Elucidation of thrifty features in adult rats exposed to protein restriction during gestation and lactation

Since the introduction of the thrifty phenotype hypothesis, the potential traits of thrift have been described in increasingly broad terms but biochemical and behavioral evidence of thrift has not been well demonstrated. The objective of our studies was to use a rodent model to identify features of thrift programmed by early life protein restriction. Robust programming of thrifty features requires a thrifty nutritional environment during the entire window of developmental plasticity. Therefore, pregnant rats were exposed to a low protein diet throughout the window of developmental plasticity spanning the period of gestation and lactation and its effects on energy acquisition, storage and expenditure in the adult offspring were examined. Maternal protein restriction reduced birth weight and produced long term reductions in body and organ weights in the offspring. Low protein offspring demonstrated an increased drive to seek food as evidenced by hyperphagia that was mediated by changes in plasma leptin and ghrelin levels. Hyperphagia was accompanied by increased efficiency in converting caloric intake into body mass. The higher feed efficiency was mediated by greater insulin sensitivity. Energy expenditure of low protein offspring in locomotion was not affected either in the light or dark phase. However, low protein offspring exhibited higher resting and basal metabolic rates as evidenced by higher core body temperature in the fed and fasted states. The increased thermogenesis was not mediated by thyroid hormones but by an increased sympathetic nervous system drive as reflected by a lower areal bone mineral density and bone mineral content and lower plasma adiponectin and triglyceride levels. Elevated thermogenesis in the low protein offspring possibly offsets the effects of hyperphagia, minimizes their chances of weight gain, and improves survivability. This constellation of metabolic features in the low protein offspring will maximize survival potential in a post natal environment of nutritional scarcity and constitute a thrifty phenotype.

► Perinatal protein restriction induced a variety of thrifty features in the offspring. ► Offspring exhibited chronic reduction in body weight and cumulative calorie intake. ► Offspring displayed hyperphagia attributed to changes in plasma leptin and ghrelin. ► The higher insulin sensitivity in the offspring enhanced post-weaning feed efficiency. ► Offspring increased thermogenesis by mounting a higher sympathetic drive.