Gene–PUFA interactions and obesity risk

Abstract

Although there are indications for modulatory effects of PUFA on associations between SNP and obesity risk, scientific evidence in human subjects is still scarce. The present analyses investigated interaction effects between SNP in candidate genes for obesity and PUFA in erythrocyte membranes on obesity risk. Within the second Bavarian Food Consumption Survey (cross-sectional, population-based), 568 adults provided blood samples. Fatty acid composition of erythrocyte membranes was analysed by means of GC. Genotyping was performed for twenty-one genes, including cytokines, adipokines, neurotransmitters and transcription factors. In addition, plasma IL-6 concentrations were analysed. For the statistical analysis, a logistic regression model assuming additive genetic effects was chosen. About 20 % of the study participants were classified as obese (BMI $30 kg/m 2 ). Several significant gene -PUFA interactions were found, indicating regulatory effects of PUFA by gene variants of IL-2, IL-6, IL-18, TNF receptor family member 1B and 21, leptin receptor and adiponectin on obesity risk. After stratification by genotype, the strongest effects were found for rs2069779 (IL-2) and all tested PUFA as well as for rs1800795 (IL-6) and linoleic or arachidonic acid. The obesity risk of minor allele carriers significantly decreased with increasing fatty acid content. The genetic PUFA -IL-6 interaction was also reflected in plasma IL-6 concentrations. If replicated in a prospective study with sufficient statistical power, the results would indicate a beneficial effect of high PUFA supply for a substantial proportion of the population with respect to obesity risk.Key words: Obesity: Gene -PUFA interactions: Nutritional biomarkers: Bavarian Food Consumption Survey II Obesity is a multifactorial disorder reflecting complex interactions of genes, environment and lifestyle (1) . Industrialisation and modernisation encourage a sedentary lifestyle with concomitantly increased energy intake, resulting in an imbalance of energy intake and expenditure (2) and consequently in gaining surplus weight. About 40 -70 % of the variance in the BMI is accounted for by genetic factors as several studies of twins, adoptees and families have shown (3 -5) . Screenings of candidate regions as well as genome-wide scans have helped to identify SNP that increase the risk of becoming overweight or obese (6) .There is considerable evidence that not all fatty acids are obesogenic (7) . Approximately 6·2-7·4 % of our average daily energy intake is accounted for by PUFA (n-3 PUFA 0·7-0·9 %; n-6 PUFA 5·5-6·5 %) (8) . PUFA exert their influence on cardiovascular function, insulin action, plasma lipid levels (9) , neuronal development and the immune system inter alia through modulation of eicosanoid (PG and leukotrine) synthesis, activation of orphan nuclear receptor and T-lymphocyte signalling (9,10) . They also regulate the transcription and activation of multiple genes (11 -13) . Hence, PUFA affect several metabolic pathways, and thus may have an impac...

Obesity polymorphisms identified in genome-wide association studies interact with n-3 polyunsaturated fatty acid intake and modify the genetic association with adiposity phenotypes in Yup’ik people

“…Animal models have shown significant reductions in fat mass when dietary n-3 PUFAs, namely eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), are substituted for saturated fats (Hainault et al 1993), monosaturated fats (Su and Jones 1993), and n-6 polyunsaturated fats (Jones 1989), after controlling for caloric intake. These findings have largely been confirmed by human studies (Thorsdottir et al 2007); however, information regarding whether the anti-obesity effects attributed to n-3 PUFA is dependent upon a specific genotype remains limited (Jourdan et al 2011). Knowledge about the interplay between genetic factors and consumption of n-3 PUFA in isolated populations with widely varying n-3 PUFA intake may facilitate the choice of more effective and specific measures of obesity prevention based upon individualized genetic makeup.…”

Relationship of the Reported Intakes of Fat and Fatty Acids to Body Weight in US Adults

“…Polymorphisms of varying frequencies and ethnic variability in numerous genes encoding proteins involved in various aspects of fatty acid metabolism are linked to the development of obesity [43,44]. These proteins include, but are not limited to fatty acid binding proteins (FABP), fatty acid amide hydrolase (FAAH), delta 6 desaturase (FADS2), the fatty acid transporter CD36, and peroxisomal proliferator activated receptor (PPAR) gamma [45,46,47,48,49]. The extent to which these polymorphisms modify energetic or satiety related responses of specific fatty acids requires further investigation.…”

The examination of fatty acid taste with edible strips

“…In addition, fatty acids modify the structure and function of plasma membrane lipid rafts, whose composition may be altered by the intake of dietary fats [2]. Elevated levels of serum fatty acids have been associated with an increased risk for insulin resistance and type 2 diabetes, cardiovascular disease, and abdominal obesity [3–5]. However, a high-fat (ketogenic) diet has been used as a nonpharmacologic therapy for some forms of epilepsy [6–7].…”