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PLoS One. 2018 Jul 2;13(7):e0199916. doi: 10.1371/journal.pone.0199916. eCollection 2018.

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

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Translational Medicine Research Program, The Hospital for Sick Children, Toronto, ON, Canada.
Morosky College of Health Professions and Sciences, Gannon University, Erie, PA, United States of America.
Department of Laboratory Medicine and Pathology, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, ON, Canada.
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.


Early postnatal-life malnutrition remains prevalent globally, and about 45% of all child deaths are linked to malnutrition. It is not clear whether survivors of childhood malnutrition suffer from long-term metabolic effects, especially when they are later in life exposed to a fat and carbohydrate rich obesogenic diet. The lack of knowledge around this dietary "double burden" warrants studies to understand the long-term consequences of children previously exposed to 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 diet-induced insulin resistance and non-alcoholic fatty liver disease (NAFLD). 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 NAFLD. Mice exposed to early-life protein restriction demonstrated a transient glucose intolerance upon recovery by regular chow diet feeding. However, protein restriction after weaning in mice did not exacerbate an obesogenic diet-induced insulin resistance or progression to NAFLD. These data suggest that transient protein restriction in early-life does not exacerbate an obesogenic diet-induced NAFLD and insulin resistance.

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