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 [ 3 H]TG uptake compared with wild-type littermates. cd36 ؊ / ؊ mice showed a 2-fold enhanced postprandial TG response upon an intragastric fat load ( P Ͻ 0.05), with a concomitant 2.5-fold increased FFA response ( P Ͻ 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 Ͻ 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[ 3 H]oleate-labeled VLDL-like emulsion particles by 2.5-fold ( P Ͻ 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. is abundant in peripheral tissues active in FFA metabolism, such as adipose tissue, skeletal muscle, and cardiac muscle, where it is involved in high-affinity uptake of FFA (1, 6, 7). To directly investigate a role for CD36 in lipid metabolism, mice lacking CD36 were generated by gene targeting (8). These CD36-deficient ( cd36 Ϫ / Ϫ ) mice exhibited increased plasma FFA and triglyceride (TG) levels (8). Coburn et al. (9) showed that FFA uptake was considerably impaired in muscle and adipose tissue of cd36 Ϫ / Ϫ mice. Febbraio et al. (8) further showed that the increase in plasma TG levels in the absence of CD36 was primarily attributable to an increase in VLDL-sized particles. Although these data suggest a role for CD36 in TG metabolism in addition to FFA metabolism, the exact mechanisms underlying the increased TG levels in cd36 Ϫ / Ϫ mice are unknown. It has been discussed by Hajri et al. (10) that the VLDL production rate may be enhanced in cd36 Ϫ / Ϫ mice, but the increased plasma TG levels may also be attributable to increased intestinal lipid absorption or to decreased LPL-mediated TG clearance from the circulation.Therefore, the aim of the present study was to elucidate the cause of the hypertriglyceridemia in cd36 Ϫ / Ϫ mice in vivo. Our results show that the increased plasma TG levels in cd36 Ϫ / Ϫ mice are caused by a decreased TG hydrolysis rate rather than by differences in the production of hepatic VLDL-TG or intestinal lipid absorption. From the present study, we conclude that the hypertriglyceridemia observed in cd36 Ϫ / Ϫ mice is caused by decreased LPLmediated hydrolysis of TG-rich lipoproteins resulting ...

CD36 Is Important for Chylomicron Formation and Secretion and May Mediate Cholesterol Uptake in the Proximal Intestine

“…Our studies, however, do not agree well with those of Goudriaan et al 23,31 Using an inhibitor of intravascular lipolysis, Triton WR1339, they showed that CD36 KO and WT mice were comparable in the plasma recovery of infused TG and FA. We cannot explain the discrepancy between their findings and ours, but it should be noted that their plasma TG recovery was only about 15% of the total infused by the end of 4 hours as compared with our lymphatic recoveries of about 44% of the total infused for WT and 18% for the KO animals.…”

Association of CD36 expression and polymorphism with serum biochemical indices in Cherry Valley duck

“…Correlation analysis revealed that CD36 was positively correlated with LDL, which is similar to the findings of previous studies (Yamashita et al, 2007;Xie et al, 2011;Babaahmadi Rezaei et al, 2013). Goudriaan et al (2005) observed an increase in TG levels in CD36 knockout mice, similar to the results of the present study. These findings indicate that lipoprotein is regulated by the level of CD36 gene and protein expression, which subsequently affects cellular cholesterol levels.…”

Gene Expression Profiling of Rat Liver Treated With Serum Triglyceride-Decreasing Compounds

“…Moreover, it has been reported that CD36 plays a role in plasma TG homeostasis via modulation of LPL activity (Goudriaan et al, 2005). Thus, an increase of this gene expression would be one of the mechanisms of plasma TG level decrease in the corresponding animal.…”