Post-nursing early life macronutrient balance promotes persistent and malleable biometric and metabolic traits in mice.

It is known that dietary factors within the gestational and nursing period affect early life and stably affect later life traits in animals. However, there is very little understanding of whether dietary factors within the early life period from post-nursing to adulthood affect traits in adulthood. To address this, we conducted studies on male C57Bl/6J mice fed from 3 weeks (immediately post-nursing) until 12 weeks (full maturity) using nine different diets varying in all three major macronutrients to parse out the effects of individual macronutrients. Early life macronutrient balance affected body composition and glucose homeostasis in early adulthood, with dietary protein and fat showing major effects. Despite this, mice showed rapid reversal of the effects on body composition and glucose homeostasis of early life diet feeding, upon standard diet feeding in adulthood. However, some traits were persistent, with early life low dietary protein levels stably affecting lean and muscle mass, and early life dietary fat levels stably affecting serum and liver triglyceride levels. In summary, macronutrient balance in the post-nursing early life period does not stably affect adiposity or glucose homeostasis but does impact muscle mass and lipid homeostasis in adulthood, with prominent effects of both protein and fat levels. KEY POINTS: Early life dietary low protein and high fat levels lowered and heightened body mass, respectively. These effects did not substantially persist into adulthood with rapid catch-up growth on a normal diet. Early life protein (negative) and fat (positive) levels affected fat mass. Early life low protein levels negatively affected lean mass. Low protein effects on lower lean and muscle mass persisted into adulthood. Early life macronutrient balance effects did not affect later life glucose homeostasis but early life high fat level affected later life dyslipidaemia. Effects of dietary carbohydrate levels in early and later life were minor.