Abstract 14939: Deficiency of Fatty Acid Binding Protein-4 and -5 Impairs Intestinal Lipid Absorption
Introduction: Fatty acid binding protein 4 (FABP-4) and FABP-5 are cytosolic FA chaperones that mediate metabolic disorders such as diet-induced obesity, diabetes and atherosclerosis. We recently showed that FABP4/5 expressed in capillary endothelial cells facilitate FA uptake from circulation into interstitial fluid. However, serum levels of free FA (FFA) and triacylglycerol (TG) were not elevated in mice lacking both FABP4/5 (double knockout: DKO) compared with wild-type (WT) during feeding despite the fact that FA uptake by the heart and skeletal muscle was significantly reduced in DKO mice.
Hypothesis: FABP4/5 also play a role in lipid absorption.
Results: Under high fat diet for six weeks as well as ketogenic diet with no carbohydrate for three days, serum TG levels were significantly lower in DKO mice compared to WT, suggesting reduced lipid absorption during long term lipid overload. We next examined an effect of acute lipid overload by olive oil gavage (10 μl/g body weight). Serum TG levels were significantly lower in DKO mice at 2, 4 and 6 hours after olive oil gavage, which was accompanied by reduced levels of TG-rich lipoproteins, chylomicron and very large density lipoprotein, as well as TG levels in intestinal lymph. Lower levels of TG by olive oil gavage were confirmed in DKO mice even when TG consumption by peripheral tissues was blocked by intravenous injection of tyloxapol, an inhibitor of lipoprotein lipase. Furthermore, TG accumulation in proximal small intestine was diminished, suggesting that lipid absorption may be inhibited at levels of FA uptake and/or TG formation. Consistent with this, expression level of diacylglycerol acyl-transferase 2, a gene involved in TG formation, was decreased. Curiously enough, immunohistochemistry revealed that FABP4/5 were expressed in capillary endothelial cells in villi of small intestine, but not lymph vessel, where TG-rich chyromicron is secreted, suggesting that FABP4/5 play a role in intestinal lipid absorption through unexpected mechanism.
Conclusions: Lipid absorption is impaired in DKO mice, and raise the possibility that protection of DKO mice from high fat diet-induces metabolic abnormalities is at least partly ascribed to disturbance of lipid absorption.
Author Disclosures: M.R. Syamsunarno: None. T. Iso: None. M. Kurabayashi: None.
- © 2014 by American Heart Association, Inc.