Fatty acid transport protein 4 is dispensable for intestinal lipid absorption in mice

Area of Science:

• Lipid metabolism
• Molecular biology
• Gastroenterology

Background:

• Fatty acid transport protein 4 (FATP4) is a proposed key transporter in intestinal lipid absorption.
• Genetic deletion of FATP4 leads to perinatal lethality due to skin defects, necessitating rescue models.

Purpose of the Study:

• To investigate the specific role of intestinal FATP4 in dietary lipid absorption using a genetically modified mouse model.
• To determine if FATP4 influences triglyceride and cholesterol absorption, as well as overall lipid homeostasis.

Main Methods:

• Generation of Fatp4(-/-);Ivl-Fatp4(tg/+) mice with rescued skin phenotype to study intestinal FATP4 function.
• Comparison of food intake, growth, weight gain, intestinal triglyceride absorption, and fecal fat excretion between mutant and wild-type mice on different diets.
• Analysis of enterocyte lipid content, serum cholesterol, hepatic lipid content, and VLDL secretion.

Main Results:

• No significant differences in food consumption, growth, weight gain, or intestinal triglyceride absorption between FATP4-rescued mice and wild-type littermates.
• Increased enterocyte triglyceride and fatty acid content in FATP4-rescued mice on a high-fat diet, without compensatory changes in other transporters.
• Lower serum cholesterol in FATP4-rescued mice, but no differences in hepatic VLDL secretion or lipid content.

Conclusions:

• Intestinal FATP4 does not appear to have a significant physiological role in the absorption of dietary lipids in mice.
• The study provides evidence against FATP4 being a major determinant of intestinal lipid absorption under the tested conditions.