Variation in the FFAR1 gene modifies BMI, body composition and beta-cell function in overweight subjects: an...

Area of Science:

• Genetics and Genomics
• Metabolic Diseases
• Human Physiology

Background:

• The FFAR1 receptor, a G-protein coupled receptor for long-chain fatty acids, is widely expressed with high density in the pancreas and central nervous system.
• FFAR1 is implicated in insulin sensitivity, lipotoxicity, and type 2 diabetes.
• This study focuses on three common FFAR1 single nucleotide polymorphisms (SNPs): rs2301151, rs16970264, and rs1573611.

Purpose of the Study:

• To investigate the impact of three common FFAR1 SNPs on pancreatic function, body mass index (BMI), body composition, and plasma lipids.
• To determine if FFAR1 gene variations are associated with metabolic risk factors.
• To explore the relationship between FFAR1 SNPs and key metabolic parameters in an overweight cohort.

Main Methods:

• Utilized baseline data from the RISCK study, a cohort of overweight individuals at increased cardiometabolic risk.
• Employed detailed phenotyping to assess the effects of FFAR1 SNPs on various metabolic and anthropometric measures.
• Analyzed the combined and individual effects of rs2301151, rs16970264, and rs1573611 on BMI, body composition, plasma lipids, insulin sensitivity, and beta-cell function.

Main Results:

• FFAR1 gene region SNPs were associated with variations in body composition and plasma lipid profiles.
• Combined effects of the three SNPs showed a cumulative impact on BMI, body composition, and total cholesterol.
• SNP rs1573611 significantly influenced BMI and body fat percentage, while other SNPs affected total, LDL, and HDL cholesterol levels.
• No significant direct effects of the three SNPs on insulin sensitivity or beta-cell function were observed, though accumulated risk alleles showed reduced beta-cell function with increased plasma fatty acids (>C6).

Conclusions:

• Common FFAR1 gene SNPs are linked to differences in body composition and plasma lipids.
• These observed metabolic alterations associated with FFAR1 SNPs do not appear to be mediated by direct changes in insulin sensitivity or beta-cell function.
• The study highlights the role of FFAR1 genetic variations in modulating adiposity and lipid metabolism independently of direct effects on pancreatic islet function.