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- Title
Overexpression of Constitutively Active PKG-I Protects Female, But Not Male Mice From Diet-Induced Obesity.
- Authors
Nikolic, Dejan M.; Li, Yanzhang; Liu, Shu; Wang, Shuxia
- Abstract
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.
- Subjects
PROTEIN kinases; CYCLIC guanylic acid; DIET in disease; OBESITY; MICE
- Publication
Obesity (19307381), 2011, Vol 19, Issue 4, p784
- ISSN
1930-7381
- Publication type
Article
- DOI
10.1038/oby.2010.223