Protein kinase Cβ deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling.
To explore the role of leptin in PKCβ action and to determine the protective potential of PKCβ deficiency on profound obesity, double knockout (DBKO) mice lacking PKCβ and ob genes were created, and key parameters of metabolism and body composition were studied. DBKO mice had similar caloric intake as ob/ob mice but showed significantly reduced body fat content, improved glucose metabolism, and elevated body temperature. DBKO mice were resistant to high-fat diet-induced obesity. Moreover, PKCβ deficiency increased β-adrenergic signaling by inducing expression of β1- and β3-adrenergic receptors (β-ARs) in white adipose tissue (WAT) of ob/ob mice. Accordingly, p38(MAPK) activation and expression of PGC-1α and UCP-1 were increased in WAT of DBKO mice. Consistent with results of in vivo studies, inhibition of PKCβ in WAT explants from ob/ob mice also increased expression of above β-ARs. In contrast, induction of PGC-1α and UCP-1 expression in brown adipose tissue of DBKO mice was not accompanied by changes in the expression of these β-ARs. Collectively, these findings suggest that PKCβ deficiency may prevent genetic obesity, in part, by remodeling the catabolic function of adipose tissues through β-ARs dependent and independent mechanisms.
Department of Molecular & Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210.
Wei
W
Huang
Department of Molecular & Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210.
Rishipal R
RR
Bansode
Department of Physiology, The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210 and.
Naresh C
NC
Bal
Department of Medicine, The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210.
Madhu
M
Mehta
Department of Molecular & Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute,The Ohio State University College of Medicine, 1645 Neil Avenue, Columbus, OH 43210. Electronic address: Mehta.80@osu.edu.
Kamal D
KD
Mehta
D002001:Adipose Tissue, Brown / Q000378:metabolism; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D059305:Diet, High-Fat / Q000009:adverse effects; D004435:Eating / Q000235:genetics / Q000502:physiology; D005838:Genotype; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption / Q000235:genetics / Q000502:physiology; D011493:Protein Kinase C / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism; D022722:Thermogenesis / Q000235:genetics / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D014280:Triglycerides; D011493:Protein Kinase C; D064546:Protein Kinase C beta