Genetic and Environmental Influences on Adiponectin, Leptin, and BMI Among Adolescents in Taiwan: A Multivariate Twin/Sibling Analysis

Abstract Circulating levels of leptin and adiponectin are closely associated with obesity. However, it is not known whether there are common shared genes or environment exerting influences on the levels of leptin, adiponectin, and BMI. We aimed to assess the relative contribution of genes and environment to adiponectin, leptin, and BMI individually as well as simultaneously to the three measures. Our subjects included a total of 228 twin/sibling pairs aged 12 to 18 (130 monozygotic twins, 68 dizygotic twins and 30 sibling pairs) were recruited from the middle schools. Multivariate analyses were applied to twin/sibling data using structural equation modeling. The results showed that intraclass correlations for adiponectin, leptin and BMI were higher in the MZ twins than those in the DZ/SP group. The relative contribution of genes to adiponectin (39%) was comparable to those of shared environment (40%). In contrast, leptin and BMI were influenced mostly by genes (74% and 89%, respectively). The multivariate genetic analyses showed that a latent factor underlying the three measures was identified, with BMI being equivalent to this latent factor. The BMI-dependent genetic factor explains only 15% and 34% of variation of adiponectin and leptin, respectively. These data indicate a differential contribution of genetic factors for the variation of adiponectin, leptin and BMI. More importantly, only a small portion of the genetic influences on adiponectin and leptin was attributed to BMI. Our findings provided more insight into the complex regulation of adiponectin and leptin in obesity.

[1]  K. Clément,et al.  A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10 , 1998, Nature Genetics.

[2]  J. Kaprio,et al.  Genetic and environmental factors in relative weight from birth to age 18: The Swedish Young Male Twins Study , 2007, International Journal of Obesity.

[3]  V. Somers,et al.  Heritability of plasma leptin levels: a twin study. , 1999, Journal of hypertension.

[4]  J. Kaprio,et al.  Heritability of leptin levels and the shared genetic effects on body mass index and leptin in adult Finnish twins , 2001, International Journal of Obesity.

[5]  S. Cole,et al.  Linkage analysis of circulating levels of adiponectin in hispanic children , 2007, International Journal of Obesity.

[6]  L. Groop,et al.  Relationships of plasma adiponectin level and adiponectin receptors 1 and 2 gene expression to insulin sensitivity and glucose and fat metabolism in monozygotic and dizygotic twins. , 2007, The Journal of clinical endocrinology and metabolism.

[7]  L. Chuang,et al.  Human genetics of adiponectin in the metabolic syndrome , 2006, Journal of Molecular Medicine.

[8]  J. Troendle,et al.  Influence of serum leptin on weight and body fat growth in children at high risk for adult obesity. , 2007, The Journal of clinical endocrinology and metabolism.

[9]  L. Baur,et al.  Body mass index and waist circumference in midchildhood and adverse cardiovascular disease risk clustering in adolescence. , 2007, The American journal of clinical nutrition.

[10]  D. Smelser,et al.  Genome-wide scan for adiposity-related phenotypes in adults from American Samoa , 2007, International Journal of Obesity.

[11]  K. Lange,et al.  Extensions to pedigree analysis III. Variance components by the scoring method , 1976, Annals of human genetics.

[12]  A. Adeyemo,et al.  A Genome‐wide Scan of Loci Linked to Serum Adiponectin in Two Populations of African Descent , 2007, Obesity.

[13]  A. Doria,et al.  Genetic Influences of Adiponectin on Insulin Resistance, Type 2 Diabetes, and Cardiovascular Disease , 2007, Diabetes.

[14]  T. Spector,et al.  Lack of heritability of circulating leptin concentration in humans after adjustment for body size and adiposity using a physiological approach , 2001, International Journal of Obesity.

[15]  Y. Hung,et al.  Correlation of plasma leptin and adiponectin with insulin sensitivity and β‐cell function in children – the Taipei Children Heart Study , 2006, International journal of clinical practice.

