Protein kinase C deficiency increases fatty acid oxidation and reduces fat storage.
Metabolic syndrome is common in the general population, but there is little information available on the underlying signaling mechanisms regulating triglyceride (TG) content in the body. In the current study, we have uncovered a role for protein kinase Cbeta (PKCbeta) in TG homeostasis by studying the consequences of a targeted disruption of this kinase. PKCbeta(-/-) mutant mice were considerably leaner and the size of white fat depots was markedly decreased compared with wild-type littermates. TG content in the liver and skeletal muscle of PKCbeta(-/-) mice was also significantly low. Interestingly, mutant animals were hyperphagic and exhibited higher food intake and reduced feed efficiency versus wild type. The protection from obesity involves elevated oxygen consumption/energy expenditure and increased fatty acid oxidation in adipose tissue with concurrent increased mitochondria genesis, up-regulation of PGC-1alpha and UCP-2, and down-regulation of perilipin. The ability of PKCbeta deficiency to promote fat burning in adipocytes may suggest novel therapeutic strategies for obesity and obesity-related disorders.
Bansode
Rishipal R
RR
Department of Molecular and Cellular Biochemistry, Columbus, Ohio 43210.
Huang
Wei
W
Department of Molecular and Cellular Biochemistry, Columbus, Ohio 43210.
Roy
Sanjit K
SK
Department of Molecular and Cellular Biochemistry, Columbus, Ohio 43210.
Mehta
Madhu
M
Department of Medicine, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio 43210.
Mehta
Kamal D
KD
Department of Molecular and Cellular Biochemistry, Columbus, Ohio 43210. Electronic address: Mehta.80@osu.edu.
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D000273:Adipose Tissue / Q000378:metabolism / Q000648:ultrastructure; D050154:Adiposity; D000818:Animals; D001835:Body Weight; D002245:Carbon Dioxide / Q000378:metabolism; D005223:Fats / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism; D019301:Oleic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption; D011493:Protein Kinase C / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D014280:Triglycerides / Q000378:metabolism
D005223:Fats; D005227:Fatty Acids; D020738:Leptin; D014280:Triglycerides; D002245:Carbon Dioxide; D019301:Oleic Acid; D011493:Protein Kinase C; D064546:Protein Kinase C beta