Objective: Prevention would be the ideal public health strategy to face the current obesity epidemic. Adoption of healthy lifestyles during the first years of college or university could prevent the onset of weight gain associated with this period of acquired independence and eventually decrease the incidence of obesity. Design: Randomized-controlled trial over a period of 2 years. The subjects received an educational/behavioral intervention (small group seminars) designed to help maintain a healthy lifestyle or no specific intervention (control group). Subjects: One-hundred and fifteen non-obese freshmen in a Faculty of Medicine. Measurements: Anthropometric measurements, physical activity level, fitness level, food intake and lipid profile were recorded at predetermined intervals. Results: The control group gained weight, whereas the intervention group lost a slight amount of weight over 2 years. The difference between the two groups was 1.3 kg at the end of the follow-up, the trend of weight gain differing between the two groups during the 2-year intervention period (P ¼ 0.04). There was no detectable difference in fitness, physical activity level or total caloric intake between the two groups during follow-up. However, plasma triglyceride levels increased in the control group and decreased in the intervention group (P ¼ 0.04). Conclusion: In this randomized-controlled trial, a small-group seminar educational/behavioral intervention successfully prevents weight gain in normal weight young healthy university students. Such small absolute changes in body composition and lipid profile, if maintained over a prolonged period, could result in significant long-term health benefits for the general population (ClinicalTrial.gov registration number: NCT00306449).

Leptin is an adipokine that acts in the central nervous system and regulates energy balance. Animal models and human observational studies have suggested that leptin surge in the perinatal period has a critical role in programming long-term risk of obesity. In utero exposure to maternal hyperglycemia has been associated with increased risk of obesity later in life. Epigenetic mechanisms are suspected to be involved in fetal programming of long term metabolic diseases. We investigated whether DNA methylation levels near LEP locus mediate the relation between maternal glycemia and neonatal leptin levels using the 2-step epigenetic Mendelian randomization approach. We used data and samples from up to 485 mother-child dyads from Gen3G, a large prospective population-based cohort. First, we built a genetic risk score to capture maternal glycemia based on 10 known glycemic genetic variants (GRS 10 ) and showed it was an adequate instrumental variable (b D 0.046 mmol/L of maternal fasting glucose per additional risk allele; SE D 0.007; P D 7.8 £ 10 ¡11 ; N D 467). A higher GRS 10 was associated with lower methylation levels at cg12083122 located near LEP (b D ¡0.072 unit per additional risk allele; SE D 0.04; P D 0.05; N D 166). Direction and effect size of association between the instrumental variable GRS 10 and methylation at cg12083122 were consistent with the negative association we observed using measured maternal glycemia. Lower DNA methylation levels at cg12083122 were associated with higher cord blood leptin levels (b D ¡0.17 log of cord blood leptin per unit; SE D 0.07; P D 0.01; N D 170). Our study supports that maternal glycemia is part of causal pathways influencing offspring leptin epigenetic regulation.

Our findings showed higher maternal and cord leptin, and lower maternal adiponectin are associated with lower offspring adiposity from childhood to early adolescence, independent of maternal BMI and GWG. However, the strength of these associations was not constant over time.

Obesity has now reached epidemic proportions. Epidemiological studies in the past decades have shown that adults gain weight and adiposity from the early twenties until their sixties. In the paediatric population, growing numbers of children and adolescents put on unhealthy weight. Many environmental, socio-economical and biological determinants that predispose to weight gain have been identified thus far. The aim of the present review is to summarize the current knowledge on the role of the circulating levels of adipokines and other entero-insular hormones and biological markers of obesity to predict weight gain in humans. The review focuses on relationship between hormonal and biochemical markers (insulin, insulin-like growth factors, gastrointestinal hormones, leptin, adiponectin, resistin, inflammatory proteins and cytokines) and weight gain in prospective studies. The complex relationships displayed by these hormonal factors with future weight gain in humans are critically reviewed and integrative models are proposed. Overall, most of the studies reported to date made adjustments for baseline body mass index but failed to consider dietary intake and physical activity as confounding factors. Outstanding questions are raised and new directions for future prospective studies are proposed in order to improve our understanding of the role of biological determinants of energy balance and development of obesity in humans.