Diet-Gene Interactions and PUFA Metabolism: A Potential Contributor to Health Disparities and Human Diseases

Abstract

The “modern western” diet (MWD) has increased the onset and progression of chronic human diseases as qualitatively and quantitatively maladaptive dietary components give rise to obesity and destructive gene-diet interactions. There has been a three-fold increase in dietary levels of the omega-6 (n-6) 18 carbon (C18), polyunsaturated fatty acid (PUFA) linoleic acid (LA; 18:2n-6), with the addition of cooking oils and processed foods to the MWD. Intense debate has emerged regarding the impact of this increase on human health. Recent studies have uncovered population-related genetic variation in the LCPUFA biosynthetic pathway (especially within the fatty acid desaturase gene (FADS) cluster) that is associated with levels of circulating and tissue PUFAs and several biomarkers and clinical endpoints of cardiovascular disease (CVD). Importantly, populations of African descent have higher frequencies of variants associated with elevated levels of arachidonic acid (ARA), CVD biomarkers and disease endpoints. Additionally, nutrigenomic interactions between dietary n-6 PUFAs and variants in genes that encode for enzymes that mobilize and metabolize ARA to eicosanoids have been identified. These observations raise important questions of whether gene-PUFA interactions are differentially driving the risk of cardiovascular and other diseases in diverse populations, and contributing to health disparities, especially in African American populations.

Linoleic acid and the pathogenesis of obesity

“…In comparison, the expression of the IVS4 +869 G allele was associated with total fat and adiposity independent of lipid type in native black South African women [66]. Therefore, the particular genetic profiles of populations which are currently going through nutrition transitions has the ability to modulate the response to an increase in dietary LA [65], which is also of considerable further interest. It is also possible that the adipogenic properties of LA may be influenced by the macronutrient composition of a diet, with a study finding a high LA intake induced obesity in mice when incorporated into a predominately carbohydrate (sucrose) diet [67].…”

“…Adding further complexity to this area of research, there appear to be numerous genetic factors that influence the associations between different fatty acids and adiposity [65], with one study finding that an increase in the n-6:n-3 ratio in white South African women resulted in variable increases in adiposity, depending on IL-6 gene polymorphisms −174 G>C, IVS3 +281 G>T and IVS4 +869 A>G) [66]. In comparison, the expression of the IVS4 +869 G allele was associated with total fat and adiposity independent of lipid type in native black South African women [66].…”

Desaturase Activity Is Associated With Weight Status and Metabolic Risk Markers in Young Children

“…The underlying mechanisms are still not well understood. The relation of D6D and D5D with dyslipidemia may result from variations in the D6D and D5D encoding FADS1 and FADS2 gene cluster that has shown to be strongly associated with serum HDL and TG (23)(24)(25)(26). Elevated TG and low HDL in turn can lead to insulin resistance (27).…”

Efecto de los ácidos grasos poliinsaturados en la prevención de la obesidad a través de modificaciones epigenéticas

“…Así, Niculescu et al 74 han podido demostrar la asociación entre la disponibilidad de ácido ␣-linolénico (ALA; suplementación de 75.367 nmol/mg/día) durante la gestación y la lactancia en ratones, y alteraciones en la metilación del ADN del gen FADS2 (en inglés, fatty acid desaturase 2) y del intrón número 1 en los hígados de las madres y los hijos al final del período de lactancia. FADS2 es una enzima desaturasa que cataliza diferentes pasos en la ruta de biosíntesis de los AGPI de cadena larga, a partir de ácido linoleico (n-6) y ALA 75 . Además, este estudio indica que la interacción materna con ALA durante la gestación y lactancia podría alterar diferencialmente el metabolismo de n-3 y n-6 74 .…”