Cao Chao, Koh Han-Chow E, Van Vliet Stephan, Patterson Bruce W, Reeds Dominic N, Laforest Richard, Gropler Robert J, Mittendorfer Bettina
Center for Human Nutrition, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States of America.
Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110, United States of America.
Metabolism. 2022 Jul;132:155216. doi: 10.1016/j.metabol.2022.155216. Epub 2022 May 13.
Although it is well-accepted that increased plasma free fatty acid (FFA) concentration causes lipid overload and muscle insulin resistance in people with obesity, plasma FFA concentration poorly predicts insulin-resistant glucose metabolism. It has been proposed that hyperinsulinemia in people with obesity sufficiently inhibits adipose tissue triglyceride lipolysis to prevent FFA-induced insulin resistance. However, we hypothesized enhanced FFA clearance in people with obesity, compared with lean people, prevents a marked increase in plasma FFA even when FFA appearance is high.
We assessed FFA kinetics during basal conditions and during a hyperinsulinemic-euglycemic clamp procedure in 14 lean people and 46 people with obesity by using [C]palmitate tracer infusion. Insulin-stimulated muscle glucose uptake rate was evaluated by dynamic PET-imaging of skeletal muscles after [F]fluorodeoxyglucose injection.
Plasma FFA clearance was accelerated in participants with obesity and correlated negatively with muscle insulin sensitivity without a difference between lean and obese participants. Furthermore, insulin infusion increased FFA clearance and the increase was greater in obese than lean participants.
Our findings suggest plasma FFA extraction efficiency, not just plasma FFA concentration, is an important determinant of the cellular fatty acid load and the stimulatory effect of insulin on FFA clearance counteracts some of its antilipolytic effect.
尽管人们普遍认为，肥胖人群血浆游离脂肪酸（FFA）浓度升高会导致脂质超载和肌肉胰岛素抵抗，但血浆FFA浓度并不能很好地预测胰岛素抵抗性葡萄糖代谢。有人提出，肥胖人群的高胰岛素血症会充分抑制脂肪组织甘油三酯的脂解作用，以防止FFA诱导的胰岛素抵抗。然而，我们推测，与瘦人相比，肥胖人群FFA清除能力增强，即使FFA生成量很高，也能防止血浆FFA显著升高。
我们通过输注[C]棕榈酸示踪剂，评估了14名瘦人和46名肥胖者在基础状态下以及高胰岛素-正常血糖钳夹过程中的FFA动力学。注射[F]氟脱氧葡萄糖后，通过骨骼肌动态PET成像评估胰岛素刺激的肌肉葡萄糖摄取率。
肥胖参与者的血浆FFA清除加快，且与肌肉胰岛素敏感性呈负相关，瘦人和肥胖参与者之间无差异。此外，输注胰岛素可增加FFA清除，且肥胖参与者的增加幅度大于瘦人。
我们的研究结果表明，血浆FFA提取效率而非血浆FFA浓度，是细胞脂肪酸负荷的重要决定因素，胰岛素对FFA清除的刺激作用抵消了其部分抗脂解作用。
