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5-Demethylnobiletin and 5-Acetoxy-6,7,8,3′,4′-pentamethoxyflavone Suppress Lipid Accumulation by Activating the LKB1-AMPK Pathway in 3T3-L1 Preadipocytes and High Fat Diet-Fed C57BL/6 Mice
- Tung, Yen-Chen, Li, Shiming, Huang, Qingrong, Hung, Wei-Lun, Ho, Chi-Tang, Wei, Guor-Jien, Pan, Min-Hsiung
- Journal of agricultural and food chemistry 2016 v.64 no.16 pp. 3196-3205
- adenosine, adipogenesis, bioavailability, body weight, cholesterol, citrus peels, enzymes, liver, males, mice, oral administration, polymethoxyflavones, solubility, transcription factors, triacylglycerols
- Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones (HPMFs), such as nobiletin (Nob) and 5-demethylnobiletin (5-OH-Nob), are unique flavonoids that are found exclusively in citrus peels. Nobiletin has been shown to suppress adipogenesis in vitro, but the antiadipogenic activity of 5-OH-Nob has not been investigated. Both nobiletin and 5-OH-Nob have poor aqueous solubility and low oral bioavailability. We employed chemical modification to produce the acetyl derivative of 5-OH-Nob, that is, 5-acetyloxy-6,7,8,3′,4′-pentamethoxyflavone (5-Ac-Nob), to improve its bioavailability and bioactive efficiency. We found that 5-Ac-Nob reduced triacylglycerol (TG) content to a greater extent than 5-OH-Nob in 3T3-L1 preadipocytes. Orally administered 5-Ac-Nob resulted in a significant reduction in body weight, intra-abdominal fat, plasma and liver TG levels, and plasma cholesterol level in high fat diet-induced obese male C57BL/6J mice. The 5-Ac-Nob treatment decreased lipid accumulation by triggering the adenosine 5′-monophosphate-activated protein kinase (AMPK) pathway to alter transcriptional factors or lipogenesis-related enzymes in vivo and in vitro.