Research ArticleMetabolism

Controlled-release mitochondrial protonophore (CRMP) reverses dyslipidemia and hepatic steatosis in dysmetabolic nonhuman primates

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Science Translational Medicine  02 Oct 2019:
Vol. 11, Issue 512, eaay0284
DOI: 10.1126/scitranslmed.aay0284

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Uncoupling mitochondria from liver disease

The mitochondrial uncoupler 2,4-dinitrophenol showed potential in treating nonalcoholic fatty liver disease (NAFLD) but was beset by toxicity issues. Here, Goedeke et al. show that a modified, liver-specific mitochondrial uncoupler, previously shown to be effective in rodent models of metabolic disease, improved metabolic symptoms in two diet-induced nonhuman primate models of NAFLD. Their controlled-release mitochondrial protonophore (CRMP) improved insulin resistance, dyslipidemia, and hepatic steatosis in nonhuman primates treated over the course of 6 weeks, without increases in oxidative stress, liver enzymes, or adverse events. This preclinical study supports further work to translate CRMP for the treatment of metabolic diseases in humans.

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