Impaired intestinal free fatty acid transport followed by chylomicron malformation, not pancreatic insufficiency, cause metabolic defects in cystic fibrosis.

ABSTRACT: Intestinal disease is one of the earliest manifestations of cystic fibrosis (CF) in children and is closely tied to deficits in growth and nutrition, both of which are directly linked to future mortality. Patients are treated aggressively with pancreatic enzyme replacement therapy and a high-fat diet to circumvent fat malabsorption, but this does not reverse growth and nutritional defects. We hypothesized that defects in chylomicron production could explain why CF body weights and nutrition are so resistant to clinical treatments. We used gold standard intestinal lipid absorption and metabolism approaches, including mouse mesenteric lymph cannulation, in vivo chylomicron secretion kinetics, transmission electron microscopy, small intestinal organoids, and chylomicron metabolism assays to t

SUBMITTER: Teng L 

PROVIDER: S-EPMC11301217 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature