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Updated: Nov 18, 2025
Body Composition and Metabolic Caging Analysis in High Fat Fed Mice
Published on: May 24, 2018
Mitochondrial uncoupler SHC517 reverses obesity in mice without affecting food intake
Sing-Young Chen1, Martina Beretta1, Stephanie J Alexopoulos1
1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia.
Aims:
Mitochondrial uncouplers decrease caloric efficiency and have potential therapeutic benefits for the treatment of obesity and related metabolic disorders. Herein we investigate the metabolic and physiologic effects of a recently identified small molecule mitochondrial uncoupler named SHC517 in a mouse model of diet-induced obesity.
Methods:
SHC517 was administered as an admixture in food. The effect of SHC517 on in vivo energy expenditure and respiratory quotient was determined by indirect calorimetry. A dose-finding obesity prevention study was performed by starting SHC517 treatment concomitant with high fat diet for a period of 12 days. An obesity reversal study was performed by feeding mice western diet for 4 weeks prior to SHC517 treatment for 7 weeks. Biochemical assays were used to determine changes in glucose, insulin, triglycerides, and cholesterol. SHC517 concentrations were determined by mass spectrometry.
Results:
SHC517 increased lipid oxidation without affecting body temperature. SHC517 prevented diet-induced obesity when administered at 0.05% and 0.1% w/w in high fat diet and reversed established obesity when tested at the 0.05% dose. In the obesity reversal model, SHC517 restored adiposity to levels similar to chow-fed control mice without affecting food intake or lean body mass. SHC517 improved glucose tolerance and fasting glucose levels when administered in both the obesity prevention and obesity reversal modes.
Conclusions:
SHC517 is a mitochondrial uncoupler with potent anti-obesity and insulin sensitizing effects in mice. SHC517 reversed obesity without altering food intake or compromising lean mass, effects that are highly sought-after in anti-obesity therapeutics.
Insights
Mitochondrial uncouplers like SHC517 show promise for treating obesity. This study found SHC517 effectively reversed diet-induced obesity in mice without impacting food intake or lean mass.
Area of Science:
- Metabolic research
- Pharmacology
- Obesity research
Background:
- Mitochondrial uncouplers reduce caloric efficiency.
- They hold therapeutic potential for obesity and metabolic disorders.
Purpose of the Study:
- Investigate the metabolic and physiological effects of the novel mitochondrial uncoupler SHC517.
- Evaluate SHC517 in a mouse model of diet-induced obesity.
Main Methods:
- Administered SHC517 as a food admixture.
- Used indirect calorimetry to measure energy expenditure and respiratory quotient.
- Conducted obesity prevention and reversal studies with biochemical assays.
Main Results:
- SHC517 increased lipid oxidation without affecting body temperature.
- Prevented and reversed diet-induced obesity, restoring adiposity.
- Improved glucose tolerance and fasting glucose levels.
Conclusions:
- SHC517 is a potent mitochondrial uncoupler with anti-obesity and insulin-sensitizing effects.
- Demonstrated obesity reversal without altering food intake or lean mass.
- Highlights SHC517 as a promising anti-obesity therapeutic candidate.
