title: Synergistic effect of natural compounds on the fatty acid-induced autophagy of activated hepatic stellate cells.
abstract: 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.
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Kuan-Wei
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Varadharajan
authors.initials: V
authors.lastname: Thiyagarajan
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Huei-Wun
authors.initials: HW
authors.lastname: Sie
authors.affiliation: Division of Histological and Clinical Pathology, Hualian Army Forces General Hospital, Hualien, Taiwan.
authors.forename: Ming-Fan
authors.initials: MF
authors.lastname: Cheng
authors.affiliation: Neural Regeneration Laboratory, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.affiliation: Department of Food Technology, Tajen University, Pingtung, Taiwan.
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chia
authors.affiliation: Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw.
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001688:Biological Products / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D005227:Fatty Acids / Q000494:pharmacology*; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008055:Lipids / Q000096:biosynthesis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001688:Biological Products; D005227:Fatty Acids; D008055:Lipids
keywords: Autophagy; Hepatic stellate cells; Liver fibrosis; Natural compounds; mTOR