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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:Chitosan oligosaccharides (COS) play a prebiotic role in many ways, whereas its function on microbiota is not fully understood. In this study, the effects of COS on metabolic syndrome were initially investigated by testing changes in the physiological indicators after adding COS to the diet of mice with high fat (group H) and low fat (group L). The results showed that COS markedly inhibited the accumulation of body weight and liver fat induced by high-fat diet, as well as restored the elevated concentration of blood glucose and fasting insulin to normal levels. Next, changes of the murine intestinal microbiota were examined. The results exhibited that COS reduced with-in-sample diversity, while the between-sample microbial diversity enhanced. Specifically, COS enriched Clostridium paraputrificum and Clostridium ramosum in the mice on a high-fat diet, while the abundance of Clostridium cocleatum was reduced. As a comparison, Parabacteroides goldsteinii and Bacteroides uniformis increased their abundance in response to COS in the low-fat diet group. Noticeably, a large amount of Akkermansia muciniphila was enriched in both high-fat or low-fat diet groups. Among the differential fecal bacteria, Clostridium ramosume was found to be positively interacted with Faecalibacterim prausnitzii and Clostridium paraputrificum; Clostridium paraputrificum had a positive interactions with Lactococcus chungangensis and Bifidobacterium mongoliense, suggesting that COS probably ameliorate metabolic syndrome through the microbiota in view of the lipid-lowering effects of these interacted bacteria. Furthermore, the gene expression data revealed that COS improved the functions related to intestinal barrier and glucose transport, which could be the trigger and consequence of the variations in gut microbiota induced by COS. Additionally, correlation analysis found that intestinal bacteria are related to physiological parameters, which further supports the mediating role of gut microbiota in the beneficial effect of COS. In summary, our research results provide new evidence for the prebiotic effects of COS.

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.

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

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