Impact of Intestinal Propionate Metabolism on Systemic Metabolic Homeostasis

Propionate is an abundant short-chain fatty acid in mammals, largely derived from gut microbiota production. Due to its abundance, propionate metabolism is essential to maintain systemic homeostasis. Inborn errors of essential metabolic enzymes in this pathway causes severe illness, such as the development of Propionic Acidemia in cases of Propionyl-CoA Carboxylase (PCC) deficiency. We and others have previously developed mouse models deficient in Pcca, encoding the alpha subunit of PCC, to study the systemic and liver-specific mechanisms of propionic acidemia. However, the role of PCC in the intestine, where propionate is primarily absorbed, is understudied. To investigate the gut-specific role of PCC, we developed a mouse knockout of Pcca using Villin-Cre (Pcca Vill) on a floxed Pcca (Pcca ff) background. Here, we demonstrate the phenotypes present in this model provided both a standard (chow) and high fat (HFD) diets.