Brown and beige adipocytes are specialized cells that express uncoupling protein 1 (UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders.
Brown and beige adipocytes are specialized cells that express uncoupling protein 1 ( UCP1 ) and dissipate chemical energy as heat . These cells likely possess alternative UCP1-independent thermogenic mechanisms . Here , we identify a secreted enzyme , peptidase M20 domain containing 1 ( PM20D1 ) , that is enriched in UCP1(+ ) versus UCP1(- ) adipocytes . We demonstrate that PM20D1 is a bidirectional enzyme in vitro , catalyzing both the condensation of fatty acids and amino acids to generate N - acyl amino acids and also the reverse hydrolytic reaction . N - acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration . Mice with increased circulating PM20D1 have augmented respiration and increased N - acyl amino acids in blood . Lastly , administration of N - acyl amino acids to mice improves glucose homeostasis and increases energy expenditure . These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis . This pathway might be useful for treating obesity and associated disorders .
Where is the enzyme PM20D1 localized?
Where is the enzyme PM20D1 localized ?
UCP1+ adipocytes
UCP1+ adipocytes