@article {Jeongmol.113.085100, author = {Yong-Tae Jeong and Yong Deuk Kim and Young-Mi Jung and Dong-Chan Park and Dong-Sub Lee and Sae-Kwang Ku and Xian Li and Yue Lu and Guang Hsuan Chao and Keuk-Jun Kim and Jai-Youl Lee and Moon-Chang Baek and Wonku Kang and Seung-Lark Hwang and Hyeun Wook Chang}, title = {Low Molecular Weight Fucoidan (LMWF) Improves ER Stress-Reduced Insulin Sensitivity through AMPK Activation in L6 Myotubes and Restores Lipid Homeostasis in a Mouse Model of Type 2 Diabetes}, elocation-id = {mol.113.085100}, year = {2013}, doi = {10.1124/mol.113.085100}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Low molecular weight fucoidan (LMWF) is widely used to treat metabolic disorders, but its physiologic effects have not been well determined. In the present study, we investigated the metabolic effects of LMWF in db/db mice and the underlying molecular mechanisms involved in endoplasmic reticulum (ER) stress-responsive L6 myotubes. The effect of LMWF-mediated AMP-activated protein kinase (AMPK) activation on insulin resistance via regulation of the ER stress-dependent pathway was examined in vitro and in vivo. In db/db mice, LMWF markedly reduced serum glucose, triglyceride, cholesterol, and LDL levels, and gradually reduced body weights by reducing lipid parameters. Furthermore, it effectively ameliorated glucose homeostasis by elevating glucose tolerance. In addition, the phosphorylation level of AMPK and Akt were markedly reduced by ER stressor, and subsequently, glucose uptake and fatty acid oxidation were also reduced. However, these adverse effects of ER stress were significantly ameliorated by LMWF. Finally, in L6 myotubes, LMWF markedly reduced the ER stress-induced upregulation of mammalian target of rapamycin (mTOR)-p70S61 kinase (S6K) network and subsequently improved the action of insulin via AMPK stimulation. Our findings suggest that AMPK activation by LMWF could prevent metabolic diseases by controlling the ER stress-dependent pathway and that this beneficial effect of LMWF provides a potential therapeutic strategy for ameliorating ER stress-mediated metabolic dysfunctions.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/early/2013/05/08/mol.113.085100}, eprint = {https://molpharm.aspetjournals.org/content/early/2013/05/08/mol.113.085100.full.pdf}, journal = {Molecular Pharmacology} }