a Department of Human Biology , NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+ , Maastricht , The Netherlands.
Adipocyte. 2018 Jan 2;7(1):12-19. doi: 10.1080/21623945.2017.1394537. Epub 2018 Feb 5.
Adipose tissue autophagy (AT) is associated with human obesity and increased metabolic risk. Recent findings establish a role for autophagy in lipid metabolism. Here, we compared the expression of autophagy-related and lipolysis genes in human abdominal subcutaneous AT (SCAT) in overweight/obese subjects (n = 17) with or without impaired glucose tolerance in comparison with lean normal glucose tolerant individuals (n = 9), and investigated the association between AT autophagy and lipolysis. Human multipotent adipose-derived stem cells (hMADS) were used to investigate the effect of pharmacological HSL inhibition on changes in the autophagic flux. The expression of autophagy-related genes (ATG) 5, 7 and 12 in SCAT was significantly higher (p = 0.043, p = 0.015, p = 0.004, respectively) in overweight/obese compared to lean men, while expression of the classical lipases HSL (p = 0.092) and ATGL (p = 0.084) tended to be lower. ATG12 mRNA was positively correlated with BMI (r = 0.407, p = 0.039). ATG7 mRNA correlated positively with waist/hip ratio (WHR) (r = 0.420, p = 0.041), 2 h glucose concentration (r = 0.488, p = 0.011) and insulin (r = 0.419, p = 0.033). Multiple linear regressions revealed that ATG7 gene expression was positively related to 2 h glucose, independent of BMI, WHR and insulin. Gene expression interaction analysis showed that ATG7 mRNA negatively correlated with HSL (p<0.01) and ATGL mRNA expression (p<0.01). In line, treatment of differentiated hMADS with an HSL inhibitor increased LC3 accumulation, a marker of increased autophagic flux. Collectively, the present study demonstrated that a low expression of classical lipases in abdominal SCAT is accompanied by an increased expression of ATGs in overweight/obese subjects, which seems to be mainly related to glucose tolerance.
脂肪组织自噬 (AT) 与人类肥胖和代谢风险增加有关。最近的研究结果确立了自噬在脂质代谢中的作用。在这里，我们比较了超重/肥胖患者（n=17）和非肥胖正常糖耐量个体（n=9）腹部皮下脂肪组织 (SCAT) 中自噬相关和脂解基因的表达，并研究了 AT 自噬与脂解之间的关系。人类多能脂肪衍生干细胞 (hMADS) 用于研究药理学 HSL 抑制对自噬通量变化的影响。与瘦人相比，超重/肥胖男性的 SCAT 中自噬相关基因 (ATG) 5、7 和 12 的表达明显更高（p=0.043、p=0.015、p=0.004），而经典脂肪酶 HSL（p=0.092）和 ATGL（p=0.084）的表达趋势较低。ATG12 mRNA 与 BMI 呈正相关（r=0.407，p=0.039）。ATG7 mRNA 与腰围/臀围比（WHR）呈正相关（r=0.420，p=0.041）、2 小时血糖浓度（r=0.488，p=0.011）和胰岛素（r=0.419，p=0.033）。多元线性回归显示，ATG7 基因表达与 2 小时血糖呈正相关，与 BMI、WHR 和胰岛素无关。基因表达相互作用分析显示，ATG7 mRNA 与 HSL（p<0.01）和 ATGL mRNA 表达呈负相关（p<0.01）。与此一致，用 HSL 抑制剂处理分化的 hMADS 会增加 LC3 积累，这是自噬通量增加的标志物。总的来说，本研究表明，超重/肥胖患者腹部 SCAT 中经典脂肪酶表达降低，同时 ATG 表达增加，这似乎主要与葡萄糖耐量有关。
