# The interplay of genetics and fatty acid metabolism: exploring their impact on metabolic syndrome in Swedish men

## TL;DR

This study explores how genetic variants and fatty acid metabolism in Swedish men influence the risk of metabolic syndrome over 20 years.

## Contribution

The study identifies specific SNPs and metabolic parameters that predict metabolic syndrome risk in men two decades later.

## Key findings

- Genetic variants in BDNF, FTO, and ETV5 genes are linked to metabolic syndrome risk in older age.
- Low D5D activity and HDL cholesterol levels at age 50 predict MetS risk at age 70.
- Abdominal skinfold thickness and fasting glucose also contribute to long-term MetS risk.

## Abstract

Genetic risk variants for obesity and metabolic syndrome (MetS) have been identified, but their link to relevant metabolic health parameters warrants further attention. This study aimed to investigate the extent to which single-nucleotide polymorphisms (SNPs) associated with obesity are linked to changes in fatty acid (FA) profiles in serum cholesteryl esters, lipid metabolism, and MetS risk.

Data from the Uppsala Longitudinal Study of Adult Men (ULSAM), conducted in men at age 50 (N = 1973) and age 70 (N = 982), were used to investigate SNPs associated with body mass index (BMI) in genome-wide association studies with metabolic parameters at age 50. The significant SNPs and associated lipid parameters were then used as predictors of MetS over a 20-year follow-up period, at age 70 in binary regression models.

The two genes, the brain-derived neurotrophic factor gene (BDNF) (rs7103411) and the fat mass and obesity-associated gene (FTO) (rs1558902), together with delta-5-desaturase (D5D) activity, 20:5n-3 in serum cholesteryl esters (CE), fasting blood glucose, abdominal skinfold thickness, apolipoprotein-B, and high-density lipoprotein cholesterol (HDL-C) at age 50, significantly predicted the risk of MetS at age 70.

The findings suggest a considerable contribution of the SNPs BDNF rs7103411, FTO rs1558902, and ETV5 rs9816226, along with low D5D activities and serum levels of HDL-C in men at age 50, to the risk for MetS 20 years later.

The online version contains supplementary material available at 10.1186/s12937-025-01168-8.