Effect of hydroxylated polymethoxyflavones and acetylated polymethoxyflavones on adipogenesis in vivo and in vitro
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Tung, Yen-Chen.
Effect of hydroxylated polymethoxyflavones and acetylated polymethoxyflavones on adipogenesis in vivo and in vitro. Retrieved from
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TitleEffect of hydroxylated polymethoxyflavones and acetylated polymethoxyflavones on adipogenesis in vivo and in vitro
Date Created2015
Other Date2015-10 (degree)
Extent1 online resource (xii, 118 p. : ill.)
DescriptionExcess energy is a major cause of obesity and it can increase the number and size of adipocytes, eventually expanding the adipose tissue. Adipose tissue can be deposited in the intra-abdominal area and it affects the function of other organs, such as the liver, pancreas, and skeletal muscle, therefore, it is a risk factor related to liver disease and type 2 diabetes. Diet modification and the inhibition of the cause of obesity-related molecular mechanisms could be solutions for controlling the expansion of adipose mass and decreasing the prevalence of obesity. Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones (HPMFs) such as nobiletin, tangeretin, 5-demethyltangeretin, and 5-demethylnobiletin are unique flavonoids that almost exclusively exist in the peel of the citrus genus and have many health-beneficial effects. However, their lipophilic structure and characteristics give them poor aqueous solubility and low oral bioavailability. In the current research, we prepared 5-demethyltangeretin (5-OH-Tan), 5-demethylnobiletin (5-OH-Nob), 5-acetyloxy-6,7,8,4′-tetramethoxyflavone(5-Ac-Tan), and 5-acetyloxy-6,7,8,3′,4′-pentamethoxyflavone (5-Ac-Nob) through chemical modification from nobiletin and tangeretin. Firstly, we found that 5-Ac-Nob had better anti-adipogenesis activity than 5-OH-Nob, 5-OH-Tan, and its anti-adipogenesis ability by increased the phosphorylated-LKB1 and AMPKα protein levels and decreases the transcriptional factor SREBP-1 and lipogenesis-related enzyme fatty acid synthase protein levels in a 3T3-L1 preadipocyte model. Therefore, we further investigated the anti-adipogenesis effect of 5-Ac-Nob by using a diet with 45% calories from fat to induce obesity in C57BL/6J male mice. We found that mice fed with 5-Ac-Nob had lower body weight; intra-abdominal fat, plasma and liver triacylglycerol levels, and plasma cholesterol level and it had potential to prevent fatty liver by increased phosphorylated-LKB1 and AMPKα protein levels and increased the level of a lipogenesis-related enzyme, an inactive form of phosphorylated acetyl-CoA carboxylase protein, in the liver. In addition, we also found that 5-OH-Nob could be a metabolite hydrolyzed from 5-Ac-Nob in plasma when the mouse were administered with 100 mg/ kg bw of 5-Ac-Nob by oral gavage. All these results showed that 5-Ac-Nob could be a 5-OH-Nob prodrug to alleviate lipid accumulation by activated AMPKα and then affect lipid synthesis in vivo and in vitro.
NotePh.D.
NoteIncludes bibliographical references
Noteby Yen-Chen Tung
Genretheses, ETD doctoral
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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