title: Gender-dependent effect of Gpbar1 genetic deletion on the metabolic profiles of diet-induced obese mice.
abstract: G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5/M-Bar/GPR131) is a cell surface receptor involved in the regulation of bile acid metabolism. We have previously shown that Gpbar1-null mice are resistant to cholesterol gallstone disease when fed a lithogenic diet. Other published studies have suggested that Gpbar1 is involved in both energy homeostasis and glucose homeostasis. Here, we examine the functional role of Gpbar1 in diet-induced obese mice. We found that body weight, food intake, and fasted blood glucose levels were similar between Gpbar1-null mice and their wild-type (WT) littermates when fed a chow or high-fat diet (HFD) for 2 months. However, insulin tolerance tests revealed improved insulin sensitivity in male Gpbar1(-/-) mice fed chow, but impaired insulin sensitivity when fed a HFD. In contrast, female Gpbar1(-/-) mice exhibited improved insulin sensitivity when fed a HFD compared with their WT littermates. Female Gpbar1(-/-) mice had significantly lower plasma cholesterol and triglyceride levels than their WT littermates on both diets. Male Gpbar1(-/-) mice on HFD displayed increased hepatic steatosis when compared with Gpbar1(+)(/)(+) males and Gpbar1(-/-) females on HFD. These results suggest a gender-dependent regulation of Gpbar1 function in metabolic disease.
authors.affiliation: Merck Research Laboratories, Department of Discovery Technologies, Kenilworth, New Jersey 07033, USA.
authors.forename: Galya
authors.initials: G
authors.lastname: Vassileva
authors.forename: Weiwen
authors.initials: W
authors.lastname: Hu
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Hoos
authors.forename: Glen
authors.initials: G
authors.lastname: Tetzloff
authors.forename: Shijun
authors.initials: S
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Kang
authors.forename: Harry R
authors.initials: HR
authors.lastname: Davis
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Hedrick
authors.forename: Hong
authors.initials: H
authors.lastname: Lan
authors.forename: Timothy
authors.initials: T
authors.lastname: Kowalski
authors.forename: Eric L
authors.initials: EL
authors.lastname: Gustafson
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats / Q000009:adverse effects*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005234:Fatty Liver / Q000453:epidemiology; D005260:Female; D017353:Gene Deletion; D015994:Incidence; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D012727:Sex Characteristics; D014280:Triglycerides / Q000097:blood
chemical_list: D004041:Dietary Fats; C513561:Gpbar1 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014280:Triglycerides; D002784:Cholesterol