Energetic cell sensors: a key to metabolic homeostasis

Recent breakthrough studies suggest that metabolic signals such as AMP/NAD+ and acetyl-CoA during fasting and feeding, respectively, translate the energetic cell status into specific transcriptional metabolic programs. Notably, NAD+ and acetyl-CoA modulate chromatin packaging and gene expression as substrates of histone deacetylases or histone acetyltransferases, respectively. These energetic sensors regulate circadian rhythms and their related physiological processes. In addition, NAD+ indirectly activates peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) during fasting, whereas acetyl-CoA inactivates PGC-1α upon feeding. In this review, we focus on recent evidence supporting the concept of an energetic code by which metabolic sensors control homeostasis during fasting and feeding and discuss its relevance to the pathophysiology of type 2 diabetes.