2. Academic Validation
  3. Oral flavonoid fisetin treatment protects against prolonged high-fat-diet-induced cardiac dysfunction by regulation of multicombined signaling

Oral flavonoid fisetin treatment protects against prolonged high-fat-diet-induced cardiac dysfunction by regulation of multicombined signaling

  • J Nutr Biochem. 2020 Mar;77:108253. doi: 10.1016/j.jnutbio.2019.108253.
Lin-Feng Hu 1,  Jing Feng 1,  Xianling Dai 1,  Yan Sun 1,  Mingxin Xiong 1,  Lili Lai 1,  Shaoyu Zhong 1,  Chao Yi 1,  Geng Chen 1,  Huanhuan Li 1,  Qiufeng Yang 1,  Qin Kuang 1,  Tingting Long 1,  Jianxia Zhan 1,  Tingting Tang 1,  Chenxu Ge 2,  Jun Tan 3,  Minxuan Xu 4
Affiliations

Affiliations

  • 1 Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing 400067, PR China.
  • 2 Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing 400067, PR China. Electronic address: gecxsharon@foxmail.com.
  • 3 Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing 400067, PR China. Electronic address: tanjunmail@126.com.
  • 4 Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, PR China; Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing 400067, PR China. Electronic address: minxuanxu@foxmail.com.
PMID: 31835147 DOI: 10.1016/j.jnutbio.2019.108253
Abstract

Excess high-fat diet (HFD) intake predisposes the occurrence of obesity-associated heart injury, but the mechanism is elusive. Fisetin (FIS), as a natural flavonoid, has potential activities to alleviate obesity-induced metabolic syndrome. However, the underlying molecular mechanisms of FIS against HFD-induced cardiac injury remain unclear. The present study was to explore the protective effects of FIS on cardiac dysfunction in HFD-fed mice. We found that FIS alleviated HFD-triggered metabolic disorder by reducing body weight, fasting blood glucose and Insulin levels, and Insulin resistance. Moreover, FIS supplements significantly alleviated dyslipidemia in both mouse hearts and cardiomyocytes stimulated by metabolic stress. FIS treatment abolished HFD-induced inflammatory response in heart tissues through suppressing TNF receptor-1/TNF receptor-associated factor-2 (Tnfr-1/Traf-2) signaling. Furthermore, FIS induced a strong reduction in the expression of fibrosis-related genes, contributing to the inhibition of fibrosis by inactivating transforming growth factor (Tgf)-β1/Smads/ERK1/2 signaling. Collectively, these results demonstrated that FIS could be a promising therapeutic strategy for the treatment of obesity-associated cardiac injury.

Keywords

Fisetin; Insulin resistance and dyslipidemia; Metabolic syndrome; Tgf-β1/Smads/Erk1/2; Tnfr-1/Traf-2.

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