Inactivation of PKCtheta leads to increased susceptibility to obesity and dietary insulin resistance in mice.
In this study, we investigated the metabolic phenotype of PKCtheta knockout mice (C57BL/6J) on chow diet and high-fat diet (HFD). The knockout (KO) mice are normal in growth and reproduction. On the chow diet, body weight and food intake were not changed in the KO mice; however, body fat content was increased with a corresponding decrease in body lean mass. Energy expenditure and spontaneous physical activity were decreased in the KO mice. On HFD, energy expenditure and physical activity remained low in the KO mice. The body weight and fat content were increased rapidly in the KO mice. At 8 wk on HFD, severe insulin resistance was detected in the KO mice with hyperinsulinemic euglycemic clamp and insulin tolerance test. Insulin action in both hepatic and peripheral tissues was reduced in the KO mice. Plamsa free fatty acid was increased, and expression of adiponectin in the adipose tissue was decreased, in the KO mice on HFD. This study suggests that loss of PKCtheta reduces energy expenditure and increases the risk of dietary obesity and insulin resistance in mice.
Gao
Zhanguo
Z
Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA. yej@pbrc.edu
Wang
Zhong
Z
Zhang
Xiaoying
X
Butler
Andrew A
AA
Zuberi
Aamir
A
Gawronska-Kozak
Barbara
B
Lefevre
Michael
M
York
David
D
Ravussin
Eric
E
Berthoud
Hans-Rudolf
HR
McGuinness
Owen
O
Cefalu
William T
WT
Ye
Jianping
J
D052242:Adiponectin / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000818:Animals; D004036:Diet, Atherogenic; D005230:Fatty Acids, Nonesterified / Q000097:blood; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000096:biosynthesis / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000235:genetics*; D011493:Protein Kinase C / Q000235:genetics*; D000074121:Protein Kinase C-theta
D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D005947:Glucose