Protein kinase Cβ deficiency attenuates obesity syndrome of ob/ob mice by promoting white adipose tissue remodeling

Wei Huang,Naresh C Bal,Madhu Mehta,Kamal D Mehta,Rishipal R Bansode

doi:10.1194/jlr.m019687

Abstract

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.

Highlights

To explore the role of leptin in protein kinase C (PKC)␤ action and to determine the protective potential of PKC␤ deficiency on profound obesity, double knockout (DBKO) mice lacking PKC␤ and ob genes were created, and key parameters of metabolism and body composition were studied
Our findings show that PKC␤ deficiency in ob/ob mice produces an integrated series of molecular, cellular, and physiological responses that have a profound impact on energy expenditure without affecting the energy intake component of the energy balance equation
The net effect of these responses is a decrease in metabolic efficiency and a corresponding decrease in fat accretion in adipose tissue of DBKO mice compared with ob/ob mice

Summary

Introduction

To explore the role of leptin in PKC␤ action and to determine the protective potential of PKC␤ deficiency on profound obesity, double knockout (DBKO) mice lacking PKC␤ and ob genes were created, and key parameters of metabolism and body composition were studied. PKC␤ deficiency increased ␤-adrenergic signaling by inducing expression of ␤1- and ␤3-adrenergic receptors (␤-ARs) in white adipose tissue (WAT) of ob/ob mice. Consistent with results of in vivo studies, inhibition of PKC␤ in WAT explants from ob/ob mice increased expression of above ␤-ARs. In contrast, induction of PGC-1␣ and UCP-1 expression in brown adipose tissue of DBKO mice was not accompanied by changes in the expression of these ␤-ARs. In contrast, induction of PGC-1␣ and UCP-1 expression in brown adipose tissue of DBKO mice was not accompanied by changes in the expression of these ␤-ARs These findings suggest that PKC␤ deficiency may prevent genetic obesity, in part, by remodeling the catabolic function of adipose tissues through ␤-ARs dependent and independent mechanisms.—Huang, W., R.

Methods

Results

Conclusion