Nutrition has a pervasive impact on cardiac microRNA expression in isogenic mice

Abstract

The complex interaction between obesity, Western-style diets, and cardiovascular disease is of increasing interest, with a growing number of children being born to obese parents with poor lifestyle choices. These offspring have themselves an increased susceptibility to obesity and subsequent cardiovascular disease in adult life, which may be 'programmed' by their intrauterine environment. Cardiac microRNAs (miRNAs) are affected by multiple disease states, and have also been shown to be capable of exerting a hormone-like control on whole body metabolism. Here we sought to determine the effect of prenatal exposure to maternal obesity and/or postnatal exposure to a Western diet on miRNA expression in the heart. Unbiased small RNA sequencing was carried out on cardiac tissue from young adult mice born to lean or obese mothers; offspring were weaned onto either a low-fat control diet or a high-fat Western-style diet. We found 8 cardiac miRNAs that were significantly altered in response to maternal obesity, but only when the offspring were challenged postnatally with the Western diet. In contrast, postnatal exposure to the diet alone induced significant changes to the expression of a much larger number of miRNAs (33 in offspring of lean and 46 in offspring of obese). Many of the affected miRNAs have previously been implicated in various cardiac pathologies. The pervasive cardiac miRNA changes induced by a Western diet suggest that an individual's lifestyle choices outweigh the impact of any programming effects by maternal obesity on miRNA-related cardiac health.

At the heart of programming: the role of micro-RNAs

“…134 In this study, the comparison between prenatal exposure to maternal obesity and/or postnatal exposure to a Western diet on micro-RNA expression profiles showed that many more cardiac micro-RNA implicated in various cardiac pathologies 134 are altered in response to a relatively short period of postnatal overnutrition, rather than by a longer period of prenatal overnutrition. 134 Furthermore, cardiac micro-RNAs not only regulate functions, but also regulate metabolism at the body level. Indeed, miR-208 which cardiac levels are increased in high-fat diet mice, regulates the mediator complex subunit 13 (Med13) involved in the regulation energy balance in the heart.…”

High Fat Programming and Cardiovascular Disease

“…There is an intricate cardiac miRNA network, modulated by HFD administration, and implicated in the pathogenesis of CVD. Poor cardiac outcomes are linked to miRNAs modulated after HFD exposure in mice [ 56 ]. In young adult mouse offspring (12 weeks of age), exposure to maternal obesity altered some cardiac-relevant microRNA (miRNA, small, non-coding endogenous RNAs of 21–25 nucleotides) expression, overlaid on a cardiac miRNAome that was markedly changed after 9 weeks of exposure to a HFD (the HFD mimicked a Western fast-food diet) [ 56 ].…”

“…Poor cardiac outcomes are linked to miRNAs modulated after HFD exposure in mice [ 56 ]. In young adult mouse offspring (12 weeks of age), exposure to maternal obesity altered some cardiac-relevant microRNA (miRNA, small, non-coding endogenous RNAs of 21–25 nucleotides) expression, overlaid on a cardiac miRNAome that was markedly changed after 9 weeks of exposure to a HFD (the HFD mimicked a Western fast-food diet) [ 56 ]. After 9 weeks of the HFD administration, 33 cardiac miRNA expression profiles were altered [ 56 ].…”

“…In young adult mouse offspring (12 weeks of age), exposure to maternal obesity altered some cardiac-relevant microRNA (miRNA, small, non-coding endogenous RNAs of 21–25 nucleotides) expression, overlaid on a cardiac miRNAome that was markedly changed after 9 weeks of exposure to a HFD (the HFD mimicked a Western fast-food diet) [ 56 ]. After 9 weeks of the HFD administration, 33 cardiac miRNA expression profiles were altered [ 56 ]. miR-30 family members were prominent as their dysregulation is associated with cardiac abnormalities and ischemia-reperfusion injury [ 57 ], cardiomyocyte endoplasmic reticulum (ER) stress [ 58 ] and pathological hypertrophy [ 59 , 60 ].…”

Maternal Nutrition and the Problem of Intrauterine Disease Programming in Children

“…В исследованиях на бабуинах, матери которых получали питание, богатое жирами, показана экспрессия микроРНК, вовлеченной в эпигенетическую регуляцию активности сердечно-сосудистой системы и метаболизма [61,62]. В других исследованиях, также проведенных на приматах, продемонстрировано существенное влияние подобного питания матери на метаболизм глюкозы и концентрацию инсулина в плазме крови потомства [63,64].…”