The dose-dependent pteryxin-mediated molecular mechanisms in suppressing adipogenesis in vitro. (July 2021)

• Record Type: Journal Article
• Authors: Nugara, Ruwani N.; Oku, Hirosuke; Saitoh, Seiko; Inafuku, Masashi; Iwasaki, Hironori; Kumara, R.P.; Undugoda, L.J.S.; Lankasena, B.N.S.
• Is Part Of: Journal of functional foods. Volume 82(2021)
• Publication Date: 2021-07
• Subjects: Adipogenesis -- Next generation sequencing -- Peucedanum japonicum Thunb -- Pteryxin -- Pyranocoumarin; ABCA1 ATP-binding cassette subfamily A, member 1 -- Aldh1a7 aldehyde dehydrogenase 1A7 -- AdipoQ adiponectin -- ACC acetyl-CoA carboxylase -- ADR Adrenaline -- AMPK 5′ adenosine monophosphate-activated protein kinase -- BCS bovine calf serum -- CA6 carbonic anhydrase 6 -- C/EBPα CCAAT/enhancer-binding protein alpha -- CMKLR1 chemerin chemokine like receptor 1 -- CPT1α carnitine palmitoyltransferase 1 alpha -- DEX dexamethasone -- DMEM dulbecco's modified eagle medium -- DUSP dual specificity phosphatase -- ECL enhanced luminol-based chemiluminescent -- ERK extracellular signal-regulated kinase -- FABP4 fatty acid binding protein 4 -- FAS fatty acid synthase -- FBS fetal bovine serum -- FDR false discovery rate -- FZD frizzled receptors -- GC-MS QP quadrupole gas chromatography mass spectrometer -- GLUT4 glucose transporter 4 -- 1H NMR proton nuclear magnetic resonance -- HPLC high performance liquid chromatography -- HSL/LIPE hormone-sensitive lipase -- IBMX 3-isobutyl-1-methylxanthine -- IGF1 insulin like growth factor 1 -- IRS insulin receptor substrate -- IPA ingenuity pathway analysis -- KL klotho protein encoding gene -- LPL lipoprotein lipase -- MEST paternally expressed gene 1/mesoderm specific transcript -- MTS 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium -- NGS next generation sequencing -- p-AMPK phosphorylated 5′AMP-activated protein kinase -- PBS phosphate buffer solution -- p-ERK phosphorylated extracellular signal-regulated kinase -- p-p38 MAPK phosphorylated p38 mitogen-activated protein kinase -- p38 MAPK p38 mitogen-activated protein kinase -- PGC1α peroxisome proliferator-activated receptor gamma coactivator 1 alpha -- PJT Peucedanum japonicum Thunb -- PFKB phosphofructo-2-kinase/fructose-2, 6-bis-phosphate -- PI3K phosphoinositide-3-kinase -- PPARγ peroxisome proliferator-activated receptor gamma -- PREF1 Preadipocyte factor 1 -- PTX20 pteryxin 20 µg/mL -- PTX50 pteryxin 50 µg/mL -- PVDF polyvinylidene difluoride -- SIRT-1 sirtuin-1 -- SREBP1c sterol regulatory element-binding protein-1c -- TG triglyceride -- TGF-β transforming growth factor-β -- TP63 tumor protein 63 -- UCP uncoupling protein -- Wnt Wnt family member; Functional foods -- Analysis -- Periodicals; Food -- Biotechnology -- Periodicals; Nutrition -- Periodicals; 613.2
• DOI: 10.1016/j.jff.2021.104508
• Languages: English
• ISSNs: 1756-4646

Abstract

Graphical abstract: Highlights: Pteryxin follow a dual mechanism to attenuate adipogenesis. Suppression of early or late adipogenesis decided by the pteryxin dose. PTX₂₀ regulated ERK1/2 signaling followed by acceleration in lipolysis. PTX₅₀ regulated AMPK pathway and carbohydrate metabolism to reduce obesity. Abstract: The aim was to perform an in-depth characterization of pteryxin in the anti-obesity related molecular mechanisms using 3T3-L1 preadipocytes. Cells were treated with pteryxin 20 (PTX20 ) or 50 (PTX50 ) μg/mL during cell differentiation or maintenance period. Pteryxin dose-dependently suppressed adipogenic gene network. PTX20 downregulated key lipogenic genes suppressing fatty acid synthesis allotting the anti-adipogenesis in the late adipocyte formation stage. PTX50 downregulated adipogenesis related genes, and accelerated lipolytic activity by repressing the adipocyte size marker gene, MEST. In addition to Wnt5a, PTX50 suppressed adipocyte differentiation through TGF-β/Smad3 signaling pathway with the maximum adiposity inhibition in the early stage of adipogenesis and regulated the carbohydrate metabolism. Pteryxin regulated phosphorylation of ERK1/2 and AMPK, and decreased p38 MAPK to repress the mature adipocyte formation. Overall, we have demonstrated the anti-adipogenic characteristics of pteryxin consistent to its dose. PTX50 may serve as a potential candidate to ameliorate adiposity and improve the carbohydrate metabolism.