Lee Min Hee, Neeland Ian J, de Albuquerque Rocha Natalia, Hughes Connor, Malloy Craig R, Jin Eunsook S
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Department of Medicine, University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Metabol Open. 2021 Dec 25;13:100161. doi: 10.1016/j.metop.2021.100161. eCollection 2022 Mar.
Empagliflozin, a sodium glucose cotransporter 2 inhibitor, is a medication to treat type 2 diabetes. The effect of empagliflozin in persons without diabetes has received less attention. Here we conducted a randomized, double-blind placebo-controlled clinical trial to examine the effect of empagliflozin on plasma triglycerides in obese non-diabetic adults.
Participants (n = 35; BMI ≥ 30 kg/m) underwent body composition assessments using MRI, and were randomly assigned to either placebo or empagliflozin (10 mg/d) for three months. At the baseline and post-treatment visit, after an overnight fast, blood was drawn for biochemical analysis. Participants received [U-C]glycerol orally followed by multiple blood draws over 3 h to examine glycerol incorporation into triglycerides using NMR spectroscopy.
The changes in blood triglyceride concentration with empagliflozin therapy related to the mass of baseline visceral adipose tissue (VAT; r = 0.53, p = 0.04). Empagliflozin slightly lowered triglycerides in obese subjects with low VAT, but increased triglycerides in the subjects with high VAT. Consistently, empagliflozin effectively suppressed triglyceride synthesis following [U-C]glycerol administration in the subjects with low VAT (p < 0.05), but not in the subjects with high VAT. The subjects with high VAT lost body weight after three months of empagliflozin treatment. In all subjects, about 20% of the triglyceride backbone originated from mitochondrial metabolism of glycerol.
The effect of empagliflozin on triglycerides in obese adults differed depending on VAT. Empagliflozin suppressed triglyceride synthesis in the subjects with low VAT, but tended to increase triglycerides in those with high VAT.
恩格列净是一种钠-葡萄糖协同转运蛋白2抑制剂，用于治疗2型糖尿病。恩格列净在非糖尿病患者中的作用较少受到关注。在此，我们进行了一项随机、双盲、安慰剂对照临床试验，以研究恩格列净对肥胖非糖尿病成年人血浆甘油三酯的影响。
参与者（n = 35；BMI≥30 kg/m²）接受了磁共振成像（MRI）身体成分评估，并被随机分配接受安慰剂或恩格列净（10 mg/d）治疗三个月。在基线和治疗后访视时，过夜禁食后采集血液进行生化分析。参与者口服[U-¹³C]甘油，随后在3小时内多次采血，使用核磁共振波谱法检测甘油掺入甘油三酯的情况。
恩格列净治疗后血甘油三酯浓度的变化与基线内脏脂肪组织（VAT）的质量相关（r = 0.53，p = 0.04）。恩格列净使低VAT肥胖受试者的甘油三酯略有降低，但使高VAT受试者的甘油三酯升高。同样，恩格列净在低VAT受试者中有效抑制了[U-¹³C]甘油给药后的甘油三酯合成（p < 0.05），但在高VAT受试者中未观察到这种抑制作用。高VAT受试者在接受三个月恩格列净治疗后体重减轻。在所有受试者中，约20%的甘油三酯骨架源自甘油的线粒体代谢。
恩格列净对肥胖成年人甘油三酯的影响因VAT而异。恩格列净抑制了低VAT受试者的甘油三酯合成，但倾向于使高VAT受试者的甘油三酯升高。
