Intestinal lipid metabolism regulates absorption and surface of gut epithelium
Intestinal surface changes in size and function in response to environmental conditions, but what propels these alterations and what are the metabolic consequences is not clear. Here we show that in mice gut surface enlarges by increasing food amount rather than caloric intake, contributing to an increased absorptive function, and that it can be reversed by reducing daily food amount. Genetic- and environment-induced gut enlargement due to overeating is principally supported by upregulation of the intestinal lipid metabolism and transport. Intestinal knock-out, and pharmacological inhibition of PPARa supress intestinal crypt formation and shorten villi in the small intestine of mice and in human intestinal biopsies, respectively, and diminish post-prandial triglyceride transport and nutrient uptake. PPARa inhibition limits lipid absorption and restricts lipid droplet growth and PLIN2 levels, critical for the droplet formation. This improves lipid metabolism, reduces body adiposity and liver steatosis, suggesting an alternative target for treating obesity. Overall design: Examination of 2 different histone modifications in Neural progenitor cells.