Plasma leptin levels are related to body composition, sex, insulin levels and the A55V polymorphism of the UCP2 gene

• Published in: International Journal of Obesity Vol. 31; no. 8; pp. 1311 - 1318
• Main Authors: Rance, K.A, Johnstone, A.M, Murison, S, Duncan, J.S, Wood, S.G, Speakman, J.R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 01-08-2007; Nature Publishing Group
• Subjects: Adipocytes; Adipose tissue; Adult; adults; age; Biological and medical sciences; blood chemistry; blood plasma; Body composition; Body Composition - physiology; Body fat; Body mass index; Cross-Sectional Studies; Cross-sections; Diabetes; dual-energy X-ray absorptiometry; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; gender differences; genes; Genetic aspects; genetic polymorphism; Genetic polymorphisms; genetic variation; genotype; hormone secretion; human genetics; Humans; Hypertension; Insulin; Insulin - blood; Insulin resistance; Ion Channels - genetics; Ion Channels - metabolism; Leptin; Leptin - blood; Male; Medical sciences; men; Metabolic diseases; Metabolism; Middle Aged; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; molecular sequence data; Obesity; Physiological aspects; physiological regulation; Polymorphism; Polymorphism, Single Nucleotide - genetics; promoter regions; Promoter Regions, Genetic - genetics; Sex Characteristics; Thyroxine - blood; Triiodothyronine - blood; Uncoupling Protein 2; Vertebrates: anatomy and physiology, studies on body, several organs or systems; White people; Whites; women; Scotland; United Kingdom > UK; Human; Biological fluid; Obesity; Pancreatic hormone; Genetic variability; Nutrition; Nutrition disorder; Sex; Genotype; Metabolic diseases; Adipokine; Insulin; Body composition; Blood plasma; UCP2 polymorphism; Gene; Leptin; Genetics; Nutritional status; Polymorphism
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/sj.ijo.0803535

Objective: Circulating leptin levels show a high degree of individual variability even after the main effect of body fatness is accounted for. We therefore wanted to determine the roles of variation in body composition, age, sex and polymorphisms of the UCP2 gene and promoter region on levels of circulating leptin. Subjects: One hundred and fifty Caucasian subjects, which represented a cross-section of the population from NE, Scotland, were recruited. Measurements: Body composition was measured using dual X-ray absorptiometry. Fasted circulating leptin, insulin, T3 and T4 levels were measured, and all individuals were genotyped for the UCP2 polymorphisms A55V, -866G>A and exon-8 ins/del. Results: The results indicate that circulating leptin was significantly related to sex and principle component (PC) scores representing overall adipose tissue mass and a second representing the contrast of central to peripheral bone mineral content. Residual leptin was associated with the A55V polymorphism (P< 0.001) explaining 11.3% of the residual variance. There was a marginal effect associated with exon-8 ins/del (P = 0.045) explaining 4.4% of the residual variance in leptin. Log(e) transformed circulating fasting insulin was related to PC scores representing general adiposity and sex. Residual Log(e) insulin was associated with the A55V and exon-8 ins/del polymorphisms explaining 5.7% (P=0.015) and 5% (P = 0.026) of the residual variation, respectively. The -866G>A polymorphism was not significantly associated with residual leptin or insulin. Leptin and insulin were significantly (P = 0.007) correlated. Statistically removing the effect of insulin on leptin still showed association between leptin and A55V (P = 0.002). Removing the effect of leptin on insulin, the A55V polymorphism was no longer significant (P=0.120). After accounting for the correlation between insulin and leptin, the exon-8 ins/del was no longer significant for residual leptin (P = 0.119) or Log(e) insulin (P = 0.252). Conclusion: These data suggest that the A55V polymorphism directly affected the levels of leptin but not via an effect on insulin.