Circulating total and intact GDF-15 levels are not altered in response to weight loss induced by liraglutide or lorcaserin treatment in humans with obesity

利拉鲁肽 内科学 内分泌学 兴奋剂 安慰剂 减肥 医学 2型糖尿病 肥胖 受体 糖尿病 替代医学 病理
作者
Laura Valenzuela‐Vallejo,Pavlina Chrysafi,Jenny C. Bello-Ramos,Shahd Bsata,Christos S. Mantzoros
出处
期刊:Metabolism-clinical and Experimental [Elsevier]
卷期号:133: 155237-155237 被引量:14
标识
DOI:10.1016/j.metabol.2022.155237
摘要

Background Growth differentiation factor 15 (GDF-15) is a stress-response cytokine proposed to be associated with body weight regulation. Aims The primary aim was to investigate changes of circulating intact GDF-15 (wildtype, non-carrier of the rs1058587 polymorphism coding for the H2O2D mutation) and total GDF-15 (measured irrespective of the mutation) in response to liraglutide (GLP-1 receptor agonist) and lorcaserin (5-HT2C receptor agonist), two pharmacologic agents that induce food intake and weight reduction. In addition, we perform exploratory correlations of total and intact GDF-15 with clinical, hormonal and metabolo-lipidomic parameters in humans with obesity. Materials and methods We utilized two studies: 1) Study 1, a randomized, double-blinded, cross-over trial of liraglutide and placebo administration for 5 weeks in subjects with obesity (n = 20; BMI = 35.6 ± 5.9 kg/m2), in escalating doses starting at 0.6 mg/day on week 1 and increased every week, up to the highest dose of 3.0 mg/day during week 5. b) Study 2, a randomized, double-blinded trial of lorcaserin 10 mg twice daily, or placebo for 12-weeks in humans with obesity (n = 34 BMI = 37.4 ± 6.1 kg/m2). Total and intact GDF-15 levels were measured with novel enzyme-linked immunosorbent assays and the metabolomics and lipidomics analysis was performed with nuclear magnetic resonance spectroscopy. Results Total and intact GDF-15 were positively correlated with diabetes risk index and trimethylamine N-oxide and negatively with eGFR. Despite significant changes in body weight, total and intact GDF-15 were not altered in response to liraglutide or lorcaserin treatment in subjects with obesity. Conclusions Total and intact GDF-15 levels are not altered in response to liraglutide or lorcaserin therapy and are thus not directly involved in the metabolic feedback loop pathways downstream of GLP1 or 5-HT2C receptor agonists. Since neither total nor intact GDF-15 levels were altered in response to weight loss, future studies are needed to elucidate the pathways activated by GDF-15 in humans and its role, if any, in body weight regulation and energy homeostasis.
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