APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524844/
As you can see below, our genotype yielded a higher HOMA-IR score with higher levels of C16:0, or palmitic acid. Palmitic acid can be found in full-fat dairy and red meat.Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype.
An interesting finding in the present analysis was the detrimental association between high plasma C16:0 on markers of insulin resistance, defined by HOMA-IR > 2.656, in E4 carriers. Although E4 carriers with low plasma C16:0 at baseline were not ‘insulin resistant’ (HOMA-IR, =2.35), those with high plasma C16:0 had a 31% greater HOMA-IR. This represents a novel finding and may suggest that E4 carriers with MetS are particularly sensitive to the detrimental metabolic effects of high palmitic acid (C16:0) levels. It is of note that increased plasma C16:0 has been associated with risk of type 2 diabetes, which could be in part due to increased insulin resistance57; our findings indicate that this relationship is amplified in E4 carriers. Previous studies have also shown a negative impact of diets rich in C16:0 and SFA on insulin sensitivity index (SI) in overweight individuals58, 59. However, several studies including the LIPGENE study, found no impact of reducing SFA on SI 29. The lack of effect found in the primary LIPGENE analysis highlights the importance of the APOE genotype (E4) on insulin-glucose homeostasis in metabolically challenged individuals.