Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes.

These are interesting findings that may provide a new connection between glucose and lipid metabolism.

CYP7A1 is the key regulator of hepatic bile acid synthesis. In this interesting paper, the authors studied the regulation of this gene by glucose via AMPK and HNF4alpha. More importantly, glucose-dependent regulation of CYP7A1 expression apparently involves epigenetic regulation by stimulating histone acetyltransferase activity and inhibiting methyltransferase-mediated methylation of epigenetic marks in the promoter region of this gene. So far, it was believed that transcription factor FXR, activated by bile acids itself, was the main (negative) regulator of CYP7A1 expression. The connection between glucose- and bile acid-regulated expression of CYP7A1 shows once more that there is a narrow connection between glucose and lipid metabolism in general. This interconnection has now been found and studied in liver cells, but is probably not restricted to the liver. Future research should also focus on other organs in which glucose and lipid metabolism are both of importance, such as intestine and muscle.

Unfortunately, this paper only performed in vitro studies using HEPG2 cells and human hepatocytes to prove the glucose-stimulated expression of CYP7A1. Evidence for an interaction between glucose and lipid metabolism would even be stronger if similar regulation could be found in in vivo models. Nevertheless, these findings may point to an important basic principle that is relevant for a better understanding of health and the development of various metabolic disorders.