PMID- 31547311 OWN - NLM STAT- MEDLINE DCOM- 20200131 LR - 20240109 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 24 IP - 18 DP - 2019 Sep 12 TI - Anti-Metabolic Syndrome Effects of Fucoidan from Fucus vesiculosus via Reactive Oxygen Species-Mediated Regulation of JNK, Akt, and AMPK Signaling. LID - 10.3390/molecules24183319 [doi] LID - 3319 AB - Recent studies have reported that dietary fiber improved metabolic syndrome (MetS). However, the effects of fucoidans on MetS were still not clear. In this study, we evaluated the activity of fucoidan from Fucus vesiculosus (FvF) on attenuating MetS and first elucidated the underlying mechanism. In vitro, FvF treatment remarkably lowered the level of reactive oxygen species (ROS) compared with the sodium palmitate (PA)-induced insulin resistance (IR) group. The phosphorylation level of c-Jun N-terminal kinase (JNK) was significantly decreased, while phosphorylation of protein kinase B (pAkt) level increased, compared with that of the HepG2 cells treated with PA. Thus, FvF increased glucose consumption and relieved IR via ROS-mediated JNK and Akt signaling pathways. In addition, these changes were accompanied by the activation of adenosine 5'-monophosphate-ativated protein kinase (AMPK) and its downstream targets (e.g., HMG-CoA reductase (HMGCR), acetyl-CoA carboxylase (ACC), and sterol-regulatory element-binding protein-1c (SREBP-1C)), which improved lipid metabolism in IR HepG2 cells. In vivo, FvF improved hyperglycemia and decreased serum insulin level in mice with MetS. Furthermore, we evaluated the inhibition of glucose transport by in vitro (Caco-2 monolayer model), semi-in vivo (everted gut sac model) and oral glucose tolerance test (OGTT), which indicated that FvF could significantly reduce the absorption of glucose into the blood stream, thus it could improve blood-glucose levels and IR in mice with MetS. Moreover, FvF decreased serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) levels and liver lipid accumulation, while increased the serum high density lipoprotein cholesterol (HDL-C) level in mice with MetS. Therefore, FvF could be considered as a potential candidate for the treatment of MetS by alleviating IR, inhibiting glucose transportation, and regulating lipid metabolism. FAU - Wang, Xueliang AU - Wang X AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. wangsun13141314@126.com. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. wangsun13141314@126.com. FAU - Shan, Xindi AU - Shan X AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. toughraw123@163.com. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. toughraw123@163.com. FAU - Dun, Yunlou AU - Dun Y AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. yiqieshunli0628@163.com. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. yiqieshunli0628@163.com. FAU - Cai, Chao AU - Cai C AUID- ORCID: 0000-0003-4377-3989 AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. caic@ouc.edu.cn. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. caic@ouc.edu.cn. FAU - Hao, Jiejie AU - Hao J AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. 2009haojie@ouc.edu.cn. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. 2009haojie@ouc.edu.cn. FAU - Li, Guoyun AU - Li G AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. liguoyun808@126.com. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. liguoyun808@126.com. FAU - Cui, Kaiyun AU - Cui K AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. littles350786@163.com. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. littles350786@163.com. FAU - Yu, Guangli AU - Yu G AUID- ORCID: 0000-0002-6372-9750 AD - Key Laboratory of Marine Drugs of Ministry of Education, Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. glyu@ouc.edu.cn. AD - Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China. glyu@ouc.edu.cn. LA - eng GR - 31670811/National Natural Science Foundation of China/ GR - 81402982/National Natural Science Foundation of China/ GR - U1606403/NSFC-Shandong Joint Fund for Marine Science Research Centers/ GR - 2016ASKJ08-2/Qingdao National Laboratory for Marine Science and Technology/ GR - TS201511011/Taishan Scholar Project Special Funds/ GR - 2018SDKJ0404/Shandong Provincial Major Science and Technology Innovation Project/ GR - 2018ZX09735-004/National Science and Technology Major Project of China/ PT - Journal Article DEP - 20190912 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Blood Glucose) RN - 0 (Polysaccharides) RN - 0 (Reactive Oxygen Species) RN - 9072-19-9 (fucoidan) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Animals MH - Blood Glucose/metabolism MH - Body Weight/drug effects MH - Disease Models, Animal MH - Fucus/*chemistry MH - Hep G2 Cells MH - Humans MH - Insulin Resistance MH - Lipid Metabolism/drug effects MH - MAP Kinase Signaling System/drug effects MH - Male MH - Metabolic Syndrome/*drug therapy/*metabolism MH - Mice MH - Oxidative Stress/drug effects MH - Polysaccharides/*pharmacology MH - Proto-Oncogene Proteins c-akt/metabolism MH - Reactive Oxygen Species/*metabolism MH - Signal Transduction/drug effects PMC - PMC6767115 OTO - NOTNLM OT - AMPK signaling pathway OT - ROS OT - fucoidan OT - insulin resistance OT - lipid metabolism OT - metabolic syndrome COIS- The authors declare no competing financial interests. EDAT- 2019/09/25 06:00 MHDA- 2020/02/01 06:00 PMCR- 2019/09/12 CRDT- 2019/09/25 06:00 PHST- 2019/08/19 00:00 [received] PHST- 2019/09/07 00:00 [revised] PHST- 2019/09/10 00:00 [accepted] PHST- 2019/09/25 06:00 [entrez] PHST- 2019/09/25 06:00 [pubmed] PHST- 2020/02/01 06:00 [medline] PHST- 2019/09/12 00:00 [pmc-release] AID - molecules24183319 [pii] AID - molecules-24-03319 [pii] AID - 10.3390/molecules24183319 [doi] PST - epublish SO - Molecules. 2019 Sep 12;24(18):3319. doi: 10.3390/molecules24183319.