Prenatal Iron Deficiency Causes Long‐Term Alterations in Brown Adipose Tissue Quantity and Thermogenic Capacity in Adult Rats

Introduction Fetal exposure to an adverse intrauterine environment can lead to altered growth and developmental trajectories, thereby increasing susceptibility to chronic disease in later life. Iron deficiency (ID) is the most common nutritional disorder in the world, and pregnant women are the most susceptible subgroup. We have shown that prenatal ID programs offspring metabolic function, characterized by an increased propensity for fat accumulation in later life; however, the mechanisms underlying this metabolic function are unknown. Brown adipose tissue (BAT) is highly metabolically active tissue which generates large quantities of heat to maintain core body temperature. The capacity of BAT to burn calories as heat makes it an attractive therapeutic target for obesity. We sought to determine whether prenatal ID predisposes offspring to obesity by chronically altering the thermogenic capacity of BAT, and thus whole body metabolism. Methods Female Sprague Dawley rats were fed either a control or an iron‐restricted (3–10 ppm iron) diet prior to and throughout gestation. At birth, dams were fed a normal rat chow, and pups were subsequently fed a high‐fat/high‐sucrose diet at weaning (postnatal day 21). At 4wk of age, one male and female offspring from each litter were subjected to a chronic cold exposure protocol (4°C, 12h/day, 5wk) to stimulate brown fat, and one male and female littermate were maintained at room temperature (22°C). Metabolic parameters were analyzed in vivo via open‐circuit indirect calorimetry. Maximal thermogenic capacity from BAT was assessed following pharmacological stimulation with the β3 agonist CL316,243. Results Prenatal ID caused lower body weights in offspring from birth until 4wk of age, but both male and female offspring exhibited catch‐up growth when fed the high‐fat/high‐sucrose diet. Cold exposure increased BAT mass in all offspring (P<0.001), and this correlated with increased thermogenic capacity in all offspring (P<0.001). Whereas cold exposure had minimal effects on control offspring body weight and body composition, cold exposure prevented body weight and fat mass gain in male PID offspring (P<0.001), but not in female PID offspring. Conclusions Prenatal ID causes sex‐specific programming of body composition and BAT function in the offspring. BAT may therefore represent an attractive target for therapeutic intervention to prevent the obesity and metabolic function caused by early stressors such as prenatal ID. Support or Funding Information This research has been facilitated by the Women and Children's Health Research Institute through the generosity of the Stollery Children's Hospital Foundation and supporters of the Lois Hole Hospital for Women, and the Canadian Institutes of Health Research.

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