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

Abstract

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.

• Authors: Ranyao Yang, Yue Hu, Chi Ho Lee, Yan Liu, Candela Diaz-Canestro, Carol Ho Yi Fong, Huige Lin, Kenneth K Y Cheng, Aparna Padmanabhan Pravelil, Erfei Song, Karen S L Lam, Aimin Xu
• Journal: European journal of endocrinology (Eur J Endocrinol) Vol. 186 Issue 2 Pg. 151-161 (Dec 10 2021) ISSN: 1479-683X [Electronic] England
• PMID: 34757919 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Biomarkers
• Amidohydrolases
• PM20D1 protein, human

Topics

• Adult
• Aged
• Amidohydrolases (blood)
• Biomarkers (blood)
• Cross-Sectional Studies
• Female
• HEK293 Cells
• Humans
• Insulin Resistance (physiology)
• Male
• Metabolic Syndrome (blood, diagnosis)
• Middle Aged
• Obesity (blood, diagnosis)