[16]  J. O’Connell,et al.  Linkage of plasma adiponectin levels to 3q27 explained by association with variation in the APM1 gene. , 2005, Diabetes.

[17]  Claude Bouchard,et al.  The Human Obesity Gene Map: The 2005 Update , 2006, Obesity.

[18]  L. Chuang,et al.  The Taipei Adolescent Twin/Sibling Family Study II: Depression, Insulin Resistance, and Hormonal Factors , 2006, Twin Research and Human Genetics.

[19]  T. Tai,et al.  Sex-related differences between adiponectin and insulin resistance in schoolchildren. , 2004, Diabetes care.

[20]  Chueh Chang,et al.  Diagnosis of Zygosity by Questionnaire and Polymarker Polymerase Chain Reaction in Young Twins , 1999, Behavior genetics.

[21]  S. Hunt,et al.  Relationship of ghrelin and leptin hormones with body mass index and waist circumference in a random sample of adults. , 2006, Journal of the American Dietetic Association.

[22]  H. Akaike.  Factor analysis and AIC , 1987 .

[23]  W. Sheu,et al.  Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of Chinese and Japanese origin. , 2004, The Journal of clinical endocrinology and metabolism.

[24]  C. Ji,et al.  A twin study for serum leptin, soluble leptin receptor, and free insulin-like growth factor-I in pubertal females. , 2005, The Journal of clinical endocrinology and metabolism.

[25]  G. Imperatore,et al.  Childhood obesity: is it time for action? , 2006, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[26]  G. Steinberg,et al.  Adipose tissue as an endocrine organ , 2010, Molecular and Cellular Endocrinology.

[27]  L. Kuller,et al.  Genetic determination of adiponectin and its relationship with body fat topography in multigenerational families of African heritage. , 2007, Metabolism: clinical and experimental.

[28]  J. Stockman.  Fast-food Habits, Weight Gain, and Insulin Resistance (the CARDIA Study): 15-Year Prospective Analysis , 2006 .

[29]  Bruce M. Spiegelman,et al.  Adipocytes as regulators of energy balance and glucose homeostasis , 2006, Nature.

[30]  T. Funahashi,et al.  Genome-wide linkage analysis of serum adiponectin in the Pima Indian population. , 2003, Diabetes.

[31]  S. Cole,et al.  Genetic and environmental factors influencing fasting serum adiponectin in Hispanic children. , 2005, The Journal of clinical endocrinology and metabolism.

[32]  M. Drent,et al.  The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[33]  N. Martin,et al.  The validity of twin studies , 2000 .

[34]  A. Thapar,et al.  Methodology for Genetic Studies of Twins and Families , 1993 .

[35]  Nader Rifai,et al.  Association between dietary factors and plasma adiponectin concentrations in men. , 2005, The American journal of clinical nutrition.

[36]  J. Blangero,et al.  The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. , 2001, The Journal of clinical endocrinology and metabolism.

[37]  T. Sørensen,et al.  [Childhood body mass index and the risk of coronary heart disease in adulthood]. , 2007, Ugeskrift for laeger.

[38]  N. Krebs,et al.  Assessment of Child and Adolescent Overweight and Obesity , 2007, Pediatrics.

[39]  J. Connell,et al.  Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins , 2004, Clinical endocrinology.

[40]  Christopher J. Williams,et al.  Heritability of plasma adiponectin levels and body mass index in twins. , 2007, The Journal of clinical endocrinology and metabolism.

[41]  Ho-Young Son,et al.  Epidemic obesity and type 2 diabetes in Asia , 2006, The Lancet.

[42]  J. Shim,et al.  Association between hypoadiponectinemia and cardiovascular risk factors in nonobese healthy adults. , 2006, Metabolism: clinical and experimental.

[43]  R. Bayoumi,et al.  Heritability of Determinants of the Metabolic Syndrome among Healthy Arabs of the Oman Family Study , 2007, Obesity.