Overexpression of constitutively active PKG-I protects female, but not male mice from diet-induced obesity.

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.

• Authors: Dejan M Nikolic, Yanzhang Li, Shu Liu, Shuxia Wang
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 19 Issue 4 Pg. 784-91 (Apr 2011) ISSN: 1930-739X [Electronic] United States
• PMID: 20930715 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Dietary Fats
• Ion Channels
• Mitochondrial Proteins
• Ucp1 protein, mouse
• Uncoupling Protein 1
• Cyclic GMP-Dependent Protein Kinases
• Sterol Esterase

Topics

• Adipose Tissue, Brown (metabolism)
• Adipose Tissue, White (metabolism)
• Adiposity
• Analysis of Variance
• Animals
• Body Composition
• Body Weight
• Cyclic GMP-Dependent Protein Kinases (genetics, metabolism)
• Diet
• Dietary Fats (administration & dosage)
• Eating
• Energy Metabolism
• Female
• Glucose Tolerance Test
• Ion Channels (metabolism)
• Lipolysis
• Male
• Mice
• Mice, Transgenic
• Mitochondrial Proteins (metabolism)
• Obesity (chemically induced)
• Sex Factors
• Sterol Esterase (metabolism)
• Thermogenesis
• Uncoupling Protein 1