Mitochondrial uncoupler SHC517 reverses obesity in mice without affecting food intake.

摘要: Abstract Aims Mitochondrial uncouplers decrease caloric efficiency and have potential therapeutic benefits for the treatment of obesity related metabolic disorders. Herein we investigate physiologic effects a recently identified small molecule mitochondrial uncoupler named SHC517 in mouse model diet-induced obesity. Methods was administered as an admixture food. The effect on vivo energy expenditure respiratory quotient determined by indirect calorimetry. A dose-finding prevention study performed starting concomitant with high fat diet period 12 days. An reversal feeding mice western 4 weeks prior to 7 weeks. Biochemical assays were used determine changes glucose, insulin, triglycerides, cholesterol. concentrations mass spectrometry. Results increased lipid oxidation without affecting body temperature. prevented when at 0.05% 0.1% w/w reversed established tested dose. In model, restored adiposity levels similar chow-fed control food intake or lean mass. improved glucose tolerance fasting both modes. Conclusions is potent anti-obesity insulin sensitizing mice. altering compromising mass, that are highly sought-after therapeutics.