The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP‐1c
Open accessAbstract
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.
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“A similar selective effect of rapamycin was found in livers of rats and mice submitted to a fasting-refeeding protocol [27].”
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Pawlak, M., Lefebvre, P., & Staels, B. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.039 · Cited by 1,578
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Hyperinsulinemia Drives Diet-Induced Obesity Independently of Brain Insulin Production
Mehran, A. E., Templeman, N. M., Brigidi, G. S., Lim, G. E., Chu, K.-Y., Hu, X., Botezelli, J. D., Asadi, A., Hoffman, B. G., Kieffer, T. J., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.10.019 · Cited by 498
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Metadata
- Authors
- Ferré, P., & Foufelle, F.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2010-10
- Volume
- 12
- Issue
- s2
- Pages
- 83-92
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2091330563
- Cited by
- 704
- References
- 8
- FWCI
- 19.29
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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