title: Inactivation of PKCtheta leads to increased susceptibility to obesity and dietary insulin resistance in mice.
abstract: 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.
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA. yej@pbrc.edu
authors.forename: Zhanguo
authors.initials: Z
authors.lastname: Gao
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Butler
authors.forename: Aamir
authors.initials: A
authors.lastname: Zuberi
authors.forename: Barbara
authors.initials: B
authors.lastname: Gawronska-Kozak
authors.forename: Michael
authors.initials: M
authors.lastname: Lefevre
authors.forename: David
authors.initials: D
authors.lastname: York
authors.forename: Eric
authors.initials: E
authors.lastname: Ravussin
authors.forename: Hans-Rudolf
authors.initials: HR
authors.lastname: Berthoud
authors.forename: Owen
authors.initials: O
authors.lastname: McGuinness
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Jianping
authors.initials: J
authors.lastname: Ye
mesh_terms: 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
chemical_list: D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007527:Isoenzymes; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D005947:Glucose