Abstract
Adipose tissue secreted cytokines (adipocytokines) have significant effects on the physiology and pathology of human metabolism relevant to diabetes and cardiovascular disease. We determined the relationship of the pattern of these circulating hormones with obesity-related phenotypes and whether such pattern is transmitted from parent to offspring. A combined total of 403 individuals from 156 consenting Saudi families divided into initial (119 families with 123 adults and 131 children) and replication (37 families with 58 adults and 91 children) cohorts were randomly selected from the RIYADH Cohort study. Anthropometrics were evaluated and metabolic measures such as fasting serum glucose, lipid profiles, insulin, leptin, adiponectin, resistin, tumor necrosis factor alpha (TNFα), activated plasminogen activator inhibitor 1 (aPAI1), high sensitivity C-reactive protein (hsCRP) and angiotensin II were also assessed. Parent-offspring regressions revealed that with the exception of hsCRP, all hormones measured showed evidence for significant inheritance. Principal component (PC) analysis of standardized hormone levels demonstrated surprising heritability of the three most common axes of variation. PC1, which explained 21% of the variation, was most strongly loaded on levels of leptin, TNFα, insulin, and aPAI1, and inversely with adiponectin. It was significantly associated with body mass index (BMI) and phenotypically stronger in children, and showed a heritability of ∼50%, after adjustment for age, gender and generational effects. We conclude that adipocytokines are highly heritable and their pattern of co-variation significantly influences BMI as early as the pre-teen years. Investigation at the genomic scale is required to determine the variants affecting the regulation of the hormones studied.
Highlights
The rising epidemic of overweight and obesity among developing nations has been well established in several epidemiological studies of different ethnic groups from all over the world [1,2,3]
It is important to stress that the indigenous Saudi population seems to have an increased genetic predisposition to develop diabetes mellitus type 2 (DM T2), which is further amplified by increased prevalence of obesity, high rates of consanguinity, and the presence of other components of the metabolic syndrome (MetS) [9]
After adjustment for gender and generational effects, body mass index (BMI) was significantly influenced by five hormones
Summary
The rising epidemic of overweight and obesity among developing nations has been well established in several epidemiological studies of different ethnic groups from all over the world [1,2,3]. In the Kingdom of Saudi Arabia (KSA), the most recent study conducted to determine the baseline national prevalence of childhood obesity indicated an over-all prevalence of 9.3%, considered intermediate between developing and industrialized nation [8]. It is important to stress that the indigenous Saudi population seems to have an increased genetic predisposition to develop diabetes mellitus type 2 (DM T2), which is further amplified by increased prevalence of obesity, high rates of consanguinity, and the presence of other components of the metabolic syndrome (MetS) [9]. The rapid industrializations in KSA and other developing nations have been accompanied by increased prevalence of MetS even among younger populations [10]
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