TY - JOUR
T1 - PM20D1 is a circulating biomarker closely associated with obesity, insulin resistance and metabolic syndrome
AU - Yang, Ranyao
AU - Hu, Yue
AU - Lee, Chi Ho
AU - Liu, Yan
AU - Diaz-Canestro, Candela
AU - Fong, Carol Ho Yi
AU - Lin, Huige
AU - Cheng, Kenneth K.Y.
AU - Pravelil, Aparna Padmanabhan
AU - Song, Erfei
AU - Lam, Karen S.L.
AU - Xu, Aimin
N1 - Funding Information:
This work was supported by Hong Kong Research Grants Council/Area of Excellence (AoE/M/707-18), Collaborative Research Fund (C7037-17W), National key R&D programmes (2017YFE0190200) and National Natural Science Foundation of China (81800754).
Publisher Copyright:
© 2022 European Society of Endocrinology
PY - 2021/12
Y1 - 2021/12
N2 - Objective: 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. Design and methods: 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. Results: 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. Conclusions: 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.
AB - Objective: 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. Design and methods: 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. Results: 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. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=85122548771&partnerID=8YFLogxK
U2 - 10.1530/EJE-21-0847
DO - 10.1530/EJE-21-0847
M3 - Journal article
C2 - 34757919
AN - SCOPUS:85122548771
SN - 0804-4643
VL - 186
SP - 151
EP - 161
JO - European Journal of Endocrinology
JF - European Journal of Endocrinology
IS - 2
ER -