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

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.

SUBMITTER: Dalvi PS

PROVIDER: S-EPMC6028108 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Dalvi Prasad S PS Yang Steven S Swain Nathan N Kim Junsoo J Saha Senjuti S Bourdon Celine C Zhang Ling L Chami Rose R Bandsma Robert H J RHJ

PloS one 20180702 7

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 ...[more]

PMID: 29965973

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Project description:BackgroundSevere acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences.MethodsWe extracted genomic DNA from muscle biopsies obtained from adult survivors of kwashiorkor (n=21) or marasmus (n=23) and compared epigenetic profiles (CpG methylation) between the two groups using the Infinium® 450K BeadChip array.FindingsWe found significant differences in methylation of CpG sites from 63 genes in skeletal muscle DNA. Gene ontology studies showed significant differential methylation of genes in immune, body composition, metabolic, musculoskeletal growth, neuronal function and cardiovascular pathways, pathways compatible with the differences in the pathophysiology of adult survivors of SAM.InterpretationThese findings suggest persistent developmental influences on adult physiology in survivors of SAM. Since children who develop marasmus have lower birth weights and after rehabilitation have different intermediary metabolism, these studies provide further support for persistent developmentally-induced phenomena mediated by epigenetic processes affecting both the infant response to acute malnutrition and later life consequences.FundingSupported by a Grant from the Bill and Melinda Gates Foundation (Global Health OPP1066846), Grand Challenge "Discover New Ways to Achieve Healthy Growth."Evidence before this studyPrevious research has shown that infants who develop either kwashiorkor or marasmus in response to SAM differ in birth weight and subsequently have different metabolic patterns in both infancy and adulthood.Added value of this studyThis study demonstrates epigenetic differences in the skeletal muscle of adult survivors of marasmus versus kwashiorkor and these differences are in genes that may underlie the longer-term consequences.Implications of all the available evidenceThese data are compatible with the different clinical responses to SAM arising from developmentally-induced epigenetic changes laid down largely before birth and provide evidence for the predictive adaptive response model operating in human development.

Dataset Information

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

Publications

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

Similar Datasets

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