Fabp1 gene ablation inhibits high‐fat diet‐induced increase in brain endocannabinoids

Abstract

The endocannabinoid system shifts energy balance toward storage and fat accumulation, especially in the context of diet-induced obesity. Relatively little is known about factors outside the central nervous system that may mediate the effect of high fat diet (HFD) on brain endocannabinoid levels. One candidate is the liver fatty acid binding protein (FABP1), a cytosolic protein highly prevalent in liver, but not detected in brain, which facilitates hepatic clearance of fatty acids. The impact of Fabp1 gene ablation (LKO) on the effect of high-fat diet (HFD) on brain and plasma endocannabinoid levels was examined and data expressed for each parameter as the ratio of high fat diet/control diet. In male wild-type mice, HFD markedly increased brain N-acylethanolamides, but not 2-monoacylglycerols. LKO blocked these effects of HFD in male mice. In female wild-type mice, HFD slightly decreased or did not alter these endocannabinoids as compared with male wild-type. LKO did not block the HFD effects in female mice. The HFD-induced increase in brain arachidonic acid -derived arachidonoylethanolamide in males correlated with increased brain free and total arachidonic acid. The ability of LKO to block the HFD-induced increase in brain arachidonoylethanolamide correlated with reduced ability of HFD to increase brain free and total arachidonic acid in males. In females, brain free and total arachidonic acid levels were much less affected by either HFD or LKO in the context of HFD. These data showed that LKO markedly diminished the impact of HFD on brain endocannabinoid levels, especially in male mice.

Ablating both Fabp1 and Scp2/Scpx (TKO) induces hepatic phospholipid and cholesterol accumulation in high fat-fed mice

“…Mice were acclimated for 1 week on a defined, 10 kcal% fat control chow (#D12450B, Research Diets, New Brunswick, NJ) known to be free of phytol and phytoestrogen. Phytol and phytoestrogen were avoided because they may impact sex differences and FABP1 expression as described earlier [62]. In each group of 16 individually-housed mice, 8 mice were continued an additional 12 weeks on this same defined diet while the other 8 mice were pair-fed based upon food weight an isocaloric high fat diet (HFD, # D12451, Research Diets, New Brunswick, NJ).…”

“…However, despite the fact that NAFLD is more prevalent in women [23,24], most HFD-induced rodent models of NAFLD have focused only on males fed HFD ad libitum (rev. in [62]. Under ad libitum feeding conditions, such male rodents strongly prefer and eat more HFD as compared to normal chow (rev.…”

“…Under ad libitum feeding conditions, such male rodents strongly prefer and eat more HFD as compared to normal chow (rev. in [62]. Thus, there is a need for controlled, pair-fed HFD studies not only of male but even more so female rodents to study sexual dimorphism of NAFLD independent of increased total intake of HFD.…”

FABP1 knockdown in human enterocytes impairs proliferation and alters lipid metabolism

“…A direct comparison of Fabp2 −/− and Fabp1 −/− mice fed high fat diets also suggested that the two enterocyte proteins play different roles in intestinal and systemic metabolism [18]. Recent works indicate that Fabp1 −/− mice shows impaired endocannabinoid system both in liver and in the brain [23,24]. …”

Sterol Carrier Protein‐2/Sterol Carrier Protein‐x/Fatty Acid Binding Protein‐1 Ablation Impacts Response of Brain Endocannabinoid to High‐Fat Diet

“…The brain does not express FABP1 (Avdulov et al, ; Myers‐Payne et al, ; Owada et al, ). Nevertheless, ablation of the Fabp1 gene (LKO) in male mice dramatically increased brain AEA and 2‐AG (Martin et al, , ). Interestingly, in females, the brain AEA and 2‐AG levels are less impacted by LKO—likely due to their much lower basal level of FABP1 and potentially also due to the selective LKO‐induced reduction in brain SCP‐2 level in females (Martin et al, , b).…”