Steno Diabetes Center Aarhus, Aarhus University Hospital (AUH), Aarhus, Denmark.
Steno Diabetes Center Aarhus, Aarhus University Hospital (AUH), Aarhus, Denmark; Department of Endocrinology and Internal Medicine, AUH, Aarhus, Denmark.
J Lipid Res. 2024 Jul;65(7):100580. doi: 10.1016/j.jlr.2024.100580. Epub 2024 Jun 18.
This study aimed to determine whether obese men with nonalcoholic fatty liver disease (NAFLD) display differences between those with simple steatosis versus steatohepatitis (NASH) in splanchnic and hepatic FFA and VLDL-triglycerides (VLDL-TG) balances. The study involved 17 obese men with biopsy-proven NAFLD (9 with NASH and 8 with simple steatosis). We used hepatic vein catheterization in combination with [H]palmitate and [C]VLDL-TG tracers to measure splanchnic palmitate and VLDL-TG uptake and release rates during basal and hyperinsulinemic conditions. Indocyanine green was used to measure splanchnic plasma flow. Splanchnic palmitate uptake was similar in the two groups and significantly reduced during hyperinsulinemia (NASH: 62 (48-77) versus 38 (18-58) μmol/min; simple steatosis: 62 (46-78) versus 45 (25-65) μmol/min, mean (95% CI), basal versus clamp periods, respectively, P = 0.02 time-effect). Splanchnic palmitate release was also comparable between groups and nonsignificantly diminished during hyperinsulinemia. The percent palmitate delivered to the liver originating from visceral adipose tissue lipolysis was similar and unchanged by hyperinsulinemia. Splanchnic uptake and release of VLDL-TG were similar between groups. Hyperinsulinemia suppressed VLDL-TG release (P <0.05 time-effect) in both groups. Insulin-mediated glucose disposal was similar in the two groups (P = 0.54). Obese men with NASH and simple steatosis have similar splanchnic uptake and release of FFA and VLDL-TG and a similar proportion of FFA from visceral adipose tissue lipolysis delivered to the liver. These results demonstrate that the splanchnic balances of FFA and VLDL-TG do not differ between obese men with NASH and those with simple steatosis.
本研究旨在确定非酒精性脂肪性肝病(NAFLD)合并肥胖的男性中,单纯性脂肪变性与脂肪性肝炎(NASH)患者在内脏脂肪组织和肝脏游离脂肪酸(FFA)与极低密度脂蛋白甘油三酯(VLDL-TG)平衡方面是否存在差异。该研究纳入了 17 名经肝活检证实为 NAFLD 的肥胖男性(9 名 NASH 患者和 8 名单纯性脂肪变性患者)。我们采用肝静脉插管技术,并联合使用[H]棕榈酸和[C]VLDL-TG 示踪剂,在基础状态和高胰岛素血症条件下测量内脏组织摄取和释放 FFA 和 VLDL-TG 的速率。采用吲哚菁绿测量内脏组织血流。两组患者的内脏组织摄取棕榈酸的速率相似,且在高胰岛素血症条件下均显著降低(NASH:62(48-77)比 38(18-58)μmol/min;单纯性脂肪变性:62(46-78)比 45(25-65)μmol/min,均值(95%CI),基础期与钳夹期相比,P=0.02 时间效应)。内脏组织释放棕榈酸的速率在两组间也相似,且在高胰岛素血症条件下无显著降低。来源于内脏脂肪组织脂解的棕榈酸向肝脏输送的比例在两组间相似,且不受高胰岛素血症影响。内脏组织摄取和释放 VLDL-TG 在两组间相似。高胰岛素血症抑制了两组 VLDL-TG 的释放(P<0.05 时间效应)。两组间胰岛素介导的葡萄糖处置率相似(P=0.54)。NASH 合并单纯性脂肪变性的肥胖男性的内脏组织 FFA 和 VLDL-TG 摄取和释放以及来源于内脏脂肪组织脂解的 FFA 向肝脏输送的比例相似。这些结果表明,NASH 合并单纯性脂肪变性的肥胖男性的内脏组织 FFA 和 VLDL-TG 平衡并无差异。