Maternal obesity regulates gene expression in the hearts of offspring

Raipuria, Mukesh; Hardy, Georgia; Bahari, Hasnah; Morris, Margaret J.

doi:10.1016/j.numecd.2015.05.011

Cited by 11 publications

(7 citation statements)

References 33 publications

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“…Myocardial fibrosis and remodeling occur under various adverse stimuli, accompanied by systolic and diastolic dysfunction, arrhythmia and adverse outcomes (Frangogiannis, 2019). Alarmingly, obesity alters gene expression in the heart of offspring (Raipuria et al, 2015). Emerging evidence has demonstrated that obesity is associated with chronic low-grade inflammation because excessive fat causes abnormal function and increases the level of systemic proinflammatory factors (Deng et al, 2016; Shan et al, 2017), that are associated with the progression of pathophysiological processes such as myocardial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Aerobic Exercise Ameliorates Myocardial Inflammation, Fibrosis and Apoptosis in High-Fat-Diet Rats by Inhibiting P2X7 Purinergic Receptors

Chen

Wang

et al. 2019

Front. Physiol.

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BackgroundHigh-fat-diet (HFD) is associated with chronic low-grade inflammation. P2X7 purinergic receptors (P2X7R) are key regulators of inflammasome activation. The benefits of exercise are partly attributed to its anti-inflammatory effect, but whether it regulates P2X7R expression to improve remodeling in cardiac myocytes treated by HFD is not completely clarified.MethodsThree groups of Sprague-Dawley (SD) rats were studied: (1) control group (fed a normal chow diet), (2) HFD group, and (3) HFD+ exercise group. H9c2 myocytes were pretreated with or without A438079 (a P2X7R inhibitor) and then exposed to 200 μM palmitic acid (PA) for 24 h. The levels of mRNA and protein were measured by real-time PCR and Western blot, respectively. Masson staining and hematoxylin-eosin (HE) staining were used to identify remodeling of the heart. The concentration of IL-1β in serum or supernatants were measured by ELISA.ResultsIn vivo, collagen deposition and the number of disordered cells significantly increased in the hearts of the HFD group compared to the control group. However, exercise markedly reversed these changes in the myocardium, and the same trends were observed in the expression of MMP9, collagen I and TGF-β. Notably, the expression of P2X7R, NLRP3, caspase-1 in the hearts, and serum IL-1β level were also greatly upregulated in the heart of the HFD diet rats, and all these changes were ameliorated in the HFD + EX group. As expected, exercise also reduced the number of TUNEL-positive cells, which was consistent with the caspase-3, Bax, and Bcl-2 results. Moreover, exercise reduced body weight and blood lipid concentrations in the HFD diet rats. In vitro, we observed that the hallmark of fibrosis, inflammation and apoptosis in H9c2 myocytes enhanced by PA, and the P2X7R inhibitor treatment significantly reduced the expression of the NLRP3, caspase-1, suppressed the secretion of IL-1β of H9c2 cells, inhibited collagen I, TGF-β, MMP9, Bax, caspase-3 levels and increased the expression of Bcl-2, compared with the PA group. In addition, a decrease of the number of TUNEL-positive cells used by A438079 further support that cardiomyocytes apoptosis could be inhibited.ConclusionAerobic exercise reversed the cardiac remodeling via the reduction of inflammation, fibrosis and apoptosis in HFD rats, at least in part through inhibiting P2X7R expression in cardiomyocytes.

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Section: Introductionmentioning

confidence: 99%

Aerobic Exercise Ameliorates Myocardial Inflammation, Fibrosis and Apoptosis in High-Fat-Diet Rats by Inhibiting P2X7 Purinergic Receptors

Chen

Wang

et al. 2019

Front. Physiol.

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“…The increasing prevalence of obesity leads to an increased risk of several other non-communicable diseases including type 2 diabetes, cardiovascular disease, some cancers, respiratory conditions, fatty liver disease, reproductive disorders, depression, and other mental health conditions ( Gonçalves et al, 2012 ; Morris et al, 2014 ). Furthermore recent studies on maternal obesity have revealed the alarming metabolic impact on offspring, including increased risk for obesity ( Borengasser et al, 2014 ; Catalano, 2015 ; Raipuria et al, 2015 ), highlighting the importance of testing interventions in obese females.…”

