Key result
Chronic high-fat diet slows postprandial triglyceride absorption independently of intestinal ANGPTL4 in mice.
Why the study?
Intestinal ANGPTL4 was suggested to inhibit pancreatic lipase, prompting the hypothesis that high-fat diet-induced ANGPTL4 would reduce postprandial triglyceride absorption.
Chronic high-fat feeding reduces postprandial triglyceride absorption in mice, but contrary to previous hypotheses, this mechanism is independent of intestinal ANGPTL4.
High-fat diet reduces postprandial triglyceride absorption independently of intestinal ANGPTL4 in mice; challenges prior mechanistic hypotheses and leaves alternative pathways open for study.
Pancreatic lipase is the major enzyme responsible for breaking down dietary triglycerides in the intestines. A previous report suggested that intestinal angiopoietin-like 4 (ANGPTL4) might serve as an endogenous inhibitor of pancreatic lipase and thus regulate fat absorption. As ANGPTL4 expression is reportedly induced by high-fat-diet feeding, we hypothesized that induction of ANGPTL4 by a high-fat diet would lead to an increased inhibition of pancreatic lipase, less breakdown of dietary triglycerides, and ultimately a reduced rate of postprandial triglyceride absorption. To test this hypothesis, we generated intestinal epithelial cell-specific ANGPTL4 knockout mice, fed them diets with varying levels of fat, and measured postprandial triglyceride absorption and intestinal triglyceride lipase activity. As we hypothesized, we found that chronic high-fat feeding reduced the rate of postprandial triglyceride absorption in mice. However, this regulation of postprandial triglyceride absorption appeared to be largely independent of ANGPTL4, as similar decreases were observed in both wild-type and intestinal epithelial cell-specific ANGPTL4 knockout mice. We conclude that there is mechanism by which chronic high-fat feeding reduces the rate of secretion of dietary triglycerides into the circulation, but that this mechanism does not require intestinal ANGPTL4.
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Shetty et al. (2026) studied Hypertriglyceridemia / Obesity (Animal Model). Intestinal epithelial cell-specific ANGPTL4 knockout and High-fat diet vs. Wild-type littermates and normal chow diet was evaluated on Rate of postprandial triglyceride absorption. Chronic high-fat diet feeding significantly reduced the rate of postprandial triglyceride absorption in mice, but this reduction occurred independently of intestinal epithelial cell ANGPTL4.
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