2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone prevent progression of hyperglycemia and obesity via 5′-adenosine-monophosphate-activated protein kinase in diet-induced obese mice

Chi Ting Hsieh, Fang Rong Chang, Yi Hong Tsai, Yang-Chang Wu, Tusty Jiuan Hsieh

Research output: Contribution to journalArticle

Abstract

Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4′-methoxychalcone (compound 5) and 2-iodo-4′-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5′-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.

LanguageEnglish (US)
Article number2763
JournalInternational journal of molecular sciences
Volume19
Issue number9
DOIs
StatePublished - Sep 14 2018

Fingerprint

hyperglycemia
obesity
adenosine monophosphate
Obese Mice
diets
Adenosine Monophosphate
Nutrition
Medical problems
medicine
glucose
progressions
Hyperglycemia
Protein Kinases
mice
Obesity
disorders
Diet
proteins
Proteins
lead compounds

Keywords

  • Adipocyte
  • Chalcone
  • Flavonoid
  • Halogen
  • Skeletal muscle

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

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title = "2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone prevent progression of hyperglycemia and obesity via 5′-adenosine-monophosphate-activated protein kinase in diet-induced obese mice",
abstract = "Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4′-methoxychalcone (compound 5) and 2-iodo-4′-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5′-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.",
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T1 - 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone prevent progression of hyperglycemia and obesity via 5′-adenosine-monophosphate-activated protein kinase in diet-induced obese mice

AU - Hsieh, Chi Ting

AU - Chang, Fang Rong

AU - Tsai, Yi Hong

AU - Wu, Yang-Chang

AU - Hsieh, Tusty Jiuan

PY - 2018/9/14

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N2 - Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4′-methoxychalcone (compound 5) and 2-iodo-4′-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5′-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.

AB - Obesity and diabetes are global health-threatening issues. Interestingly, the mechanism of these pathologies is quite different among individuals. The discovery and development of new categories of medicines from diverse sources are urgently needed for preventing and treating diabetes and other metabolic disorders. Previously, we reported that chalcones are important for preventing biological disorders, such as diabetes. In this study, we demonstrate that the synthetic halogen-containing chalcone derivatives 2-bromo-4′-methoxychalcone (compound 5) and 2-iodo-4′-methoxychalcone (compound 6) can promote glucose consumption and inhibit cellular lipid accumulation via 5′-adenosine-monophosphate-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase 1 (ACC) phosphorylation in 3T3-L1 adipocytes and C2C12 skeletal myotubes. In addition, the two compounds significantly prevented body weight gain and impaired glucose tolerance, hyperinsulinemia, and insulin resistance, which collectively help to delay the progression of hyperglycemia in high-fat-diet-induced obese C57BL/6 mice. These findings indicate that 2-bromo-4′-methoxychalcone and 2-iodo-4′-methoxychalcone could act as AMPK activators, and may serve as lead compounds for a new class of medicines that target obesity and diabetes.

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