CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance

Abstract

CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36−/−) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36−/− mice. cd36−/− mice showed no differences in hepatic VLDL-TG production or intestinal [3H]TG uptake compared with wild-type littermates. cd36−/− mice showed a 2-fold enhanced postprandial TG response upon an intragastric fat load (P < 0.05), with a concomitant 2.5-fold increased FFA response (P < 0.05), suggesting that the increased FFA in cd36−/− mice may impair LPL-mediated TG hydrolysis. Postheparin LPL levels were not affected. However, the in vitro LPL-mediated TG hydrolysis rate as induced by postheparin plasma of cd36−/− mice in the absence of excess FFA-free BSA was reduced 2-fold compared with wild-type plasma (P < 0.05). This inhibition was relieved upon the addition of excess FFA-free BSA. Likewise, increasing plasma FFA in wild-type mice to the levels observed in cd36−/− mice by infusion prolonged the plasma half-life of glycerol tri[3H]oleate-labeled VLDL-like emulsion particles by 2.5-fold (P < 0.05).We conclude that the increased plasma TG levels observed in cd36−/− mice are caused by decreased LPL-mediated hydrolysis of TG-rich lipoproteins resulting from FFA-induced product inhibition of LPL.

Keywords

• free fatty acids
• fatty acid transport
• postprandial lipid metabolism
• transgenic mice
• triglyceride hydrolysis