Endocrine Abstracts

Introduction: Adipocyte fatty acid binding protein (A-FABP) is a fatty acid chaperone that facilitates the efflux of free fatty acid from cytoplasm into circulation. Previous studies show that A-FABP knockout (KO) mice are more susceptible to diet-induced obesity comparing to wild type (WT) littermates. Here we investigate the underlying mechanism of A-FABP in the regulation of diet-induced obesity.

Methods: A-FABP KO mice and their WT littermates were fed on either standard chow (STC) or high fat high cholesterol (HFHC) diet for 24 weeks. Energy expenditure and cold challenge study were performed to evaluate the ability of thermoregulation of mice. Fatty acid transportation rate in adipocytes of WT and A-FABP KO mice was determined by fluorescence and radiation method.

Results: A-FABP expression in BAT and its circulating level are significantly elevated in WT mice in response to HFHC diet induction and acute cold exposure. Oxygen consumption was significantly lower in HFHC diet-induced A-FABP KO mice, and they are cold intolerant while STC-fed A-FABP KO mice show better thermoregulation comparing to their relative WT controls. Basal UCP-1 expression in BAT is significantly higher in A-FABP KO mice when compared to WT mice under STC. However, both HFHC diet- and cold-induced up-regulation of UCP-1 expression are impaired in A-FABP KO mice. The uptake and efflux rate in adipocytes of A-FABP KO mice are significantly lower comparing to their WT controls.

Conclusion: These data suggest that A-FABP is a potential regulator of adaptive thermogenesis, facilitating the FFA transportation from white adipocyte to brown adipocyte for β-oxidation to generate more heat to combat excess weight gain. The up-regulation of basal UCP-1 expression in BAT of A-FABP KO mice may be a compensatory mechanism for maintaining energy homeostasis.