Long-term metabolic effects of malnutrition: Liver steatosis and insulin resistance following early-life protein restriction

Introduction: Malnutrition remains prevalent worldwide, and about 45% of all child deaths are linked to malnutrition. It is unclear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when exposed later in life to an obesogenic diet. The lack of understanding around this dietary "double burden" warrants studies to understand the long-term consequences postnatal malnutrition. We hypothesized that an early-life nutritional insult of low protein consumption in mice would lead to long-term metabolic disturbances that would exacerbate the development of obesogenic diet-induced fatty liver disease and insulin resistance. Methods: We investigated the effects of feeding a low protein diet (4% wt/wt) immediately after weaning for four weeks and subsequent feeding of a high carbohydrate high fat feeding for 16 weeks on metabolic function and development of non-alcoholic fatty liver disease (NAFLD). Results: Mice exposed to early-life protein restriction as a model for malnutrition demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate obesogenic diet-induced insulin resistance. In additional NAFLD scores were similar in low protein diet fed animals compared to regular protein fed animals after high carbohydrate high fat feeding. Conclusions: These data suggest that transient protein restriction in early-life does not exacerbate high carbohydrate high fat diet-induced NAFLD and insulin resistance in mice. (author)