PM20D1 is a circulating biomarker closely associated with obesity, insulin resistance and metabolic syndrome

内科学 内分泌学 胰岛素抵抗 代谢综合征 餐后 2型糖尿病 超重 胰岛素 肥胖 磺酰脲 医学 化学 产热 糖尿病
作者
Ranyao Yang,Yue Hu,Chi‐Ho Lee,Yan Liu,Candela Díaz-Cañestro,Carol Ho Yi Fong,Huige Lin,Kenneth K.Y. Cheng,Aparna Padmanabhan Pravelil,Erfei Song,Karen S.L. Lam,Aimin Xu
出处
期刊:European journal of endocrinology [Bioscientifica]
卷期号:186 (2): 151-161 被引量:14
标识
DOI:10.1530/eje-21-0847
摘要

Peptidase M20 domain containing 1 (PM20D1), a secreted enzyme catalysing condensation of fatty acids and amino acids into the bioactive lipids N-acyl amino acids (NAAA), induces uncoupling protein 1 (UCP1)-independent adaptive thermogenesis in brown/beige adipocytes in mice. This study aimed to explore the associations of the circulating levels of PM20D1 and major NAAA with obesity-related metabolic complications in humans.Serum concentrations of PM20D1 and NAAA (C18:1-Leu and C18:1-Phe) in 256 Chinese subjects, including 78 lean and 178 overweight/obese individuals with or without diabetes, were measured with immunoassays and liquid chromatography-mass spectrometry, respectively. The impact of sulfonylurea and rosiglitazone on their circulating levels was examined in 62 patients with type 2 diabetes.Serum PM20D1 level was significantly elevated in overweight/obese individuals and was closely associated with circulating levels of C18:1-Leu and C18:1-Phe. Furthermore, serum PM20D1, C18:1-Leu and C18:1-Phe concentrations correlated positively with several parameters of adiposity as well as fasting and 2 h postprandial glucose, HbA1c, fasting insulin and HOMA-IR independent of BMI and age. Moreover, a significant elevation in PM20D1, C18:1-Leu and C18:1-Phe concentrations corresponding with increases in the number of components of the metabolic syndrome (MetS) was observed. Treatment with sulfonylurea significantly decreased circulating PM20D1, C18:1-Leu and C18:1-Phe in patients with type 2 diabetes.Increased serum levels of PM20D1 and its catalytic products NAAA are closely associated with obesity-related glucose dysregulation, insulin resistance and MetS and can be potentially used as clinical biomarkers for diagnosing and monitoring these disorders.
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