The liver X receptor agonist T0901317 protects mice from high fat diet-induced obesity and insulin resistance.

Abstract

The effect of activation of liver X receptor by N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1(trifluoromethyl)ethyl]phenyl] benzenesulfonamide (T0901317) on high fat diet (HFD)-induced obesity and insulin resistance was examined in C57BL/6 mice. When on HFD continuously for 10 weeks, C57BL/6 mice became obese with an average body weight of 42 g, insulin resistant, and glucose intolerant. Twice weekly intraperitoneal injections of T0901317 at 50 mg/kg in animals on the same diet completely blocked obesity development, obesity-associated insulin resistance, and glucose intolerance. Quantitative real-time PCR analysis showed that T0901317-treated animals had significantly higher mRNA levels of genes involved in energy metabolism, including Ucp-1, Pgc1a, Pgc1b, Cpt1a, Cpt1b, Acadm, Acadl, Aox, and Ehhadh. Transcription activation of Cyp7a1, Srebp-1c, Fas, Scd-1, and Acc-1 genes was also seen in T0901317-treated animals. T0901317 treatment induced reversible aggregation of lipids in the liver. These results suggest that liver X receptor could be a potential target for prevention of obesity and obesity-associated insulin resistance.

• Authors: Mingming Gao, Dexi Liu
• Journal: The AAPS journal (AAPS J) Vol. 15 Issue 1 Pg. 258-66 (Jan 2013) ISSN: 1550-7416 [Electronic] United States
• PMID: 23180161 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Hydrocarbons, Fluorinated
• Liver X Receptors
• Orphan Nuclear Receptors
• Sulfonamides
• T0901317
• Glucose

Topics

• Adipose Tissue (drug effects)
• Animals
• Body Composition (drug effects)
• Diet, High-Fat
• Eating (drug effects)
• Energy Metabolism (drug effects)
• Fatty Liver (drug therapy)
• Glucose (metabolism)
• Hydrocarbons, Fluorinated (therapeutic use)
• Insulin Resistance
• Liver X Receptors
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (prevention & control)
• Orphan Nuclear Receptors (agonists)
• Pancreas (drug effects)
• Sulfonamides (therapeutic use)