Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1
| Autor: | Jacquelyn J. Maher, Lorenzo Arnaboldi, Ray K. Ng, Jim Yan, Gene S. Lee, Robert E. Pitas, Gizem Rizki, Thomas M. Badger, Scott M. Turner, Bianca Gabrielli |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty oxidation QD415-436 Biology liver Biochemistry Mice chemistry.chemical_compound Methionine Endocrinology Internal medicine steatosis medicine Animals Choline Beta oxidation Cells Cultured lipogenesis fatty liver chemistry.chemical_classification Fatty liver nutritional and metabolic diseases Fatty acid Cell Biology medicine.disease eye diseases Choline Deficiency Diet Nutrition Disorders chemistry Lipogenesis Hypermetabolism fatty acid Steatosis Stearoyl-CoA Desaturase |
| Zdroj: | Journal of Lipid Research, Vol 47, Iss 10, Pp 2280-2290 (2006) |
| ISSN: | 0022-2275 |
| Popis: | Lipogenic diets that are completely devoid of methionine and choline (MCD) induce hepatic steatosis. MCD feeding also provokes systemic weight loss, for unclear reasons. In this study, we found that MCD feeding causes profound hepatic suppression of the gene encoding stearoyl-coenzyme A desaturase-1 (SCD-1), an enzyme whose regulation has significant effects on metabolic rate. Within 7 days of MCD exposure, hepatic SCD-1 mRNA decreased to nearly undetectable levels. By day 21, SCD-1 protein was absent from hepatic microsomes and fatty acids showed a decrease in monounsaturated species. These changes in hepatic SCD-1 were accompanied by signs of hypermetabolism. Calorimetry revealed that MCD-fed mice consumed 37% more energy than control mice (P = 0.0003). MCD feeding also stimulated fatty acid oxidation, although fatty oxidation genes were not significantly upregulated. Interestingly, despite their increased metabolic rate, MCD-fed mice did not increase their food consumption, and as a result, they lost 26% of their body weight in 21 days. In summary, MCD feeding suppresses SCD-1 in the liver, which likely contributes to hypermetabolism and weight loss. MCD feeding also induces hepatic steatosis, by an independent mechanism. Viewed together, these two disparate consequences of MCD feeding (weight loss and hepatic steatosis) give the appearance of an unusual form of lipodystrophy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|