Ecklonia Cava Extract Attenuates Endothelial Cell Dysfunction by Modulation of Inflammation and Brown Adipocyte Function in Perivascular Fat Tissue
by
Myeongjoo Son 1,2,†
, Seyeon Oh 2,†, Hye Sun Lee 2, Dong-Min Chung 3, Ji Tae Jang 4, You-Jin Jeon 5, Chang Hu Choi 6, Kook Yang Park 6, Kuk Hui Son 6,* and Kyunghee Byun 1,2,*
Myeongjoo Son 1,2,†, Seyeon Oh 2,†, Hye Sun Lee 2, Dong-Min Chung 3, Ji Tae Jang 4, You-Jin Jeon 5, Chang Hu Choi 6, Kook Yang Park 6, Kuk Hui Son 6,* and Kyunghee Byun 1,2,*
1
Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea
2
Functional Cellular Networks Laboratory, College of Medicine, Department of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea
3
Shinwoo cooperation. Ltd. 991, Worasan-ro, Munsan-eup, Jinju, Gyeongsangnam-do 52839, Korea
4
Aqua Green Technology Co., Ltd., Smart Bldg., Jeju Science Park, Cheomdan-ro, Jeju 63309, Korea
5
Department of Marine Life Science, Jeju National University, Jeju 63243, Korea
6
Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea
*
Authors to whom correspondence should be addressed.
†
These authors equally contributed to the paper.
Nutrients 2019, 11(11), 2795; https://doi.org/10.3390/nu11112795
Received: 31 October 2019 / Revised: 12 November 2019 / Accepted: 13 November 2019 / Published: 15 November 2019
(This article belongs to the Special Issue Dietary Polyphenols and Cardiometabolic Diseases)
It is well known that perivascular fat tissue (PVAT) dysfunction can induce endothelial cell (EC) dysfunction, an event which is related with various cardiovascular diseases. In this study, we evaluated whether Ecklonia cava extract (ECE) and pyrogallol-phloroglucinol-6,6-bieckol (PPB), one component of ECE, could attenuate EC dysfunction by modulating diet-induced PVAT dysfunction mediated by inflammation and ER stress. A high fat diet (HFD) led to an increase in the number and size of white adipocytes in PVAT; PPB and ECE attenuated those increases. Additionally, ECE and PPB attenuated: (i) an increase in the number of M1 macrophages and the expression level of monocyte chemoattractant protein-1 (MCP-1), both of which are related to increases in macrophage infiltration and induction of inflammation in PVAT, and (ii) the expression of pro-inflammatory cytokines (e.g., tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, chemerin) in PVAT which led to vasoconstriction. Furthermore, ECE and PPB: (i) enhanced the expression of adiponectin and IL-10 which had anti-inflammatory and vasodilator effects, (ii) decreased HFD-induced endoplasmic reticulum (ER) stress and (iii) attenuated the ER stress mediated reduction in sirtuin type 1 (Sirt1) and peroxisome proliferator-activated receptor γ (PPARγ) expression. Protective effects against decreased Sirt1 and PPARγ expression led to the restoration of uncoupling protein -1 (UCP-1) expression and the browning process in PVAT. PPB or ECE attenuated endothelial dysfunction by enhancing the pAMPK-PI3K-peNOS pathway and reducing the expression of endothelin-1 (ET-1). In conclusion, PPB and ECE attenuated PVAT dysfunction and subsequent endothelial dysfunction by: (i) decreasing inflammation and ER stress, and (ii) modulating brown adipocyte function.
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Keywords:
obesity; Ecklonia cava; perivascular fat tissue; brown adipocyte; endothelial cell dysfunction; endoplasmic reticulum stress; inflammation
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MDPI and ACS Style
Son, M.; Oh, S.; Lee, H.S.; Chung, D.-M.; Jang, J.T.; Jeon, Y.-J.; Choi, C.H.; Park, K.Y.; Son, K.H.; Byun, K. Ecklonia Cava Extract Attenuates Endothelial Cell Dysfunction by Modulation of Inflammation and Brown Adipocyte Function in Perivascular Fat Tissue. Nutrients 2019, 11, 2795.
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