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Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition.

ABSTRACT: Maternal overnutrition has been associated with increased susceptibility to develop obesity and neurological disorders later in life. Most epidemiological as well as experimental studies have focused on the metabolic consequences across generations following an early developmental nutritional insult. Recently, it has been shown that maternal high-fat diet (HFD) affects third-generation female body mass via the paternal lineage. We showed here that the offspring born to HFD ancestors displayed addictive-like behaviors as well as obesity and insulin resistance up to the third generation in the absence of any further exposure to HFD. These findings, implicate that the male germ line is a major player in transferring phenotypic traits. These behavioral and physiological alterations were paralleled by reduced striatal dopamine levels and increased dopamine 2 receptor density. Interestingly, by the third generation a clear gender segregation emerged, where females showed addictive-like behaviors while male HFD offspring showed an obesogenic phenotype. However, methylome profiling of F1 and F2 sperm revealed no significant difference between the offspring groups, suggesting that the sperm methylome might not be the major carrier for the transmission of the phenotypes observed in our mouse model. Together, our study for the first time demonstrates that maternal HFD insult causes sustained alterations of the mesolimbic dopaminergic system suggestive of a predisposition to develop obesity and addictive-like behaviors across multiple generations.

SUBMITTER: Sarker G

PROVIDER: S-EPMC6185972 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition.

Sarker Gitalee G Berrens Rebecca R von Arx Judith J Pelczar Pawel P Reik Wolf W Wolfrum Christian C Peleg-Raibstein Daria D

Translational psychiatry 20181012 1

Maternal overnutrition has been associated with increased susceptibility to develop obesity and neurological disorders later in life. Most epidemiological as well as experimental studies have focused on the metabolic consequences across generations following an early developmental nutritional insult. Recently, it has been shown that maternal high-fat diet (HFD) affects third-generation female body mass via the paternal lineage. We showed here that the offspring born to HFD ancestors displayed ad ...[more]

PMID: 30315171

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Project description:Background and objectivesStudies in low-and middle-income countries where nutrition transition is underway provides mixed evidence of double burden of maternal overnutrition and child undernutrition among mother-child pairs. Shifting dietary pattern and rapid increase in overweight/obesity among adults with persistent child undernutrition indicate that India is experiencing nutrition transition and double burden of malnutrition. Hence, the study explores the presence of and the factors associated with mother-child dyads of over- and undernutrition in India.Methods and materialsThe study uses National Family Health Survey 2015-16 data. The analytic sample consists of 28,817 weighted mother-child pairs where an overweight/obese mother is paired with an undernourished child. The nutritional status of children is defined according to WHO 2006 child growth standards as underweight (i.e., low weight-for-age), stunting (i.e., low height-for-age) and wasting (i.e., low weight-for-height). Maternal overweight/obesity (i.e., BMI ≥ 25 kg/m2) is defined using adult BMI criterion. Descriptive, bivariate, and adjusted multivariable logistic regression analysis are conducted.ResultsOf the overweight/obese mothers, 21.3%, 26.5%, and 14% have underweight, stunted, and wasted children respectively. In adjusted models, maternal short stature (aOR: 2.94, 95% CI: 2.30-3.75), age of child (aOR: 3.29, 95% CI: 2.76-3.92), and poorest wealth status (aOR: 2.01, 95% CI: 1.59-2.54) are significant predictors of overweight/obese mothers and stunted child pairs. Similarly, poor wealth status (aOR: 1.68, 95% CI:1.32-2.14), maternal stature (aOR: 2.70, 95% CI: 2.08-3.52), and child aged 2-5 years (aOR: 1.77, 95% CI:1.51-2.08) are also significantly associated with higher occurrence of overweight/obese mother and-underweight child pairs.ConclusionFindings of the study are consistent with the phase of nutrition transition and double burden of malnutrition. The paper concludes with suggestions to improve the socioeconomic condition, more strategic nutrition specific investments and policy interventions to eliminate all forms of malnutrition for achieving SDGs.

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Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition.

Publications

Transgenerational transmission of hedonic behaviors and metabolic phenotypes induced by maternal overnutrition.

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