Department of Nutrition and Health Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
Biochem Biophys Res Commun. 2013 Sep 27;439(3):390-5. doi: 10.1016/j.bbrc.2013.08.063. Epub 2013 Aug 29.
Controlling elevated blood triacylglycerol translates into substantial health benefits. The present study aimed to evaluate the triacylglycerol-lowering properties of (R)-α-lipoic acid (LA) once circulating triacylglycerol levels have become elevated, and identify the molecular targets of LA. Nine-week old male ZDF (fa/fa) rats were fed a chow diet supplemented with 3g LA per kg diet or pair fed for two weeks (8 rats per treatment). We determined changes in blood triacylglycerol, insulin, non-esterified fatty acids, and ketone bodies concentrations. We analyzed the expression of genes and proteins involved in fatty acid and triacylglycerol metabolism in liver, epididymal fat, and skeletal muscle. Feeding LA to ZDF rats (a) corrected severe hypertriglyceridemia, (b) lowered abdominal fat mass, (c) raised circulating fibroblast growth factor-21 and Fgf21 liver gene expression, (d) repressed lipogenic gene expression of ATP-citrate synthase (Acly), acetyl-coA carboxylase 1 (Acaca), fatty acid synthase (Fasn), sn-glycerol-3-phosphate acyltransferase 1 (Gpam), adiponutrin (Pnpla3) in the liver and adipose tissue, (e) decreased hepatic protein levels of ACC1/2, FASN and 5'-AMP-activated protein kinase catalytic subunit α (AMPKα), (f) did not change phospho-AMPKα/AMPKα and phospho-ACC/ACC ratios, (g) stimulated liver gene expression of PPARα target genes carnitine O-palmitoyltransferase 1β (Cpt1b) and acyl-CoA thioesterase 1 (Acot1) but not carnitine O-palmitoyltransferase 1α (Cpt1a). This is evidence that short-term LA feeding to obese rats reverses severe hypertriglyceridemia. FGF21 may mediate the beneficial metabolic effects of LA.
控制升高的三酰甘油水平可带来显著的健康益处。本研究旨在评估（R）-α-硫辛酸（LA）在循环三酰甘油水平升高后的降三酰甘油作用，并确定 LA 的分子靶点。将 9 周龄雄性 ZDF（fa/fa）大鼠喂食含 3g/kg 饮食 LA 的标准饮食或等热量喂养两周（每组 8 只大鼠）。我们测定了血液三酰甘油、胰岛素、非酯化脂肪酸和酮体浓度的变化。我们分析了肝脏、附睾脂肪和骨骼肌中脂肪酸和三酰甘油代谢相关基因和蛋白的表达。向 ZDF 大鼠喂食 LA：（a）纠正了严重的高甘油三酯血症；（b）降低了腹部脂肪量；（c）提高了循环成纤维细胞生长因子 21 和 Fgf21 肝脏基因表达；（d）抑制了肝脏和脂肪组织中 ATP-柠檬酸合酶（Acly）、乙酰辅酶 A 羧化酶 1（Acaca）、脂肪酸合酶（Fasn）、sn-甘油-3-磷酸酰基转移酶 1（Gpam）、脂滴生成素（Pnpla3）的脂肪生成基因表达；（e）降低了肝组织中 ACC1/2、FASN 和 5'-AMP 激活的蛋白激酶催化亚基α（AMPKα）的蛋白水平；（f）未改变磷酸化-AMPKα/AMPKα 和磷酸化-ACC/ACC 比值；（g）刺激了肝脏中 PPARα 靶基因肉碱 O-棕榈酰转移酶 1β（Cpt1b）和酰基辅酶 A 硫酯酶 1（Acot1）的基因表达，但未改变肉碱 O-棕榈酰转移酶 1α（Cpt1a）的基因表达。这表明，肥胖大鼠短期 LA 喂养可逆转严重的高甘油三酯血症。FGF21 可能介导了 LA 的有益代谢作用。
