Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Department of Medicine, Division of Infectious Diseases, UCLA David Geffen School of Medicine, Los Angels, California.
Diabetes Obes Metab. 2019 Jun;21(6):1487-1492. doi: 10.1111/dom.13655. Epub 2019 Mar 18.
Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P < 0.001), the fatty liver index (P < 0.0001) and energy intake (P < 0.03) without affecting energy expenditure or lean mass. Total low-density lipoprotein (LDL) (P < 0.04) and small LDL particles (P < 0.03) decreased, while total high-density lipoprotein (HDL) P < 0.02) increased and heart rate significantly decreased with lorcaserin treatment. No mRNA expression of the 5-HT2c receptor was observed in peripheral organs. These data suggest that lorcaserin treatment for six months improves cardiometabolic health in obese individuals, acting mainly through the brain.
盐酸氯卡色林是一种血清素 2C 受体激动剂,可在预防和改善 2 型糖尿病和改善动脉粥样硬化脂质谱的同时促进体重减轻,而不会增加主要心血管事件的发生率。盐酸氯卡色林可能改善心血代谢健康的全部范围仍有待阐明。因此,我们研究了盐酸氯卡色林治疗可能通过改变体重或通过其他方式改变心血管疾病风险的方式。我们首次测量了脂质颗粒定量、脂质过氧化、调节食欲的激素和 5-羟色胺 2C 受体(5-HT2c 受体)的 mRNA 表达。共有 48 名肥胖参与者参与了这项为期 6 个月的、随机(1:1)、安慰剂对照、双盲临床试验。盐酸氯卡色林治疗可降低脂肪量(P<0.001)、脂肪肝指数(P<0.0001)和能量摄入(P<0.03),而不影响能量消耗或瘦体重。总低密度脂蛋白(LDL)(P<0.04)和小 LDL 颗粒(P<0.03)减少,而总高密度脂蛋白(HDL)(P<0.02)增加,心率明显下降。外周器官中未观察到 5-HT2c 受体的 mRNA 表达。这些数据表明,盐酸氯卡色林治疗 6 个月可改善肥胖个体的心血代谢健康,主要通过大脑发挥作用。