Figure. Protective Fasting Metabolic Programs.

In response to fasting, Peroxisome Proliferator Activated Receptor Alpha (PPARa), co-activated by Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1a) mediates the upregulation of ketogenic and fatty acid oxidation gene programs. PPARa also regulates the induction of hepatic Fibroblast Growth Factor 21 (FGF21) expression during fasting. Adenosine monophosphate activated protein kinase (AMPK) activation will promote autophagy which is inhibited by mechanistic target of rapamycin (mTOR). PPARa, PGC1a and autophagy are all implicated as protective pathways that limit acute kidney injury (AKI). These protective fasting metabolic programs are suppressed by glucose and insulin activated pathways, suggesting a need to re-evaluate current nutrient and metabolic approaches that may lead to excessive glucose, and thus obligate insulin exposures in patients with sepsis and at risk for AKI.