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Related Experiment Video

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Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

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Reduction in Obesity-Related Hepatic Fibrosis by SR1664.

Benita L McVicker^1,2, Ronda L Simpson^1,2, Frederick G Hamel^1,3

¹Research Service, Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.

|October 27, 2023

Summary

Selective PPARγ modulator SR1664 reduced liver fibrosis and improved insulin sensitivity in mice on a high-fat, high-carbohydrate diet. This suggests targeted PPARγ modulation may treat obesity-related liver disease.

Keywords:

cirrhosis hepatic fibrosis peroxisome-proliferator-activated receptor gamma

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Area of Science:

Pharmacology
Hepatology
Metabolic Diseases

Background:

Peroxisome-proliferator-activated receptor gamma (PPARγ) influences fat metabolism and insulin sensitivity.
While potent PPARγ activators cause side effects, selective modulators like SR1664 are being developed.
Previous studies showed SR1664 reduced toxin-induced liver fibrosis.

Purpose of the Study:

To investigate the efficacy of SR1664 in a high-fat, high-carbohydrate (HFHC) diet model of liver steatosis and fibrosis.
To assess SR1664's impact on metabolic parameters and liver pathology in this model.

Main Methods:

Mice were fed a standard or HFHC diet for 16 weeks, with SR1664 or control treatment during the final 4 weeks.
Evaluated weight gain, fasting glucose and insulin levels, liver triglyceride content, and lipid droplet size.
Assessed liver fibrosis and hepatic stellate cell (HSC) activation.

Main Results:

SR1664 did not affect weight gain or fasting glucose/insulin levels.
SR1664 reduced lipid droplet size but not total liver triglycerides in HFHC mice.
Significant reduction in liver fibrosis and activated HSCs was observed with SR1664 treatment in HFHC mice.

Conclusions:

SR1664 demonstrated effectiveness in reducing liver fibrosis and improving insulin sensitivity in an obesity-related liver disease model.
Selective PPARγ modulation with SR1664 presents a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) and associated fibrosis.