Obesity and obesogenic growth are both highly heritable and modified by diet in a nonhuman primate model the African green monkey (Chlorocebus aethiops sabaeus)

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity. STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a longitudinal clustering algorithm to detect obesogenic growth, and logistic growth curves implemented in nonlinear mixed effects models to estimate three growth parameters. We used maximum likelihood variance decomposition methods to estimate the genetic contributions to obesity-related traits and growth parameters, including a test for the effects of a calorie-restricted dietary intervention. We used multipoint linkage analysis to map implicated genomic regions. RESULTS: All measurements were significantly influenced by sex, and with the exception of WC, also influenced by maternal and post-natal diet. Chronic obesity outcomes were significantly associated with a pattern of extended growth duration with slow growth rates for BW. After accounting for environmental influences, all measurements were found to have a significant genetic component to variability. Linkage analysis revealed several regions suggested to be linked to obesity-related traits that are also implicated in human obesity and metabolic disorders. CONCLUSIONS: As in humans, growth patterns in vervets have a significant impact on adult obesity and are largely under genetic control with some evidence for maternal and dietary programming. These results largely mirror findings from human research, but reflect shorter developmental periods, suggesting that the vervet offers a strong genetic model for elucidating the ontogeny of human obesity.We thank the staff of the Vervet Research Colony at both UCLA and the Wake Forest School of Medicine for their assistance in vervet anesthetization and measurement and Margaret Chu for logistic support. Kylie Kavanagh, Lynn Fairbanks, Katie Hinde, and two anonymous reviewers provided invaluable feedback on earlier versions of this manuscript that improved it greatly. This research benefitted from funding provided by the National Institutes of Health: RR019963/OD010965 (MJJ, JRK, NBF and AJJ), RR016300/OD010980 (NBF, AJJ and CAS), 2T32NS048004-06A1 (CAS). (RR019963/OD010965 - National Institutes of Health; RR016300/OD010980 - National Institutes of Health; 2T32NS048004-06A1 - National Institutes of Health)Published versio