The first three authors contributed equally to this work.
Overexpression of Constitutively Active PKG-I Protects Female, But Not Male Mice From Diet-Induced Obesity
Article first published online: 6 SEP 2012
2011 North American Association for the Study of Obesity (NAASO)
Volume 19, Issue 4, pages 784–791, April 2011
How to Cite
Nikolic, D. M., Li, Y., Liu, S. and Wang, S. (2011), Overexpression of Constitutively Active PKG-I Protects Female, But Not Male Mice From Diet-Induced Obesity. Obesity, 19: 784–791. doi: 10.1038/oby.2010.223
- Issue published online: 6 SEP 2012
- Article first published online: 6 SEP 2012
- Received 15 July 2009; accepted 25 July 2010
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.