Therapeutic efficacy of 6-Gingerol and 6-Shogaol in promoting browning of white adipocytes vis-à-vis enhanced thermogenesis portrayed in high fat milieu

Ginger is a culinary spice, well documented for its inherent potent health beneficial effects, with Gingerols and Shogaols contributing as major bioactive constituents (23–25% and 18–25%) respectively. The present study aims to assess the therapeutic potential of 6-Gingerol (40 μM) and 6-Shogaol (40 μM) in promoting browning of white adipocytes vis-à-vis thermogenesis, tested in pre-adipocyte cell line (3T3-L1), and stromal vascular fraction (SVF)/obesogenic milieu derived from WNIN/Gr-Ob mutant rats. We investigated for anti-adipogenic potential of 6-Gingerol and 6-Shogaol (Oil-Red-O Staining), and evaluated for: (i) expression of brown specific markers like Ucp1, Pgc1α, Prdm16, Fgf21, Tmem26, Cidea and Pparγ, (ii) immunofluorescence for UCP-1, PGC-1α and PRDM16, (iii) thermogenesis using MitoTracker staining and (iv) oxygen consumption rate/OCR (assay kit). Further, we quantitated for beige progenitors/CD137+ve using flow cytometry, and measured multilocular vs unilocular adipocytes. To gain insights, molecular interactions of 6-Gingerol and 6-Shogaol with β3-adrenergic receptor membrane protein (β3-AR) were determined using in-silico docking studies. Our results demonstrate the potent efficacy of 6-Gingerol > 6-Shogaol as: (i) anti-adipogenic, (ii) enhanced formation of beige adipocytes (significant up-regulation of beige markers Fgf21, Tmem26 and Cidea, Ucp1, Prdm16, Pgc-1α, (iii) increased mitochondrial turnover, (iv) higher OCR, (v) induction of beige progenitors, (vi) preponderance of multilocular cells compared to unilocular cells, and (vii) better binding efficiency of 6-Gingerol > 6-Shogaol with β3-AR arrived from bond length and binding energy. Our present findings does advocate the promise(s) of Ginger, more so with 6-Gingerol as a potent therapeutic nutraceutical agent in obesity management.