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Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c
- Source :
- Diabetes, Obesity and Metabolism; Vol 12
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- Steatosis is an accumulation of triglycerides in the liver. Although an excessive availability of plasma fatty acids is an important determinant of steatosis, lipid synthesis from glucose (lipogenesis) is now also considered as an important contributing factor. Lipogenesis is an insulin- and glucose-dependent process that is under the control of specific transcription factors, sterol regulatory element binding protein 1c (SREBP-1c), activated by insulin and carbohydrate response element binding protein (ChREBP) activated by glucose. Insulin induces the maturation of SREBP-1c by a proteolytic mechanism initiated in the endoplasmic reticulum (ER). SREBP-1c in turn activates glycolytic gene expression, allowing glucose metabolism, and lipogenic genes in conjunction with ChREBP. Lipogenesis activation in the liver of obese markedly insulin-resistant steatotic rodents is then paradoxical. Recent data suggest that the activation of SREBP-1c and thus of lipogenesis is secondary in the steatotic liver to an ER stress. The ER stress activates the cleavage of SREBP-1c independent of insulin, thus explaining the paradoxical stimulation of lipogenesis in an insulin-resistant liver. Inhibition of the ER stress in obese rodents decreases SREBP-1c activation and lipogenesis and improves markedly hepatic steatosis and insulin sensitivity. ER is thus a new partner in steatosis and metabolic syndrome which is worth considering as a potential therapeutic target.
- Subjects :
- medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Carbohydrate metabolism
Biology
Endoplasmic Reticulum
Gene Expression Regulation, Enzymologic
Mice
03 medical and health sciences
0302 clinical medicine
Endocrinology
Insulin resistance
Internal medicine
Internal Medicine
medicine
Animals
Homeostasis
Humans
Carbohydrate-responsive element-binding protein
030304 developmental biology
0303 health sciences
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
Lipogenesis
Insulin
Fatty liver
medicine.disease
Fatty Liver
030220 oncology & carcinogenesis
Unfolded protein response
Insulin Resistance
Steatosis
Sterol Regulatory Element Binding Protein 1
Transcription Factors
Subjects
Details
- ISSN :
- 14628902
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Diabetes, Obesity and Metabolism
- Accession number :
- edsair.doi.dedup.....3c0717b751755e156338076a05892b5f