Genetic variation at the perilipin locus is associated with changes in serum free fatty acids and abdominal fat following mild weight loss

Objective: Perilipin (PLIN) is a class of protein-coating lipid droplets in adipocytes. We aimed to examine the association between common single-nucleotide polymorphisms (SNPs) at PLIN locus with circulating free fatty acid (FFA) and abdominal fat distribution in response to weight loss. Methods: Non-diabetic/overweight-obese Koreans (n=177) participated in a 12-week calorie restriction (-300kcal/day) program. Seven SNPs (6209T>C, 10076C>G, 10171A>T, 11482G>A, 13042A>G, 13048C>T and 14995A>T), abdominal fat areas (visceral/subcutaneous fat areas at 1st lumbar and 4th lumbar levels), serum lipids, glucose, insulin, FFA, oxidized low-density lipoprotein (LDL) and urinary 8-epi-prostaglandin F2 (PGF2) were examined. Results: Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D'=0.923, R 2=0.839, PA/14995A>T showed moderate positive LD (D'=0.824, R 2=0.578, PG/10171A>T showed greater reduction in FFA levels than those with CA/CA haplotype (CA/CA: C/C at SNP 10076 and A/A at SNP 10171, nCA: non-CA haplotype carrier). On the other hand, subjects with nGA/nGA haplotype at SNPs 11482G>A/14995A>T had increased FFA levels with a rapid loss in abdominal fat, whereas GA/GA haplotype carriers had reduction in FFA levels. These results still remained significant after adjusting for age, gender and BMI. Prostaglandin F2alpha and oxidized LDL were also more reduced in GA/GA haplotype carriers than in nGA haplotype carriers. This effect remained significant after adjusting for baseline level, age, gender and BMI. Paradoxically, nGA haplotype carriers had increased levels of urinary PGF2alpha after weight reduction. Conclusion: Fasting plasma FFA changes following a modest weight loss in overweight-obese subjects are influenced by the genetic variability at the PLIN locus. Furthermore, circulating FFA changes rather than body fat itself may determine changes in lipid peroxides such as urinary PGF2alpha and oxidized LDL.