Section: Introductionmentioning

confidence: 99%

Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice

et al. 2016

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Obesity is well known to be a major cause of several chronic metabolic diseases, which can be partially counteracted by exercise. This is due, in part, to an upregulation of mitochondrial activity through increased nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that NAD+ levels can be increased by using the NAD+ precursor, nicotinamide mononucleotide (NMN) leading to the suggestion that NMN could be a useful intervention in diet related metabolic disorders. In this study we compared the metabolic, and especially mitochondrial-associated, effects of exercise and NMN in ameliorating the consequences of high-fat diet (HFD) induced obesity in mice. Sixty female 5 week old C57BL6/J mice were allocated across five groups: Chow sedentary: CS; Chow exercise: CEX; HFD sedentary: HS; HFD NMN: HNMN; HFD exercise: HEX (12/group). After 6 weeks of diet, exercise groups underwent treadmill exercise (15 m/min for 45 min), 6 days per week for 6 weeks. NMN or vehicle (500 mg/kg body weight) was injected (i.p.) daily for the last 17 days. No significant alteration in body weight was observed in response to exercise or NMN. The HFD significantly altered adiposity, glucose tolerance, plasma insulin, NADH levels and citrate synthase activity in muscle and liver. HEX and HNMN groups both showed significantly improved glucose tolerance compared to the HS group. NAD+ levels were increased significantly both in muscle and liver by NMN whereas exercise increased NAD+ only in muscle. Both NMN and exercise ameliorated the HFD-induced reduction in liver citrate synthase activity. However, exercise, but not NMN, ameliorated citrate synthase activity in muscle. Overall these data suggest that while exercise and NMN-supplementation can induce similar reversal of the glucose intolerance induced by obesity, they are associated with tissue-specific effects and differential alterations to mitochondrial function in muscle and liver.

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“…71 Interestingly, maternal obesity due to high-fat diet during pregnancy and lactation results in a decrease in bitter taste receptors in hearts of rats. 72 The decrease in these receptors might increase offspring risk of cardiovascular diseases in adulthood. In addition, maternal overnutrition induces an epigenetic modification of the hypothalamic anorexigenic neuropeptide proopiomelanocortin (POMC) gene.…”

Section: Dietmentioning

confidence: 99%

“…Bitter taste receptors have recently been proved to be in the heart and agonists of these receptors cause relaxation of heart muscles, reduced ventricular pressure and increased pressure of the aorta 71 . Interestingly, maternal obesity due to high-fat diet during pregnancy and lactation results in a decrease in bitter taste receptors in hearts of rats 72 . The decrease in these receptors might increase offspring risk of cardiovascular diseases in adulthood.…”

Section: Passive Strategy Against Ncds: Negative In Utero Programmingmentioning

confidence: 99%

Strategies to reduce non-communicable diseases in the offspring: negative and positivein uteroprogramming

Rodriguez-Caro

Williams

2018

J Dev Orig Health Dis

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Non-communicable diseases (NCDs) are a major problem as they are the leading cause of death and represent a substantial economic cost. The 'Developmental Origins of Health and Disease Hypothesis' proposes that adverse stimuli at different life stages can increase the predisposition to these diseases. In fact, adverse in utero programming is a major origin of these diseases due to the high malleability of embryonic development. This review provides a comprehensive analysis of the scientific literature on in utero programming and NCDs highlighting potential medical strategies to prevent these diseases based upon this programming. We fully address the concept and mechanisms involved in this programming (anatomical disruptions, epigenetic modifications and microbiota alterations). We also examine the negative role of in utero programming on the increased predisposition of NCDs in the offspring, which introduces the passive medical approach that consists of avoiding adverse stimuli including an unhealthy diet and environmental chemicals. Finally, we extensively discuss active medical approaches that target the causes of NCDs and have the potential to significantly and rapidly reduce the incidence of NCDs. These approaches can be classified as direct in utero programming modifications and personalized lifestyle pregnancy programs; they could potentially provide transgenerational NCDs protection. Active strategies against NCDs constitute a promising tool for the reduction in NCDs.

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Maternal obesity regulates gene expression in the hearts of offspring

Cited by 11 publications

References 33 publications

Aerobic Exercise Ameliorates Myocardial Inflammation, Fibrosis and Apoptosis in High-Fat-Diet Rats by Inhibiting P2X7 Purinergic Receptors

Aerobic Exercise Ameliorates Myocardial Inflammation, Fibrosis and Apoptosis in High-Fat-Diet Rats by Inhibiting P2X7 Purinergic Receptors

Head to Head Comparison of Short-Term Treatment with the NAD+ Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice

Strategies to reduce non-communicable diseases in the offspring: negative and positivein uteroprogramming

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