Objective: Growth hormone (GH) deficiency has been associated with increased steatosis but the molecular mechanism has not been fully elucidated. We investigated the effect of GH on lipid accumulation of HepG2 cells cultured on an in vitro steatosis model and examined the potential involvement of insulin-like growth factor 1 (IGF-1) as well as lipogenic and lipolytic molecules.

Methods: Control and steatosis conditions were induced by culturing HepG2 cells with 5.5 or 25 mmol/l glucose for 24 h, respectively. Afterward, cells were exposed to 0, 5, 10 or 20 ng/ml GH for another 24 h. Lipid content was quantified as well as mRNA and protein levels of IGF-1, carbohydrate responsive element-binding protein (ChREBP), sterol regulatory element-binding protein 1c (SREBP1c), fatty acid synthase (FAS), carnitine palmitoyltransferase 1A (CPT1A), and peroxisome proliferator-activated receptor alpha (PPAR-alpha) by qPCR and western blot, respectively. Data were analyzed by one-way ANOVA and the Games-Howell post-hoc test.

Results: In the steatosis model, HepG2 hepatocytes showed a significant 2-fold increase in lipid amount as compared to control cells. IGF-1 mRNA and protein levels were significantly increased in control cells exposed to 10 ng/ml GH, whereas high glucose abolished this effect. High glucose also significantly increased both mRNA and protein of ChREBP and FAS without having effect on SREBP1c, CPT1A and PPAR-alpha. However, GH inhibited ChREBP and FAS production, even in HepG2 hepatocytes cultured under steatosis conditions.

Conclusions: Growth hormone ameliorates high glucose-induced steatosis in HepG2 cells by suppressing de novo lipogenesis via ChREBP and FAS down-regulation.

目的：生长激素 (GH) 缺乏与脂肪变性增加有关，但分子机制尚未完全阐明。我们研究了 GH 对体外脂肪变性模型上培养的 HepG2 细胞脂质积累的影响，并检查了胰岛素样生长因子 1 (IGF-1) 以及脂肪生成和脂肪分解分子的潜在参与。

方法：通过分别用 5.5 或 25 mmol/l 葡萄糖培养 HepG2 细胞 24 小时来诱导对照和脂肪变性条件。之后，将细胞暴露于 0、5、10 或 20 ng/ml GH 下另外 24 小时。脂质含量以及 IGF-1、碳水化合物反应元件结合蛋白 (ChREBP)、甾醇调节元件结合蛋白 1c (SREBP1c)、脂肪酸合酶 (FAS)、肉碱棕榈酰转移酶 1A (CPT1A) 的 mRNA 和蛋白质水平被量化和过氧化物酶体增殖物激活受体 α（PPAR-α）分别通过 qPCR 和蛋白质印迹检测。数据通过单向方差分析和 Games-Howell 事后检验进行分析。

结果：在脂肪变性模型中，与对照细胞相比，HepG2肝细胞的脂质量显着增加了2倍。在暴露于 10 ng/ml GH 的对照细胞中，IGF-1 mRNA 和蛋白质水平显着增加，而高葡萄糖消除了这种影响。高糖还显着增加了 ChREBP 和 FAS 的 mRNA 和蛋白质，而对 SREBP1c、CPT1A 和 PPAR-α 没有影响。然而，即使在脂肪变性条件下培养的 HepG2 肝细胞中，GH 也能抑制 ChREBP 和 FAS 的产生。

结论：生长激素通过ChREBP 和 FAS 下调抑制从头脂肪生成来改善 HepG2 细胞中高糖诱导的脂肪变性。