脂滴包被蛋白(perilipin)调控脂肪分解

Perilipin Associated with Lipid Droplets Regulates Lipolysis

脂滴包被蛋白(perilipin)包被在脂肪细胞和甾体生成细胞脂滴表面。基础状态下perilipin可减少甘油三酯水解,使其贮备增加;脂肪分解时磷酸化的perilipin能促进甘油三酯水解,而且该蛋白对激素敏感脂酶从胞浆向脂滴转位是必需的。据推测,perilipin可能在脂肪分解调控中起到“分子开关”的作用。蛋白激酶A(PKA)、细胞外信号调节激酶(ERK)等信号转导通路参与了脂肪分解。肿瘤坏死因子α(TNFα)、过氧化物酶体增殖物激活受体γ(PPARγ)激动剂、瘦素(leptin)均可以影响perilipin的表达。新近研究表明,perilipin可通过蛋白酶体途径来调节其蛋白量的表达。脂肪分解调控中的关键蛋白perilipin可以和2型糖尿病、肥胖、动脉粥样硬化等多种代谢性疾病及心血管疾病联系起来。

Perilipins are the proteins associating with the lipid droplets in adipocytes and steroidogenic ceils. Unphosphorylated perilipins coat the surface of intracellular lipid droplets to form a barrier that prevents lipase from accessing to triacylglycerol core, thus suppressing lipolysis. Upon activation of protein kinase A （PKA）, two proteins, hormone-sensitive lipase （HSL） and perilipins, are phosphorylated. The phosphorylated perilipin is required for inducing the translocation of HSL from the cytosol to the lipid droplets of adipocytes and is essential for the initiation of lipolytic reaction. It is proposed that phosphorylation of perilipin is a key step for the activation of lipolytic cascade via PKA and ERK signaling pathways. Dsyregulation of perilipin involves in the pathogenesis of obesity, diabetes and atherosclerosis.