Abstract
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.
Highlights
Despite all global efforts, malnutrition is still a major burden in developing countries and is considered the most relevant risk factor for illness and death of millions of young children
We first characterized the impact on weight gain and stunting in C57BL/6 mice of a Low-Protein Diet (LPD) feeding followed by 4 weeks of recovery with regular chow diet and by HFHC diet feeding for 16 weeks (Fig 1A)
Measurements of average weekly food intake during each feeding period indicate that there was no significant difference in the weekly food intake among the LPD and normal (18%) protein diet (NPD)-fed mice during the first burden/malnutrition period, during the recovery period, the weekly food intake in the LPD-fed mice had significantly increased as compared with the NPD-fed mice (Fig 1E)
Summary
Malnutrition is still a major burden in developing countries and is considered the most relevant risk factor for illness and death of millions of young children. The increase in obesity and associated chronic metabolic disorders is a major public health problem in developed nations and in low-income and middle-income countries [1]. Extensive epidemiological studies have indicated that malnutrition during intrauterine and perinatal life has deleterious health effects that can last throughout the life of an individual [8,9,10]. This process, termed nutritional or developmental programming, allows specific physiological and metabolic adaptations that persist even after the early nutritional stress is resolved [11]. This programming is mediated by epigenetic alterations that change long-term gene expression and result in maintenance of the acquired phenotype [12,13,14]
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