1 research outputs found
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
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