Exercise attenuates high-fat diet-induced PVAT dysfunction through improved inflammatory response and BMP4-regulated adipose tissue browning

Xiaojie Liu; Xi Jiang; Jing Hu; Mingxing Ding; Sang Ki Lee; Mallikarjuna Korivi; Yongdong Qian; Ting Li; Lifeng Wang; Wei Li

doi:10.3389/fnut.2024.1393343

Exercise attenuates high-fat diet-induced PVAT dysfunction through improved inflammatory response and BMP4-regulated adipose tissue browning

Front Nutr. 2024 May 9:11:1393343. doi: 10.3389/fnut.2024.1393343. eCollection 2024.

Authors

Xiaojie Liu^#¹, Xi Jiang^#¹, Jing Hu², Mingxing Ding², Sang Ki Lee³, Mallikarjuna Korivi¹, Yongdong Qian¹, Ting Li¹, Lifeng Wang¹, Wei Li¹

Affiliations

¹ Exercise and Metabolism Research Center, College of Physical Education and Health Sciences, Zhejiang Normal University, Jinhua, China.
² School of Medicine, Jinhua Polytechnic, Jinhua, China.
³ Department of Sport Science, College of Natural Science, Chungnam National University, Daejeon, Republic of Korea.

^# Contributed equally.

Abstract

Background: Perivascular adipose tissue (PVAT) dysfunction impairs vascular homeostasis. Impaired inflammation and bone morphogenetic protein-4 (BMP4) signaling are involved in thoracic PVAT dysfunction by regulating adipokine secretion and adipocyte phenotype transformation. We investigated whether aerobic exercise training could ameliorate high-fat diet (HFD)-induced PVAT dysfunction via improved inflammatory response and BMP4-mediated signaling pathways.

Methods: Sprague-Dawley rats (n = 24) were divided into three groups, namely control, high-fat diet (HFD), and HFD plus exercise (HEx). After a 6-week intervention, PVAT functional efficiency and changes in inflammatory biomarkers (circulating concentrations in blood and mRNA expressions in thoracic PVAT) were assessed.

Results: Chronic HFD feeding caused obesity and dyslipidemia in rats. HFD decreased the relaxation response of PVAT-containing vascular rings and impaired PVAT-regulated vasodilatation. However, exercise training effectively reversed these diet-induced pathological changes to PVAT. This was accompanied by significantly (p < 0.05) restoring the morphological structure and the decreased lipid droplet size in PVAT. Furthermore, HFD-induced impaired inflammatory response (both in circulation and PVAT) was notably ameliorated by exercise training (p < 0.05). Specifically, exercise training substantially reversed HFD-induced WAT-like characteristics to BAT-like characteristics as evidenced by increased UCP1 and decreased FABP4 protein levels in PVAT against HFD. Exercise training promoted transcriptional activation of BMP4 and associated signaling molecules (p38/MAPK, ATF2, PGC1α, and Smad5) that are involved in browning of adipose tissue. In conjunction with gene expressions, exercise training increased BMP4 protein content and activated downstream cascades, represented by upregulated p38/MAPK and PGC1α proteins in PVAT.

Conclusion: Regular exercise training can reverse HFD-induced obesity, dyslipidemia, and thoracic PVAT dysfunction in rats. The browning of adipose tissue through exercise appears to be modulated through improved inflammatory response and/or BMP4-mediated signaling cascades in obese rats.

Keywords: BMP4; adipose tissue browning; aerobic exercise; cardiovascular disease; high-fat diet.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by Science and Technology Bureau of Jinhua City, grant number 2022-3-136. This study also supported by the Zhejiang Provincial Natural Science Foundation of China, grant number LY19C110002. This study was conducted with financial support from JH, LW, and TL.