Bile acid regulation of glucose metabolism

From LipidomicsWiki

De Fabiani et al. recently reports that bile acids inhibit PEPCK gene transcription and may regulate gluconeogenesis during fasting-fed cycle (De Fabiani et al. 2003). In response to fasting, glucagons and cAMP are increased to activate CREB, which induces PGC-1α expression and gluconeogenesis (Yoon et al. 2001). It appears that the same mechanism also regulate CYP7A1 gene transcription in fasted state. HNF4α and PGC-1α may coordinately regulate bile acid synthesis and gluconeogenesis. It is intriguing that bile acids are able to inhibit HNF4α interaction with CBP or PGC-1α. However, the mechanism of bile acid disruption of HNF4α interaction with these co-activators is unknown. Nevertheless, this finding suggests that bile acids may regulate glucose and energy metabolism in response to fasting. In Type I diabetes, the increase of bile acid synthesis may facilitate intestinal cholesterol absorption, which contributes to hypercholesterolemia, whereas the induction of gluconeogenesis contributes to hyperglycemia. In Type II diabetes with insulin resistance, CYP7A1 gene expression may be reduced and cholesterol accumulation may contribute to hypercholesterolemia. It has been reported that the control of lipid and glucose metabolism is tightly linked and activation of LXRα improve glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue (Lafitte et al. 2003). All these point to coordinate regulation of bile acid synthesis and glucose metabolism, at least during postabsorptive state and starvation.

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