Zingiber officinale Leaf Subcritical Water Extract Suppresses Adipogenesis and Lipogenesis in 3T3-L1 Adipocytes via the AMPK-SREBP-1c Signaling Pathway.

Zingiber officinale, commonly known as ginger, has long been utilized as a medicinal plant due to its diverse pharmacological properties. However, research has predominantly focused on the rhizome, while the leaf is frequently regarded as a byproduct. In this study, we investigated the functional relevance of the ginger leaf, concentrating on the anti-obesity effects of ginger leaf subcritical water extract (GLE) and the underlying mechanisms in 3T3-L1 adipocytes. GLE reduced lipid accumulation in a concentration-dependent manner on day 7 of differentiation and suppressed the expression of adipogenesis-associated factors, including CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ, fatty acid binding protein 4, and lipoprotein lipase on both days 2 and 7. GLE also modulated early adipogenesis by inhibiting p38 phosphorylation and downregulating C/EBPβ expression at 4 h of differentiation. Additionally, GLE decreased the expression of acetyl-CoA carboxylase, fatty acid synthase, and stearoyl-CoA desaturase 1-key enzymes involved in lipogenesis-from the early stages of adipocyte differentiation. Furthermore, GLE directly phosphorylated adenosine monophosphate-activated protein kinase (AMPK), leading to inhibition of the expression of sterol regulatory element-binding protein-1c (SREBP-1c), an upstream regulator of both adipogenesis and lipogenesis. In summary, GLE exerted anti-obesity effects in 3T3-L1 adipocytes by inhibiting the transcriptional activation of adipogenic and lipogenic regulators during the early stage of differentiation, and maintaining their downregulation at later stages, and it was found to be mediated by the AMPK-SREBP-1c signaling pathway.