Apolipoprotein E isoforms disrupt long-chain fatty acid distribution in the plasma, the liver and the adipose tissue of mice

Abstract

Evidences suggest that omega-3 fatty acid (n-3 PUFA) metabolism is imbalanced in apolipoprotein E epsilon 4 isoform carriers (APOE4). This study aimed to investigate APOE genotype-dependant modulation of FA profiles, protein and enzyme important to fatty acid (FA) metabolism in the adipose tissue, the liver and the plasma using human APOE-targeted replacement mouse-model (N=37). FA transport (FATP) and binding (FABP) protein levels in tissues and concentrations of liver carnitine palmitoyltransferase 1 (CPT1) were performed. N-3 PUFA concentration was >45% lower in the adipose tissue and liver of APOE4 mice compared to APOE3 mice. In APOE4 mice, there were higher levels of FATP and FABP in the liver and higher FATP in the adipose tissue compared to APOE2 mice. There was a trend towards higher CPT1 concentrations in APOE4 mice compared to APOE3 mice. Therefore, since APOE-isoform differences were not always in line with the unbalanced n-3 PUFA profiles in organs, other proteins may be involved in maintaining n-3 PUFA homeostasis in mice with different APOE-isoforms.

Interaction between BMI and APOE genotype is associated with changes in the plasma long-chain–PUFA response to a fish-oil supplement in healthy participants

“…In line with this hypothesis, transgenic mice knock-in for the human APOE4 had higher FA transport proteins in the liver together with higher hepatic carnitine palmitoyl transferase 1 than did APOE3 mice (26). Carnitine palmitoyl transferase 1 is the rate-limiting enzyme for mitochondrial b-oxidation.…”

The effect of dietary fish oil on weight gain and insulin sensitivity is dependent onAPOEgenotype in humanized targeted replacement mice

“…This is unlikely to be attributed to greater activity in these mice, as physical activity—although contributing to daily energy expenditure—has no effect on total energy expenditure in mice housed below their thermoneutrality ( 32 ). Two recent studies indicated that in mice, the APOE4 genotype is associated with an increased basal mitochondrial uncoupling and fatty acid oxidation compared to the APOE3 genotype ( 11 , 33 ). LC n-3 PUFAs increase mitochondrial biosynthesis and oxidative capacity, as well as fatty acid oxidation ( 14 ).…”

Challenges to determining whether DHA can protect against age-related cognitive decline

“…The relationship between dietary Challenges to determining whether DHA can protect against age-related cognitive decline Review and plasma DHA therefore seems to shift in carriers of APOE4, who need higher dietary fish intakes to increase plasma DHA concentration [60]. In carriers of APOE4, β-oxidation may preferentially affect omega-3 PUFA compared with monounsaturated or saturated fatty acids, explaining the modification of DHA metabolism occurring with APOE4 [96,97].…”