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Tsc2, a positional candidate gene underlying a quantitative trait locus for hepatic steatosis[S]
- Source :
- Journal of Lipid Research, Vol 53, Iss 8, Pp 1493-1501 (2012)
- Publication Year :
- 2012
- Publisher :
- Elsevier, 2012.
-
Abstract
- Nonalchoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction and is associated with metabolic diseases, including obesity, insulin resistance, and type 2 diabetes. We mapped a quantitative trait locus (QTL) for NAFLD to chromosome 17 in a cross between C57BL/6 (B6) and BTBR mouse strains made genetically obese with the Lep(ob/ob) mutation. We identified Tsc2 as a gene underlying the chromosome 17 NAFLD QTL. Tsc2 functions as an inhibitor of mammalian target of rapamycin, which is involved in many physiological processes, including cell growth, proliferation, and metabolism. We found that Tsc2(+/-) mice have increased lipogenic gene expression in the liver in an insulin-dependent manner. The coding single nucleotide polymorphism between the B6 and BTBR strains leads to a change in the ability to inhibit the expression of lipogenic genes and de novo lipogenesis in AML12 cells and to promote the proliferation of Ins1 cells. This difference is due to a different affinity of binding to Tsc1, which affects the stability of Tsc2.
- Subjects :
- nonalcoholic fatty liver disease
congenital, hereditary, and neonatal diseases and abnormalities
Quantitative Trait Loci
Single-nucleotide polymorphism
fatty acid/metabolism
QD415-436
Biology
Quantitative trait locus
Biochemistry
Tuberous Sclerosis Complex 1 Protein
Mice
Endocrinology
Species Specificity
Non-alcoholic Fatty Liver Disease
Insulin-Secreting Cells
Tuberous Sclerosis Complex 2 Protein
Nonalcoholic fatty liver disease
medicine
Animals
genetics
Gene
triglycerides
Alleles
Research Articles
Genetics
Regulation of gene expression
diabetes
Lipogenesis
Tumor Suppressor Proteins
Fatty liver
Cell Biology
medicine.disease
Chromosomes, Mammalian
Fatty Liver
Chromosome 17 (human)
cell proliferation
Gene Expression Regulation
Liver
Sterol Regulatory Element Binding Protein 1
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 53
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....bf57a0bdecf038ce5192a8f43e4a3459