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

in European Journal of Endocrinology
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  • 1 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China
  • | 2 Department of Medicine, The University of Hong Kong, Hong Kong, China
  • | 3 Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China
  • | 4 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong, China
  • | 5 Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China
  • | 6 Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong, China

Correspondence should be addressed to K S L Lam or A Xu; Email: ksllam@hku.hk or amxu@hku.hk

*(R Yang, Y Hu and C H Lee contributed equally to this work)

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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.

Supplementary Materials

 

     European Society of Endocrinology

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