Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes
Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes
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DOI：
10.1038/ijo.2009.40
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发表时间：
2009-05-01
影响因子：
4.9
通讯作者：
Fruehbeck, G.
中科院分区：
文献类型：
--
作者：
Rodriguez, A.;Gomez-Ambrosi, J.;Fruehbeck, G.
目的：生长素主要以酰化和去酰化两种形式循环。我们评估了肥胖和肥胖相关的2型糖尿病（T2D）对胃饥饿素形式的影响，以及酰化和去酰化胃饥饿素在控制人类脂肪生成中的潜在作用。方法：对80例受试者进行不同形式胃饥饿素的血药浓度测定。采用western blot和免疫组化方法分析大网膜脂肪组织中生长激素促分泌素受体（growth hormone secretagogue receptor, GHS-R）的表达，并在体外研究大网膜脂肪细胞中去酰化ghrelin和去酰化ghrelin （0.1-1000 pmol l(-1)）对脂肪形成的影响。结果：在肥胖和肥胖相关的T2D中，循环中酰化胃饥饿素浓度升高，而去酰化胃饥饿素水平降低。体重指数、腰围、胰岛素和HOMA（稳态模型评估）指数与酰化胃饥饿素水平呈正相关。肥胖个体大网膜脂肪组织中GHS-R蛋白表达较低。在大网膜脂肪细胞分化过程中，与酰化和去酰化胃饥饿素孵育均可显著提高PPAR γ（过氧化物酶体增殖物激活受体γ）和SREBP1（固醇调节元件结合蛋白-1）mRNA水平，以及几种脂肪储存相关蛋白，包括乙酰辅酶a羧化酶、脂肪酸合成酶、脂蛋白脂肪酶和perilippin。因此，两种饥饿素形式都刺激了胞浆内脂质积累。结论：酰化和去酰化胃饥饿素均可刺激人内脏脂肪细胞的脂质积累。鉴于酰化胃饥饿素对内脏脂肪细胞的致脂作用，本文报道的肥胖个体循环浓度升高可能在肥胖中过度脂肪积累中起作用。国际肥胖杂志（2009）33,541-552；doi: 10.1038 / ijo.2009.40;2009年2月24日在线发布
Objectives: The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans.Methods: Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1-1000 pmol l(-1)) on adipogenesis was determined in vitro in omental adipocytes.Results: Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPAR gamma (peroxisome proliferator-activated receptor gamma) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation.Conclusions: Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity. International Journal of Obesity (2009) 33, 541-552; doi:10.1038/ijo.2009.40; published online 24 February 2009