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

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• 作者：Yen-Chen Tung ; Shiming Li ; Qingrong Huang ; Wei-Lun Hung ; Chi-Tang Ho ; Guor-Jien Wei ; Min-Hsiung Pan
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2016
• 出版时间：April 27, 2016
• 年：2016
• 卷：64
• 期：16
• 页码：3196-3205
• 全文大小：560K
• 年卷期：0
• ISSN：1520-5118

文摘

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.