14 October 2019 : Laboratory Research
Berberine (BBR) Attenuated Palmitic Acid (PA)-Induced Lipotoxicity in Human HK-2 Cells by Promoting Peroxisome Proliferator-Activated Receptor α (PPAR-α)
Yueyue Wu1ABCDEFG, Fangyuan Chen1BC, Xinmei Huang1CDF, Rui Zhang1CDE, Zhiyan Yu1DEF, Zaoping Chen1EFG, Jun Liu1AG*DOI: 10.12659/MSM.916686
Med Sci Monit 2019; 25:7702-7708
Abstract
BACKGROUND: Berberine (BBR), a natural alkaloid isolated from Coptis chinensis, has frequently been reported as an antidiabetic reagent, partly due to its lipid-lowering activity. Evidence suggests that BBR ameliorates palmitate-induced lipid deposition and apoptosis in renal tubular epithelial cells (TECs), which tracks in tandem with the enhancement of peroxisome proliferator-activated receptor α (PPAR-α). The study aim was to investigate the roles of BBR in renal lipotoxicity in vitro, and investigate whether PPAR-α was the underlying mechanism.
MATERIAL AND METHODS: Human TECs (HK-2 cells) were injured with palmitic acid (PA), and then treated with BBR, BBR+PPAR-α inhibitor (GW6471), and PA+PPAR-α agonist (fenofibrate). Endoplasmic reticulum (ER) stress was assessed by measuring the expression of prospective evaluation of radial keratotomy (PERK), C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). Lipid metabolism was assessed by determining lipid anabolism-associated genes, including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and lipoprotein lipase (LPL), as well as lipid catabolism-associated gene, including carnitine palmitoyl transferase 1 (CPT1). Inflammatory response of HK-2 cells was evaluated by measuring interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Cell apoptosis and protein levels of cleaved-caspase-3 were evaluated.
RESULTS: PA downregulated PPAR-α and induced server lipotoxicity in HK-2 cells by ER stress, increasing lipid deposition, and elevating inflammatory response of HK-2 cells accompanied with inducting cell apoptosis and cleaved-caspase-3, which were obviously reversed by additional treatment of BBR or PPAR-α agonist. However, the protective effect of BBR in PA-induced lipotoxicity in HK-2 cells was significantly ameliorated by PPAR-α inhibitor.
CONCLUSIONS: BBR attenuated PA-induced lipotoxicity via the PPAR-α pathway.
Keywords: Lipid Regulating Agents, Medicine, Molecular Biology, Berberine, Cell Line, Endoplasmic Reticulum Chaperone BiP, Endoplasmic reticulum stress, PPAR alpha, Palmitic Acid
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