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Ketogenic diet aggravates cardiac remodeling in adult spontaneously hypertensive rats
Nutrition & Metabolism ( IF 3.9 ) Pub Date : 2020-10-26 , DOI: 10.1186/s12986-020-00510-7
Yuehua You 1 , Yongzheng Guo 1 , Ping Jia 1 , Biaobiao Zhuang 1 , Yu Cheng 2 , Hongpei Deng 2 , Xiaowen Wang 3 , Cheng Zhang 3 , Suxin Luo 1 , Bi Huang 1
Affiliation  

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). 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-β to investigate the mechanism in vitro. 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, 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. 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.

中文翻译:

生酮饮食加重成年自发性高血压大鼠心脏重塑

生酮饮食 (KD) 已被提议作为一种有效的生活方式干预代谢综合征。然而,尚未研究 KD 对心脏重塑的影响。我们的目的是研究 KD 对自发性高血压大鼠 (SHR) 心脏重塑的影响和潜在机制。10周龄自发性高血压大鼠正常饮食或生酮饮食4周。然后,评估他们的血压和心脏重塑。从 1 至 3 天大的新生幼崽中分离出心脏成纤维细胞。然后将细胞与含有或不含TGF-β的酮体一起培养,以研究体外机制。4 周的 KD 喂养加重了 SHR 的间质纤维化和心脏重塑。更有趣的是,生酮饮食喂养增加了 SHR 心脏中哺乳动物雷帕霉素靶蛋白 (mTOR) 复合物 2 通路的活性。此外,β-羟基丁酸加强了 TGF-β 诱导的离体心脏成纤维细胞纤维化的进展。mTOR 抑制逆转了这种作用,表明酮体通过 mTOR 通路促进心脏成纤维细胞。这些数据表明生酮饮食可能对高血压心脏的重塑产生不利影响,它们强调了在临床使用前充分评估其可靠性的必要性。
更新日期:2020-10-27
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