6-Gingerol, a functional polyphenol of ginger, promotes browning through an AMPK-dependent pathway in 3T3-L1 adipocytes.

The main purpose of the present study was to investigate the browning effects of 6-gingerol (6G), one of the main functional compounds in an ethyl acetate extract of ginger (ginger ethyl acetate fraction, GEF), and its underlying mechanisms. In this study, we first discovered that GEF stimulated brown adipocyte differentiation by upregulating the expression levels of browning-specific transcription makers (UCP1, PRDM16 and PGC-1α), thereby reducing lipid metabolism transcriptional regulator (C/EBPα) expression in 3T3-L1 differentiated adipocytes. Then, 6G (47.81 ± 0.62 mg/g) was identified as one of the main functional compounds in GEF using high-performance liquid chromatography (HPLC). 6G promoted adipocyte browning, as evidenced by increases in some brown/beige fat-specific genes (PGC-1α, Cidea, Prdm16, Cited1, SIRT1, Tmem26 and Ucp1) and protein (UCP1, CEBP/β, PGC-1α and PRDM16) expression levels. Moreover, 6G greatly improved mitochondrial respiration and energy metabolism by upregulating the expression levels of some mitochondrial biogenesis markers (Tfam, Nrf1, SIRT1 and p-AMPK/AMPK) and increasing the uncoupled oxygen consumption rate (OCR) of protons leaked in 3T3-L1 cells. Comparison of the experimental results obtained with an inhibitor (dorsomorphin) and an activator (5-aminoimidazole-4-carboxamide ribonucleotide, AICAR) suggested that the 6G-associated regulation of energy metabolism effect was mediated partly through the AMPK signaling pathway. This study provides new insight into the promotion of fat browning and lipid metabolism regulation by 6G and thus suggests that 6G likely has potential therapeutic effects on obesity.