2. Academic Validation
  3. Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion

Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion

  • Biochim Biophys Acta Mol Basis Dis. 2024 Dec;1870(8):167488. doi: 10.1016/j.bbadis.2024.167488.
Aidi Mou 1,  Fang Sun 1,  Dan Tong 1,  Lijuan Wang 1,  Zongshi Lu 1,  Tingbing Cao 1,  Li Li 1,  Mei You 1,  Qing Zhou 1,  Xiaorong Chen 1,  Jie Xiang 1,  Daoyan Liu 1,  Peng Gao 2,  Hongbo He 1,  Zhiming Zhu 3
Affiliations

Affiliations

  • 1 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing 400042, PR China.
  • 2 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing 400042, PR China. Electronic address: gaopeng1982@tmmu.edu.cn.
  • 3 Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Army Medical University, Chongqing Institute of Hypertension, Chongqing 400042, PR China. Electronic address: zhuzm@tmmu.edu.cn.
PMID: 39218272 DOI: 10.1016/j.bbadis.2024.167488
Abstract

Background: Obesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms.

Methods: The C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of Adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether Adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating Adiponectin secretion.

Results: Apigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased Adiponectin secretion from BAT; knockdown of Adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing Adiponectin expression.

Conclusions: Our study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased Adiponectin levels by inhibiting CD38.

Keywords

Adipose inflammation; Apigenin; Obesity-related hypertension; Transient receptor potential channel vanilla 4 Adiponectin.

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