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Diabetes & Metabolism
Volume 34, n° 6P2
pages 643-648 (décembre 2008)
Doi : 10.1016/S1262-3636(08)74599-3
The role of the lipogenic pathway in the development of hepatic steatosis
Rôle de la lipogenèse dans le développement de la stéatose hépatique
 

Fig. 1.




Fig. 1. : 

Transcriptional control of glycolysis and lipogenesis. The conversion of glucose into fatty acids through de novo lipogenesis is nutritionally regulated, and both glucose and insulin signaling pathways are elicited in response to dietary carbohydrates to synergistically induce glycolytic and lipogenic gene expression. The nature of the glucosesignaling compound was recently identified as the transcription factor ChREBP (carbohydrate responsive element-binding protein). Glucose activates ChREBP by stimulating its gene expression and mediating its post-translational modification(s). ChREBP is required for the induction of L-PK, which is exclusively dependent on glucose. Induction of lipogenic genes, such as ACC, FAS, SCD-1, is under the combined actions of ChREBP and SREBP-1c. Transcription factor SREBP-1c also mediates the effect of insulin on GPAT, although the direct action of ChREBP on GPAT gene expression has not been established. As the nuclear receptor LXR is required for insulin action on SREBP-1c expression, insulin must, in some manner, stimulate the production of an endogenous sterol ligand of LXR (oxysterols). ChREBP is also a direct target of LXR when activated by pharmacological agonists such as T0-901317, but LXR is unable to activate ChREBP expression in response to glucose (Adapted from Robichon et al . [54]).


Fig. 2.




Fig. 2. : 

Role of the lipogenic pathway in the development of hepatic steatosis. Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver dysfunction, and its incidence has increased markedly over the years. While the mechanisms involved in the pathogenesis of NAFLD in humans have not been thoroughly investigated, enhanced activity of the lipogenic pathway very likely contributes to the development of hepatic steatosis in NAFLD. In response to insulin and glucose, sterol regulatory element-binding protein (SREBP)-1c and carbohydrate responsive element-binding protein (ChREBP) are activated, respectively, and induce the expression of lipogenic genes, including ACC, FAS and SCD1. SREBP-1c and ChREBP are also transactivated by the nuclear receptor LXR that regulates the metabolism of cholesterol and fatty acids. More knowledge of the respective roles of these transcription factors in the pathogenesis of NAFLD is now needed.

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