Mehta Kamal D
Kamal D Mehta, Department of Molecular and Cellular Biochemistry, The Ohio State University College of Medicine, Dorothy M Davis Heart and Lung Center, Columbus, OH 43210, United States.
World J Diabetes. 2014 Jun 15;5(3):385-92. doi: 10.4239/wjd.v5.i3.385.
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.
蛋白激酶C-β（PKCβ）是脂质激活的丝氨酸/苏氨酸蛋白激酶C家族的成员，参与了广泛的重要细胞过程。最近，人们探索了PKCβ在通过调节线粒体功能来调控甘油三酯稳态中的新作用。在这篇综述中，我旨在概述PKCβ在脂质调节方面的情况，以及最近关于其在能量稳态中作用的相关知识。脂肪组织中PKCβ表达的改变已被证明对饮食诱导的肥胖及相关代谢异常至关重要。高脂饮食被证明以一种异构体和组织特异性的方式诱导白色脂肪组织中PKCβ的表达。基因操作去除PKCβ的小鼠体型瘦，耗氧量增加，对高脂饮食诱导的肥胖和肝脂肪变性具有抗性，胰岛素敏感性也有所改善。现有数据支持这样一种模型，即PKCβ作为一种“饮食敏感”的代谢传感器，高脂饮食在脂肪组织中诱导其表达是通过与p66（Shc）信号通路交叉来破坏线粒体稳态的起始事件之一，从而放大脂肪功能障碍并产生全身性后果。PKCβ表达和/或功能的改变可能对健康和疾病具有重要意义，值得对其下游靶基因和潜在机制进行详细研究。开发靶向PKCβ途径的药物以及鉴定特异性控制PKCβ表达的微小RNA（miR）可能会为治疗包括脂肪肝、肥胖症和2型糖尿病在内的与年龄相关代谢疾病带来新的治疗选择。
