Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion by inhibiting pancreatic lipase, and its deletion in mice leads to increased fat mass and body weight.
Angptl4 acts as an endogenous inhibitor of intestinal pancreatic lipase, revealing a novel feedback mechanism that regulates dietary lipid digestion and may protect against lipid overload.
Dietary triglycerides are hydrolyzed in the small intestine principally by pancreatic lipase. Following uptake by enterocytes and secretion as chylomicrons, dietary lipids are cleared from the bloodstream via lipoprotein lipase. Whereas lipoprotein lipase is inhibited by several proteins including Angiopoietin-like 4 (Angptl4), no endogenous regulator of pancreatic lipase has yet been identified. Here we present evidence that Angptl4 is an endogenous inhibitor of dietary lipid digestion. Angptl4-/- mice were heavier compared to their wild-type counterparts without any difference in food intake, energy expenditure or locomotor activity. However, Angptl4-/- mice showed decreased lipid content in the stools and increased accumulation of dietary triglycerides in the small intestine, which coincided with elevated luminal lipase activity in Angptl4-/- mice. Furthermore, recombinant Angptl4 reduced the activity of pancreatic lipase as well as the lipase activity in human ileostomy output. In conclusion, our data suggest that Angptl4 is an endogenous inhibitor of intestinal lipase activity.
Mattijssen et al. (2013) studied Lipid digestion. Angptl4 deficiency vs. Wild-type was evaluated on Intestinal lipid digestion and body weight. Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion by inhibiting pancreatic lipase, and its deletion in mice leads to increased fat mass and body weight.