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 F2α (PGF2α) were examined. Results: Single-nucleotide polymorphisms 10076C>G/10171A>T showed the strongest positive linkage disequilibrium (LD) (D′ = 0.923, R2 = 0.839, P<0.001) and SNPs11482G>A/14995A>T showed moderate positive LD (D′ = 0.824, R2 = 0.578, P<0.001). Calorie restriction induced 4.6% weight loss with significant abdominal fat reduction. In response to weight loss, subjects with nCA/nCA haplotypes at SNPs 10076C>G/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 F2α 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 PGF 2α 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 PGF2α and oxidized LDL.
Bibliographical noteFunding Information:
We sincerely thank research subjects who participated in the studies described in this report. We also thank the support of National Research Laboratory project #2005-01572, Ministry of Science & Technology, Korea Science & Engineering Foundation (R01-2003-0000-11709-0), Korea Health 21 R&D Projects, Ministry of Health & Welfare (00-PJ3-PG6-GN-01-0001) and NIH/NHLBI # HL54776, and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service on this study. Financial support: (1) National Research Laboratory project #2005-01572, Ministry of Science & Technology, Korea (2) Korea Science & Engineering Foundation (R01-2003-0000-11709-0) (3) Korea Health 21 R&D Projects, Ministry of Health & Welfare (00-PJ3-PG6-GN-01-0001) (4) NIH/NHLBI # HL54776, and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Endocrinology, Diabetes and Metabolism
- Nutrition and Dietetics