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Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2002 May 31; Vol. 277 (22), pp. 19353-7. Date of Electronic Publication: 2002 Mar 28. - Publication Year :
- 2002
-
Abstract
- Obesity is a common nutritional problem often associated with diabetes, insulin resistance, and fatty liver (excess fat deposition in liver). Leptin-deficient Lep(ob)/Lep(ob) mice develop obesity and those obesity-related syndromes. Increased lipogenesis in both liver and adipose tissue of these mice has been suggested. We have previously shown that the transcription factor sterol regulatory element-binding protein-1 (SREBP-1) plays a crucial role in the regulation of lipogenesis in vivo. To explore the possible involvement of SREBP-1 in the pathogenesis of obesity and its related syndromes, we generated mice deficient in both leptin and SREBP-1. In doubly mutant Lep(ob/ob) x Srebp-1(-/-) mice, fatty livers were markedly attenuated, but obesity and insulin resistance remained persistent. The mRNA levels of lipogenic enzymes such as fatty acid synthase were proportional to triglyceride accumulation in liver. In contrast, the mRNA abundance of SREBP-1 and lipogenic enzymes in the adipose tissue of Lep(ob)/Lep(ob) mice was profoundly decreased despite sustained fat, which could explain why the SREBP-1 disruption had little effect on obesity. In conclusion, SREBP-1 regulation of lipogenesis is highly involved in the development of fatty livers but does not seem to be a determinant of obesity in Lep(ob)/Lep(ob) mice.
- Subjects :
- Adipose Tissue metabolism
Animals
Blotting, Northern
Crosses, Genetic
Genotype
Leptin biosynthesis
Lipid Metabolism
Lipoprotein Lipase biosynthesis
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
RNA, Messenger metabolism
Sterol Regulatory Element Binding Protein 1
Triglycerides metabolism
CCAAT-Enhancer-Binding Proteins genetics
CCAAT-Enhancer-Binding Proteins physiology
DNA-Binding Proteins genetics
DNA-Binding Proteins physiology
Fatty Liver therapy
Insulin Resistance genetics
Liver metabolism
Obesity genetics
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 277
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11923308
- Full Text :
- https://doi.org/10.1074/jbc.M201584200