PMID- 24857031 OWN - NLM STAT- MEDLINE DCOM- 20150331 LR - 20140806 IS - 1873-4847 (Electronic) IS - 0955-2863 (Linking) VI - 25 IP - 9 DP - 2014 Sep TI - Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells. PG - 903-13 LID - S0955-2863(14)00082-5 [pii] LID - 10.1016/j.jnutbio.2014.04.001 [doi] AB - Autophagy, a lysosomal pathway to maintain cellular homeostasis, is mediated via the mammalian target of rapamycin (mTOR)-dependent pathways. Hepatic stellate cells (HSCs), previously termed fat- or vitamin A-storing cells, can transdifferentiate into myofibroblast-like cells and are the most relevant cell type for overproduction of extracellular matrix (ECM) and development of liver fibrosis during injury. However, the role of autophagy in fat metabolism of HSCs remains unclear. This study investigates the regulatory effect of natural compounds on fatty acid-induced autophagy pathways of nonchemical-induced HSC (NHSC) and thioacetamide-induced HSC. Oleic acid (OA) and palmitic acid (PA) have shown a significant effect on cell proliferation with oil red O staining and Western blot confirming that OA and PA induce fat storage ability and autophagy protein expression in NHSC. Natural compounds rutin, curcumin, antroquinonol and benzyl cinnamate treatment have shown no effect on the autophagy protein expression. Nevertheless, cells pretreated with OA and PA then treated with rutin, curcumin, antroquinonol and benzyl cinnamate could significantly induce the light chain I/II (LC3 I/II) protein expression. In mTOR-dependent pathway, the PI3K-Class I, Akt, and p-mTOR proteins were decreased with PA treatment. However, there were no significant changes in PI3K-Class III and Beclin-1 protein expressions found to imply that this autophagy is unrelated to the mTOR-independent pathway. Taken together, the present study unveils rutin and curcumin as a possible effective stimulation for fatty acid-induced autophagy via mTOR-dependent pathways in NHSC. We further suggest the benefits of these natural compounds for alleviating liver fibrosis. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Lee, Kuan-Wei AU - Lee KW AD - Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan. FAU - Thiyagarajan, Varadharajan AU - Thiyagarajan V AD - Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan. FAU - Sie, Huei-Wun AU - Sie HW AD - Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan. FAU - Cheng, Ming-Fan AU - Cheng MF AD - Division of Histological and Clinical Pathology, Hualian Army Forces General Hospital, Hualien, Taiwan. FAU - Tsai, May-Jywan AU - Tsai MJ AD - Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Chia, Yi-Chen AU - Chia YC AD - Department of Food Technology, Tajen University, Pingtung, Taiwan. FAU - Weng, Ching-Feng AU - Weng CF AD - Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140424 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Biological Products) RN - 0 (Fatty Acids) RN - 0 (Lipids) SB - IM MH - Animals MH - Autophagy/*drug effects MH - Biological Products/*pharmacology MH - Cells, Cultured MH - Drug Synergism MH - Fatty Acids/*pharmacology MH - Hepatic Stellate Cells/*drug effects/immunology/metabolism MH - Lipids/biosynthesis MH - Male MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - Autophagy OT - Hepatic stellate cells OT - Liver fibrosis OT - Natural compounds OT - mTOR EDAT- 2014/05/27 06:00 MHDA- 2015/04/01 06:00 CRDT- 2014/05/27 06:00 PHST- 2013/11/07 00:00 [received] PHST- 2014/03/23 00:00 [revised] PHST- 2014/04/06 00:00 [accepted] PHST- 2014/05/27 06:00 [entrez] PHST- 2014/05/27 06:00 [pubmed] PHST- 2015/04/01 06:00 [medline] AID - S0955-2863(14)00082-5 [pii] AID - 10.1016/j.jnutbio.2014.04.001 [doi] PST - ppublish SO - J Nutr Biochem. 2014 Sep;25(9):903-13. doi: 10.1016/j.jnutbio.2014.04.001. Epub 2014 Apr 24.