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

Yen Chen Tung, Shiming Li, Qingrong Huang, Wei Lun Hung, Chi Tang Ho, Guor Jien Wei, Min Hsiung Pan

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3196-3205
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Volume64
Issue number16
DOIs
Publication statusPublished - Apr 27 2016
Externally publishedYes

Fingerprint

AMP-activated protein kinase
High Fat Diet
Adenosine Monophosphate
high fat diet
Nutrition
Inbred C57BL Mouse
Adenosine
Protein Kinases
bioavailability
Fats
triacylglycerols
citrus peels
Lipids
water solubility
mice
lipogenesis
abdominal fat
lipids
mouth
flavonoids

Keywords

  • 3T3-L1 preadipocytes
  • 5-acetyloxy-6,7,8,3′,4′-pentamethoxyflavone
  • high-fat diet
  • LKB1-AMPK pathway

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

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.

In: Journal of Agricultural and Food Chemistry, Vol. 64, No. 16, 27.04.2016, p. 3196-3205.

Research output: Contribution to journalArticle

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abstract = "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.",
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T1 - 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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AU - Ho, Chi Tang

AU - Wei, Guor Jien

AU - Pan, Min Hsiung

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N2 - 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.

AB - 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.

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