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Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats.

ABSTRACT: Background:Ketogenic diet (KD) has been proposed to be an effective lifestyle intervention in metabolic syndrome. However, the effects of KD on cardiac remodeling have not been investigated. Our aim was to investigate the effects and the underling mechanisms of KD on cardiac remodeling in spontaneously hypertensive rats (SHRs). Methods:10-week-old spontaneously hypertensive rats were subjected to normal diet or ketogenic diet for 4 weeks. Then, their blood pressure and cardiac remodeling were assessed. Cardiac fibroblasts were isolated from 1- to 3-day-old neonatal pups. The cells were then cultured with ketone body with or without TGF-? to investigate the mechanism in vitro. Results:4 weeks of KD feeding aggravated interstitial fibrosis and cardiac remodeling in SHRs. More interestingly, ketogenic diet feeding increased the activity of mammalian target of rapamyoin (mTOR) complex 2 pathway in the heart of SHRs. In addition, ?-hydroxybutyrate strengthened the progression of TGF-?-induced fibrosis in isolated cardiac fibroblasts. mTOR inhibition reversed this effect, indicating that ketone body contributes to cardiac fibroblasts via mTOR pathway. Conclusions:These data suggest that ketogenic diet may lead to adverse effects on the remodeling in the hypertensive heart, and they underscore the necessity to fully evaluate its reliability before clinical use.

SUBMITTER: You Y

PROVIDER: S-EPMC7586698 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats.

You Yuehua Y Guo Yongzheng Y Jia Ping P Zhuang Biaobiao B Cheng Yu Y Deng Hongpei H Wang Xiaowen X Zhang Cheng C Luo Suxin S Huang Bi B

Nutrition & metabolism 20201026

<h4>Background</h4>Ketogenic diet (KD) has been proposed to be an effective lifestyle intervention in metabolic syndrome. However, the effects of KD on cardiac remodeling have not been investigated. Our aim was to investigate the effects and the underling mechanisms of KD on cardiac remodeling in spontaneously hypertensive rats (SHRs).<h4>Methods</h4>10-week-old spontaneously hypertensive rats were subjected to normal diet or ketogenic diet for 4 weeks. Then, their blood pressure and cardiac rem ...[more]

PMID: 33117428

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Project description:BACKGROUND:The combination of systemic arterial hypertension and diabetes mellitus (DM) induces greater cardiac remodeling than either condition alone. However, this association has been poorly addressed in senescent rats. Therefore, this study aimed to analyze the influence of streptozotocin-induced DM on ventricular remodeling and oxidative stress in aged spontaneously hypertensive rats (SHR). METHODS:Fifty 18 month old male SHR were divided into two groups: control (SHR, n?=?25) and diabetic (SHR-DM, n?=?25). DM was induced by streptozotocin (40 mg/kg, i.p.). After nine weeks, the rats underwent echocardiography and myocardial functional study in left ventricular (LV) isolated papillary muscle preparations. LV samples were obtained to measure myocyte diameters, interstitial collagen fraction, and hydroxyproline concentration. Gene expression of atrial natriuretic peptide (ANP) and ?- and ?-myosin heavy chain (MyHC) isoforms was evaluated by RT-PCR. Serum oxidative stress was assessed by measuring lipid hydroperoxide concentration and superoxide dismutase and glutathione peroxidase activities. STATISTICS:Student's t test or Mann-Whitney test, p?<?0.05. RESULTS:SHR-DM presented higher blood glucose (487?±?29 vs. 89.1?±?21.1 mg/dL) and lower body weight (277?±?26 vs. 339?±?38 g). Systolic blood pressure did not differ between groups. Echocardiography showed LV and left atrial dilation, LV diastolic and relative wall thickness decrease, and LV systolic and diastolic function impairment in SHR-DM. Papillary muscle study showed decreased myocardial contractility and contractile reserve in SHR-DM. Myocyte diameters and myocardial interstitial collagen fraction and hydroxyproline concentration did not differ between groups. Increased serum pro-oxidant activity and gene expression of ANP and ?/?-MyHC ratio were observed in DM. CONCLUSION:Diabetes mellitus induces cardiac dilation and functional impairment, increases oxidative stress and activates fetal gene program in aged spontaneously hypertensive rats.

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Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats.

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Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats.

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