publication year - 2011
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2010.223
Subject(s) - medicine , endocrinology , thermogenesis , brown adipose tissue , adipose tissue , white adipose tissue , lipolysis , genetically modified mouse , cgmp dependent protein kinase , protein kinase a , transgene , cyclic guanosine monophosphate , energy homeostasis , biology , thermogenin , chemistry , kinase , obesity , nitric oxide , microbiology and biotechnology , biochemistry , gene , cyclin dependent kinase 2
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.