Emerging role of protein kinase C in energy homeostasis: A brief overview

Abstract

Protein kinase C-β (PKCβ), a member of the lipid-activated serine/threonine PKC family, has been implicated in a wide range of important cellular processes. Very recently, the novel role of PKCβ in the regulation of triglyceride homeostasis via regulating mitochondrial function has been explored. In this review, I aim to provide an overview of PKCβ regarding regulation by lipids and recently gained knowledge on its role in energy homeostasis. Alterations in adipose PKCβ expression have been shown to be crucial for diet-induced obesity and related metabolic abnormalities. High-fat diet is shown to induce PKCβ expression in white adipose tissue in an isoform- and tissue-specific manner. Genetically manipulated mice devoid of PKCβ are lean with increased oxygen consumption and are resistant to high-fat diet-induced obesity and hepatic steatosis with improved insulin sensitivity. Available data support the model in which PKCβ functions as a “diet-sensitive” metabolic sensor whose induction in adipose tissue by high-fat diet is among the initiating event disrupting mitochondrial homeostasis via intersecting with p66^Shc signaling to amplify adipose dysfunction and have systemic consequences. Alterations in PKCβ expression and/or function may have important implications in health and disease and warrants a detailed investigation into the downstream target genes and the underlying mechanisms involved. Development of drugs that target the PKCβ pathway and identification of miRs specifically controlling PKCβ expression may lead to novel therapeutic options for treating age-related metabolic disease including fatty liver, obesity and type 2 diabetes.

Keywords: High-fat diet; Signal transduction; Obesity; Mitochondrial function; Insulin resistance

Core tip: Nutrition has important long-term consequences for health. It is one of the lifestyle factors that contribute to the development and progression of obesity (increased fat accumulation), diabetes, and cardiovascular diseases. In fact, obesity rates are increasing dramatically worldwide and obesity amplifies the risk of developing various age-related chronic diseases, such as type 2 diabetes and cardiovascular disease. The prevention or management of chronic diseases is a global priority since they constitute a serious strain on health care systems and account for more than half of the deaths worldwide. Although correct lifestyle remains the mainstream solution to this problem, pharmacological strategies are also being actively seeked. Current antiobesity strategies have not controlled increasing epidemic of obesity and obesity-related disorders. We hope that a better knowledge of the molecular players and biochemical mechanism linking dietary fat to fat accumulation and development of glucose intolerance are critically needed. This review examines a way of metabolizing dietary fat into heat instead of storing them as fat, and the possibility that the “browning” of white fat is regulated by a diet-inducible kinase Protein kinase C-β (PKCβ) may help us explore new translational approaches to combat obesity, improve insulin sensitivity and potentially increase longevity. Finally, attenuation of inflammation in fat by PKCβ inhibition could have profound clinical consequences because of the large size of the fat organ and its central metabolic role.