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PM20D1 as a key enzyme for energy expenditure
Dana Farber
Protein
Metabolic disease
Target Identification or Validation
The Spiegelman lab has discovered a secreted enzyme, peptidase M20 domain containing 1 (PM20D1), that plays a key role in augmenting energy dissipation in thermogenic adipocytes. PM20D1 is a bidirectional biosynthetic enzyme for a class of N-lipidated amino acids, the metabolites of which are
endogenous uncouplers that regulate mitochondrial respiration. PM20D1 is highly enriched in thermogenic versus non-thermogenic adipocytes and promotes energy expenditure in vivo. Mice with increased circulating PM20D1 show augmented energy expenditure, blunted weight gain on high fat diet, and improved glucose homeostasis. Furthermore, direct treatment of adipocytes with N-lipidated amino acids, such as oleoylphenylalanine, increases oxygen consumption.