Habitual Daily Intake of Fried Foods Raises Transgenerational Inheritance Risk of Heart Failure Through NOTCH1-Triggered Apoptosis

Author:

Wang Anli1,Wan Xuzhi1,Zhu Fanghuan1,Liu Haoyin2,Song Xiaoran1,Huang Yingyu1,Zhu Li1,Ao Yang2,Zeng Jia1,Wang Binjie3,Wu Yuanzhao3,Xu Zhongshi3,Wang Jiye3,Yao Weixuan3,Li Haoyu1,Zhuang Pan1,Jiao Jingjing2,Zhang Yu1ORCID

Affiliation:

1. Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine; Zhejiang Key Laboratory for Agro-Food Processing, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, Zhejiang, China.

2. Department of Endocrinology, The Second Affiliated Hospital, Department of Nutrition, School of Public Health, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.

3. Key Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Department of Criminal Science and Technology, Zhejiang Police College, Hangzhou, Zhejiang, China.

Abstract

Consumption of fried foods is highly prevalent in the Western dietary pattern. Western diet has been unfavorably linked with high risk of developing cardiovascular diseases. Heart failure (HF) as a cardiovascular disease subtype is a growing global pandemic with high morbidity and mortality. However, the causal relationship between long-term fried food consumption and incident HF remains unclear. Our population-based study revealed that frequent fried food consumption is strongly associated with 15% higher risk of HF. The causal relationship may be ascribed to the dietary acrylamide exposure in fried foods. Further cross-sectional study evidenced that acrylamide exposure is associated with an increased risk of HF. Furthermore, we discover and demonstrate that chronic acrylamide exposure may induce HF in zebrafish and mice. Mechanistically, we reveal that acrylamide induces energy metabolism disturbance in heart due to the mitochondria dysfunction and metabolic remodeling. Moreover, acrylamide exposure induces myocardial apoptosis via inhibiting NOTCH1-phosphatidylinositol 3-kinase/AKT signaling. In addition, acrylamide exposure could affect heart development during early life stage, and the adverse effect of acrylamide exposure is a threat for next generation via epigenetic change evoked by DNA methyltransferase 1 (DNMT1). In this study, we reveal the adverse effects and underlying mechanism of fried foods and acrylamide as a typical food processing contaminant on HF from population-based observations to experimental validation. Collectively, these results both epidemiologically and mechanistically provide strong evidence to unravel the mechanism of acrylamide-triggered HF and highlight the significance of reducing fried food consumption for lower the risk of HF.

Funder

National Key Research and Development Program of China

Publisher

American Association for the Advancement of Science (AAAS)

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