New drug candidate reverses obesity in mice by transforming liver metabolism

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Liver News

Metabolism,Obesity,Adipose

A mitochondrial transcription inhibitor (IMT) shifted metabolism in high-fat diet mice toward fatty acid oxidation, leading to weight loss, reduced liver fat, and improved glucose tolerance.

By Dr. Sushama R. Chaphalkar, PhD.May 1 2024Reviewed by Susha Cheriyedath, M.Sc. In a study published in the journal Nature Metabolism, researchers treated male mice on a high-fat diet with an inhibitor of mitochondrial transcription . They found that this shifted the mice's metabolism towards fatty acid oxidation, leading to weight loss, reversal of hepatosteatosis, and improved glucose tolerance.

About the study Male C57BL/6N mice were divided into chow or HFD groups for eight weeks, then subdivided for 4-week treatment with IMT or vehicle. Mice were monitored using the Comprehensive Lab Animal Monitoring System for five days. Fecal lipid content, energy content, and respiratory exchange ratio were analyzed. Blood glucose and serum insulin levels were measured, and intraperitoneal glucose tolerance tests were conducted.

IMT treatment in HFD-fed mice rapidly reduced body weight by approximately 7 g after four weeks, primarily due to decreased fat mass without affecting lean mass. Histological analysis showed reduced adipocyte size in white adipose tissue. IMT treatment did not affect food intake, physical activity, or fecal lipid content. There was no significant change in total energy content in feces, suggesting IMT-induced weight loss is not due to malabsorption.

IMT treatment significantly reduced hepatosteatosis in HFD-fed mice, accompanied by decreased liver lipid content and weight. A reversal of diglyceride and triglyceride accumulation was observed in the liver. Liver function improved with reduced serum aminotransferase activities. Serum albumin levels remained normal. These results indicate that IMT effectively reversed diet-induced hepatosteatosis and normalized liver function.

 

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