title: Direct comparison of mice null for liver or intestinal fatty acid-binding proteins reveals highly divergent phenotypic responses to high fat feeding.
abstract: The enterocyte expresses two fatty acid-binding proteins (FABP), intestinal FABP (IFABP; FABP2) and liver FABP (LFABP; FABP1). LFABP is also expressed in liver. Despite ligand transport and binding differences, it has remained uncertain whether these intestinally coexpressed proteins, which both bind long chain fatty acids (FA), are functionally distinct. Here, we directly compared IFABP(-/-) and LFABP(-/-) mice fed high fat diets containing long chain saturated or unsaturated fatty acids, reasoning that providing an abundance of dietary lipid would reveal unique functional properties. The results showed that mucosal lipid metabolism was indeed differentially modified, with significant decreases in FA incorporation into triacylglycerol (TG) relative to phospholipid (PL) in IFABP(-/-) mice, whereas LFABP(-/-) mice had reduced monoacylglycerol incorporation in TG relative to PL, as well as reduced FA oxidation. Interestingly, striking differences were found in whole body energy homeostasis; LFABP(-/-) mice fed high fat diets became obese relative to WT, whereas IFABP(-/-) mice displayed an opposite, lean phenotype. Fuel utilization followed adiposity, with LFABP(-/-) mice preferentially utilizing lipids, and IFABP(-/-) mice preferentially metabolizing carbohydrate for energy production. Changes in body weight and fat may arise, in part, from altered food intake; mucosal levels of the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamine were elevated in LFABP(-/-), perhaps contributing to increased energy intake. This direct comparison provides evidence that LFABP and IFABP have distinct roles in intestinal lipid metabolism; differential intracellular functions in intestine and in liver, for LFABP(-/-) mice, result in divergent downstream effects at the systemic level.
authors.affiliation: From the Department of Nutritional Sciences and; the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Gajda
authors.affiliation: From the Department of Nutritional Sciences and.
authors.forename: Yin Xiu
authors.initials: YX
authors.lastname: Zhou
authors.affiliation: the School of Dietetics and Human Nutrition, McGill University, Montréal, Québec H9X 3V9, Canada, and.
authors.forename: Luis B
authors.initials: LB
authors.lastname: Agellon
authors.affiliation: the Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Fried
authors.affiliation: From the Department of Nutritional Sciences and.
authors.forename: Sarala
authors.initials: S
authors.lastname: Kodukula
authors.affiliation: From the Department of Nutritional Sciences and.
authors.forename: Walter
authors.initials: W
authors.lastname: Fortson
authors.affiliation: From the Department of Nutritional Sciences and.
authors.forename: Khamoshi
authors.initials: K
authors.lastname: Patel
authors.affiliation: From the Department of Nutritional Sciences and; the Rutgers Center for Lipid Research, Rutgers University, New Brunswick, New Jersey 08901,. Electronic address: Storch@aesop.rutgers.edu.
authors.forename: Judith
authors.initials: J
authors.lastname: Storch
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*
chemical_list: D004041:Dietary Fats; C493320:Fabp1 protein, mouse; C493405:Fabp2 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D010743:Phospholipids; D014280:Triglycerides
keywords: Fatty Acid; Fatty Acid-binding Protein; Intestine; Lipid Metabolism; Monoacylglycerol