title: Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion.
abstract: 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.
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands.
authors.forename: Frits
authors.initials: F
authors.lastname: Mattijssen
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands.
authors.forename: Sheril
authors.initials: S
authors.lastname: Alex
authors.affiliation: Human and Animal Physiology, Department of Animal Sciences, Wageningen University, 6700 EV Wageningen, The Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Swarts
authors.affiliation: Department of Pediatrics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.affiliation: Human and Animal Physiology, Department of Animal Sciences, Wageningen University, 6700 EV Wageningen, The Netherlands.
authors.forename: Evert M
authors.initials: EM
authors.lastname: van Schothorst
authors.affiliation: Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD Wageningen, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Kersten
keywords: Angptl4; Intestine; Obesity; Pancreatic lipase