Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity.

Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity.
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DOI:
10.3390/ijms222312945
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发表时间:
2021-11-30
影响因子:
5.6
通讯作者:
Rodríguez A
Rodríguez A
中科院分区:
生物学2区
文献类型:
--
作者:
Perdomo CM;Gómez-Ambrosi J;Becerril S;Valentí V;Moncada R;Fernández-Sáez EM;Méndez-Giménez L;Ezquerro S;Catalán V;Silva C;Escalada J;Frühbeck G;Rodríguez A

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血管生成素样蛋白 8 (ANGPTL8) 是一种肝因子,会在多种代谢条件下发生改变,例如肥胖、2 型糖尿病、血脂异常和非酒精性脂肪肝 (NAFLD)。我们试图探讨 ANGPTL8 是否参与实验模型和重度肥胖患者减肥手术后 NAFLD 的改善。在减肥手术前和术后 6 个月对 170 名个体的血浆 ANGPTL8 进行了测量。通过可用的肝脏病理学分析,在接受减肥手术的严重肥胖患者的肝活检中评估了肝脏 ANGPTL8 的表达(n = 75),以及在接受假手术、袖状胃切除术或 Roux-en-Y 胃绕道术 (RYGB) 的饮食诱导肥胖的雄性 Wistar 大鼠中评估了肝脏 ANGPTL8 的表达(n = 65)。在棕榈酸酯诱导的脂毒性条件下,评估了 ANGPTL8 对人 HepG2 肝细胞脂肪生成的影响。在肥胖相关 NAFLD 患者中,ANGPTL8 的血浆浓度和肝脏表达增加,且与肝脏脂肪变性程度相关。袖状胃切除术和 RYGB 可改善 NAFLD 临床前模型中的肝脂肪变性并降低肝脏 ANGPTL8 的表达。有趣的是,ANGPTL8 抑制棕榈酸酯处理的人肝细胞中的脂肪变性和脂肪生成因子(PPARG2、SREBF1、MOGAT2 和 DGAT1)的表达。总之,ANGPTL8 部分通过抑制脂肪肝细胞中的脂肪生成来参与减肥手术后 NAFLD 的缓解。
Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (n = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (n = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (PPARG2, SREBF1, MOGAT2 and DGAT1) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.
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