Fetal growth restriction promotes physical inactivity and obesity in female mice

摘要: Environmental exposures during critical periods of prenatal and early postnatal life affect the development mammalian body weight regulatory mechanisms, influencing lifelong risk obesity. The specific biological processes that mediate persistence such effects, however, remain poorly understood. objectives this study were to determine developmental timing physiological basis obesity-promoting effect previously reported in offspring obese agouti viable yellow (Avy/a) mothers. Newborn Avy/a lean (a/a) mothers cross-fostered shortly after birth separately effects utero or suckling period exposure dams. Body composition, food intake, physical activity energy expenditure measured weaning adulthood. Offspring dams paradoxically experienced fetal growth restriction, which was followed by adult-onset obesity specifically females. Our main analyses focused on wild-type offspring, because a subset adult contracted kidney disease resembling diabetic nephropathy. Detailed characterization demonstrated that, both adulthood, female mice born are not hyperphagic but have reduced expenditure. No coordinated changes detected male offspring. Mediational regression analysis our longitudinal data supported causal pathway restriction persistently reduces activity, leading consistent with several recent human epidemiological studies showing female-specific perinatal nutritional later obesity, provide novel mechanistic insight may occur via permanent sex-specific one’s inherent propensity for activity.