Refining sugar's involvement in cholesterol synthesis.

Glucose metabolism and cholesterol synthesis are often regarded in isolation. Increasing evidence not only links these pathways but also suggests glucose catabolism regulates cholesterol synthesis. Uptake of glucose increases cholesterol production. However, the precise mechanism by which this occurs is not fully understood and is likely to involve many aspects of cellular pathways participating in energy sensing, cholesterol regulation, and synthesis. Here, we review some interesting links between cholesterol synthesis and glucose metabolism. Given glucose breakdown produces energy (both via glycolysis and its products through oxidative phosphorylation), and considering cholesterol synthesis is an energetically demanding process, it would seem logical that glucose metabolism impacts cholesterol synthesis. The energy sensing kinase AMPK carefully monitors energy supply to induce or suppress cholesterol synthesis as needed. Akt, activated by the insulin signalling cascade, regulates key transcription factors involved in lipid metabolism. The insulin signalling pathway also activates machinery involved in the deubiquitination of a key cholesterol synthesis enzyme. Moreover, glucose metabolites, acetyl-CoA, and GlcNAc are substrates for protein acetylation and N-glycosylation, respectively, and can stabilise proteins involved in cholesterol synthesis. As glucose and cholesterol dysregulation are both associated with numerous diseases, understanding the mechanisms of how glucose metabolism and cholesterol synthesis intersect may offer new avenues for therapeutics that make use of these findings.