PMID- 31731817 OWN - NLM STAT- MEDLINE DCOM- 20200508 LR - 20240109 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 11 IP - 11 DP - 2019 Nov 15 TI - Ecklonia Cava Extract Attenuates Endothelial Cell Dysfunction by Modulation of Inflammation and Brown Adipocyte Function in Perivascular Fat Tissue. LID - 10.3390/nu11112795 [doi] LID - 2795 AB - 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-alpha (TNF-alpha) 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 gamma (PPARgamma) expression. Protective effects against decreased Sirt1 and PPARgamma 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. FAU - Son, Myeongjoo AU - Son M AUID- ORCID: 0000-0002-9104-3991 AD - Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea. AD - 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. FAU - Oh, Seyeon AU - Oh S AD - 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. FAU - Lee, Hye Sun AU - Lee HS AD - 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. FAU - Chung, Dong-Min AU - Chung DM AD - Shinwoo cooperation. Ltd. 991, Worasan-ro, Munsan-eup, Jinju, Gyeongsangnam-do 52839, Korea. FAU - Jang, Ji Tae AU - Jang JT AD - Aqua Green Technology Co., Ltd., Smart Bldg., Jeju Science Park, Cheomdan-ro, Jeju 63309, Korea. FAU - Jeon, You-Jin AU - Jeon YJ AD - Department of Marine Life Science, Jeju National University, Jeju 63243, Korea. FAU - Choi, Chang Hu AU - Choi CH AD - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. FAU - Park, Kook Yang AU - Park KY AD - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. FAU - Son, Kuk Hui AU - Son KH AD - Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Korea. FAU - Byun, Kyunghee AU - Byun K AD - Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea. AD - 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. LA - eng GR - 20170285/Ministry of Oceans and Fisheries/ PT - Journal Article DEP - 20191115 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - 0 (Adiponectin) RN - 0 (Anti-Inflammatory Agents) RN - 0 (Ccl2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Dioxins) RN - 0 (Plant Extracts) RN - 01Y4A2QXY0 (Pyrogallol) RN - 88095-81-2 (6,6'-bieckol) RN - DHD7FFG6YS (Phloroglucinol) SB - IM MH - Adipocytes, Brown/*drug effects MH - Adiponectin/metabolism MH - Adipose Tissue/metabolism MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Chemokine CCL2/metabolism MH - Diet, High-Fat/adverse effects MH - Dioxins/pharmacology MH - Endoplasmic Reticulum Stress/drug effects MH - Endothelial Cells/*drug effects MH - Inflammation MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Peripheral Vascular Diseases/*drug therapy/etiology MH - *Phaeophyceae MH - Phloroglucinol/pharmacology MH - Plant Extracts/*pharmacology MH - Pyrogallol/pharmacology PMC - PMC6893767 OTO - NOTNLM OT - Ecklonia cava OT - brown adipocyte OT - endoplasmic reticulum stress OT - endothelial cell dysfunction OT - inflammation OT - obesity OT - perivascular fat tissue COIS- The authors declare no conflict of interest. EDAT- 2019/11/17 06:00 MHDA- 2020/05/10 06:00 PMCR- 2019/11/01 CRDT- 2019/11/17 06:00 PHST- 2019/10/31 00:00 [received] PHST- 2019/11/12 00:00 [revised] PHST- 2019/11/13 00:00 [accepted] PHST- 2019/11/17 06:00 [entrez] PHST- 2019/11/17 06:00 [pubmed] PHST- 2020/05/10 06:00 [medline] PHST- 2019/11/01 00:00 [pmc-release] AID - nu11112795 [pii] AID - nutrients-11-02795 [pii] AID - 10.3390/nu11112795 [doi] PST - epublish SO - Nutrients. 2019 Nov 15;11(11):2795. doi: 10.3390/nu11112795.