Gender-dependent effect of Gpbar1 genetic deletion on the metabolic profiles of diet-induced obese mice
| Autor: | Galya Vassileva, Lizbeth M. Hoos, Glen Tetzloff, Eric L. Gustafson, Harry R. Davis, Li Liu, Ling Kang, Shijun Yang, Joseph A. Hedrick, Hong Lan, Timothy J. Kowalski, Weiwen Hu |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Blood sugar Biology Receptors G-Protein-Coupled Mice chemistry.chemical_compound Endocrinology Insulin resistance Risk Factors Internal medicine medicine Animals Glucose homeostasis Obesity Triglycerides Mice Knockout Sex Characteristics Triglyceride Incidence Insulin medicine.disease Dietary Fats G protein-coupled bile acid receptor Fatty Liver Mice Inbred C57BL Disease Models Animal Cholesterol chemistry Female Insulin Resistance Steatosis Energy Metabolism Diet-induced obese Gene Deletion |
| Zdroj: | Journal of Endocrinology. 205:225-232 |
| ISSN: | 1479-6805 0022-0795 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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