Loss of protein kinase Cβ function protects mice against diet-induced obesity and development of hepatic steatosis and insulin resistance

Authors

  • Wei Huang,

    1. Departments of Molecular and Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH
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  • Rishipal Bansode,

    1. Departments of Molecular and Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH
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  • Madhu Mehta,

    1. Department of Internal Medicine, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH
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  • Kamal D. Mehta

    Corresponding author
    1. Departments of Molecular and Cellular Biochemistry, Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, OH
    • Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, 464 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210
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    • fax: 614-292-4118


  • Potential conflict of interest: Nothing to report.

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 β-isoform of protein kinase C (PKCβ), 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 PKCβ expression and the effect of PKCβ deficiency on profound weight gain. We report herein that HFD selectively increased PKCβ 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 PKCβ expression was also found to be elevated in WAT of obese ob/ob mice. Remarkably, mice lacking PKCβ 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, PKCβ−/− mice exhibited changes in lipid metabolism gene expression, and such alterations were accompanied by significant changes in serum adipokines. These observations suggest that PKCβdeficiency induced a unique metabolic state congruous with obesity resistance, thus raising the possibility that dysregulation of PKCβ expression could contribute to dietary fat–induced obesity and related disorders. (HEPATOLOGY 2009.)

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