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Programmed increases in LXR? induced by paternal alcohol use enhance offspring metabolic adaptation to high-fat diet induced obesity.

ABSTRACT: OBJECTIVES:Paternally inherited alterations in epigenetic programming are emerging as relevant factors in numerous disease states, including the growth and metabolic defects observed in fetal alcohol spectrum disorders. In rodents, chronic paternal alcohol use induces fetal growth restriction, as well as sex-specific alterations in insulin signaling and lipid homeostasis in the offspring. Based on previous studies, we hypothesized that the observed metabolic irregularities are the consequence of paternally inherited alterations liver x receptor (LXR) activity. METHODS:Male offspring of alcohol-exposed sires were challenged with a high-fat diet and the molecular pathways controlling glucose and lipid homeostasis assayed for LXR-induced alterations. RESULTS:Similar to findings in studies employing LXR agonists we found that the male offspring of alcohol-exposed sires display resistance to diet-induced obesity and improved glucose homeostasis when challenged with a high-fat diet. This improved metabolic adaptation is mediated by LXR? trans-repression of inflammatory cytokines, releasing IKK? inhibition of the insulin signaling pathway. Interestingly, paternally programmed increases in LXR? expression are liver-specific and do not manifest in the pancreas or visceral fat. CONCLUSIONS:These studies identify LXR? as a key mediator of the long-term metabolic alterations induced by preconception paternal alcohol use.

SUBMITTER: Chang RC

PROVIDER: S-EPMC6807343 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Programmed increases in LXRα induced by paternal alcohol use enhance offspring metabolic adaptation to high-fat diet induced obesity.

Chang Richard C RC Thomas Kara N KN Bedi Yudhishtar S YS Golding Michael C MC

Molecular metabolism 20191003

<h4>Objectives</h4>Paternally inherited alterations in epigenetic programming are emerging as relevant factors in numerous disease states, including the growth and metabolic defects observed in fetal alcohol spectrum disorders. In rodents, chronic paternal alcohol use induces fetal growth restriction, as well as sex-specific alterations in insulin signaling and lipid homeostasis in the offspring. Based on previous studies, we hypothesized that the observed metabolic irregularities are the conseq ...[more]

PMID: 31767168

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Project description:The increase in high-energy dietary intakes is a well-known risk factor for many diseases, and can also negatively impact the tendon. Ancestral lifestyle can mitigate the metabolic harmful effects of offspring exposed to high-fat diet (HF). However, the influence of paternal exercise on molecular pathways associated to offspring tendon remodeling remains to be determined. We investigated the effects of 8 weeks of paternal resistance training (RT) on offspring tendon proteome exposed to standard diet or HF diet. Wistar rats were randomly divided into two groups: sedentary fathers and trained fathers (8 weeks, three times per week, with 8-12 dynamic movements per climb in a stair climbing apparatus). The offspring were obtained by mating with sedentary females. Upon weaning, male offspring were divided into four groups (five animals per group): offspring from sedentary fathers were exposed either to control diet (SFO-C), or to high-fat diet (SFO-HF); offspring from trained fathers were exposed to control diet (TFO-C) or to a high-fat diet (TFO-HF). The Nano-LC-MS/MS analysis revealed 383 regulated proteins among offspring groups. HF diet induced a decrease of abundance in tendon proteins related to extracellular matrix organization, transport, immune response and translation. On the other hand, the changes in the offspring tendon proteome in response to paternal RT were more pronounced when the offspring were exposed to HF diet, resulting in positive regulation of proteins essential for the maintenance of tendon integrity. Most of the modulated proteins are associated to biological pathways related to tendon protection and damage recovery, such as extracellular matrix organization and transport. The present study demonstrated that the father's lifestyle could be crucial for tendon homeostasis in the first generation. Our results provide important insights into the molecular mechanisms involved in paternal intergenerational effects and potential protective outcomes of paternal RT.

Dataset Information

Programmed increases in LXR? induced by paternal alcohol use enhance offspring metabolic adaptation to high-fat diet induced obesity.

Publications

Programmed increases in LXRα induced by paternal alcohol use enhance offspring metabolic adaptation to high-fat diet induced obesity.

Similar Datasets

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