PerspectiveMetabolism

The quest to burn fat, effortlessly and safely

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Science  19 Aug 2016:
Vol. 353, Issue 6301, pp. 749-750
DOI: 10.1126/science.aah6189

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Summary

Treatment of obesity and obesity-associated diseases has been challenging, with the first potential cure claimed in 1934 with the protonophore 2,4-dinitrophenol (DNP). This chemical dissipates mitochondrial membrane potential into heat production and is extremely effective in boosting metabolic rate and promoting weight loss (1). However, severe side effects, including cataract formation, cardiotoxicity, overheating, and death, prevented its further use (2). In a recent study, Long et al. (3) report that a secreted enzyme called peptidase M20 domain containing 1 (PM20D1) converts fatty acids and amino acids into N-acyl amino acids, which directly uncouple mitochondrial membrane potential in a way similar to that of DNP, to increase energy expenditure without physical movement. Might these endogenous metabolites be a safe alternative to chemical uncouplers, facilitating effortless fat burning without a fatal consequence?