Abstract
BackgroundKetogenic 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).Methods10-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-β to investigate the mechanism in vitro.Results4 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, β-hydroxybutyrate strengthened the progression of TGF-β-induced fibrosis in isolated cardiac fibroblasts. mTOR inhibition reversed this effect, indicating that ketone body contributes to cardiac fibroblasts via mTOR pathway.ConclusionsThese 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.
Highlights
Hypertension is one of the most prevalent chronic diseases and has been the most important risk factor for cardiovascular diseases worldwide [1], including stroke, heart failure, and aneurysm, etc. [2]
Strong evidence has suggested that the mammalian target of rapamyoin overactivation plays important roles in the fibrosis process, and suppressing mTOR is a target for preventing hypertension and its related fibrosis [14]. mTOR is a serine/threonine kinase belonging to Phosphatidylinositol 3 kinase (PI3K) ([phosphoinositide 3-kinase]-related kinase family), which could integrate energy, nutrient and growth factor signals to regulate cell proliferation, cell growth and inflammatory responses [15]
Our previous study reported that ketogenic diet could activate the phosphorylation of Protein kinase B (Akt) in diabetic mice, which indicates that Ketogenic diet (KD) may contribute to the activation of mTOR pathway and exert adverse effects on cardiac remodeling [9]
Summary
Hypertension is one of the most prevalent chronic diseases and has been the most important risk factor for cardiovascular diseases worldwide [1], including stroke, heart failure, and aneurysm, etc. [2]. Hypertension is one of the most prevalent chronic diseases and has been the most important risk factor for cardiovascular diseases worldwide [1], including stroke, heart failure, and aneurysm, etc. Many pathological processes and signal pathways are involved in the development of cardiac remodeling in hypertension [12, 13]. Our previous study reported that ketogenic diet could activate the phosphorylation of Akt in diabetic mice, which indicates that KD may contribute to the activation of mTOR pathway and exert adverse effects on cardiac remodeling [9]. In the present study, we investigated the effects of KD on cardiac remodeling and mTOR pathway in hypertensive rats. Our aim was to investigate the effects and the underling mechanisms of KD on cardiac remodeling in spontaneously hypertensive rats (SHRs)
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