Prevention of obesity in Infants of overweight and obese women

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Throughout the world, obesity and metabolic syndrome are an ongoing epidemic crisis, presenting major public health challenges and significant economic burdens. The developmental programming effects of the in-utero environment is demonstrated by the increased risk of large for gestational age (LGA) newborns and childhood and adult obesity in offspring of overweight/obese (OW/OB) mothers. Animal studies have confirmed that maternal obesity and high fat diet programs the offspring appetite center, the arcuate nucleus, resulting in offspring hyperphagia and rapid weight gain, contributing to the generational cycle of obesity. Compounding the effect of programmed hyperphagia is the impact of breast milk caloric content. Despite evidence that breastfeeding reduces the incidence of childhood obesity, breastfeed LGA infants’ childhood obesity rates are nearly 50% greater than formula fed appropriate for gestational age infants. Maternal BMI and dietary intake are highly correlated with milk total calorie and fat content. Our laboratory studies show that offspring born to and nursed by obese rat dams exhibit hyperphagia and develop early life and adult obesity. In contrast, if these offspring are cross fostered and nursed by non-obese dams (matched for gender and litter-size), the offspring grow to normal weight and BMI as adults. These studies suggest that despite programmed offspring hyperphagia at birth, the restriction to control dam milk prevents excessive newborn weight gain and obesity. We propose that normalized caloric intake and newborn growth will prevent the onset of infant obesity, hyperleptinemia (and leptin resistance), and thus normalize appetite throughout childhood. The proposed studies will 1) Confirm that OW/OB mothers’ milk has increased total calorie content and that infants of OW/OB mothers have increased milk intake, and as an intervention 2) Determine if titrated human milk or formula calorie intake prevents excessive infant weight gain in the first six months of life. This highly innovative study will examine the potential efficacy of a novel preventative strategy to prevent the development of infant obesity and interrupt the generational cycle of obesity.