title: Loss of protein kinase Cbeta function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance.
abstract: Obesity is an energy balance disorder in which intake is greater than expenditure, with most excess calories stored as triglyceride (TG). We previously reported that mice lacking the beta-isoform of protein kinase C (PKCbeta), a diacylglycerol- and phospholipid-dependent kinase, exhibit marked reduction in the whole body TG content, including white adipose tissue (WAT) mass. To investigate the role of this signaling kinase in metabolic adaptations to severe dietary stress, we studied the impact of a high-fat diet (HFD) on PKCbeta expression and the effect of PKCbeta deficiency on profound weight gain. We report herein that HFD selectively increased PKCbeta expression in obesity-prone C57BL/6J mice, specifically in WAT; the expression levels were little or unchanged in the liver, muscle, kidney, and heart. Basal PKCbeta expression was also found to be elevated in WAT of obese ob/ob mice. Remarkably, mice lacking PKCbeta were resistant to HFD-induced obesity, showing significantly reduced WAT and slightly higher core body temperatures. Unlike lean lipodystrophic mouse models, these mice did not have fatty livers, nor did they exhibit insulin resistance. Moreover, PKCbeta(-/-) mice exhibited changes in lipid metabolism gene expression, and such alterations were accompanied by significant changes in serum adipokines. These observations suggest that PKCbeta deficiency induced a unique metabolic state congruous with obesity resistance, thus raising the possibility that dysregulation of PKCbeta expression could contribute to dietary fat-induced obesity and related disorders.
authors.affiliation: Department of Molecular and Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Rishipal
authors.initials: R
authors.lastname: Bansode
authors.forename: Madhu
authors.initials: M
authors.lastname: Mehta
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Mehta
mesh_terms: D054392:Adipokines / Q000097:blood; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D005227:Fatty Acids / Q000096:biosynthesis; D005234:Fatty Liver / Q000209:etiology; D015870:Gene Expression; D007333:Insulin Resistance; D007527:Isoenzymes / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011493:Protein Kinase C / Q000172:deficiency / Q000378:metabolism*; D064546:Protein Kinase C beta
chemical_list: D054392:Adipokines; D004041:Dietary Fats; D005227:Fatty Acids; D007527:Isoenzymes; D011493:Protein Kinase C; D064546:Protein Kinase C beta