title: 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.affiliation: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Gao
authors.forename: Dexi
authors.initials: D
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005234:Fatty Liver / Q000188:drug therapy; D005947:Glucose / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000627:therapeutic use*; D007333:Insulin Resistance; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000517:prevention & control*; D057093:Orphan Nuclear Receptors / Q000819:agonists*; D010179:Pancreas / Q000187:drug effects; D013449:Sulfonamides / Q000627:therapeutic use*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D005947:Glucose; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides