Abstract

Background: Currently, more than one-third of the global population is overweight or obese, which is a risk factor for major causes of death including cardiovascular disease, numerous cancers, and diabetes. Kinsenoside, a major active component of Anoectochilus formosanus exhibits antihyperglycemic, antihyperliposis, and hepatoprotective effects and can be used to prevent and manage obesity. Purpose: This study examined the catabolic effects of kinsenoside on lipolysis in adipocytes transformed from C3H10T1/2 cells. Study design/methods: The lipolytic effect of kinsenoside in C3H10T1/2 adipocytes was evaluated by oil-red O staining and glycerol production. The underlying mechanisms were assessed by Western blots, chromatin immunoprecipitation (IP), Co-IP, EMSA and siRNAs verification. Results: We demonstrated that kinsenoside increased both adipose triglyceride lipase (ATGL)-mediated lipolysis, which was upregulated by AMP-activated protein kinase (AMPK) activation, and the hydrolysis of triglycerides to glycerol and fatty acids that require transportation into mitochondria for further β-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferator-activated receptor alpha (PPARα) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1α, facilitating AMPK-mediated PGC-1α phosphorylation and increasing the interaction of PPARα with its coactivator, PGC-1α. This interaction elevated the expression of CPT1, a shuttle for the mitochondrial transport of fatty acids, in kinsenoside-treated cells. In addition, AMPK-phosphorylation-mediated CREB activation caused kinsenoside-mediated PGC-1α upregulation. Conclusion: AMPK activation not only elevated ATGL expression for lipolysis but also induced CPT1 expression for further mitochondrial translocation of fatty acids. The results suggested that the mechanism underlying the catabolic effects of kinsenoside on lipolysis and increased CPT1 induction was mediated through an AMPK-dependent pathway.

Original languageEnglish
Pages (from-to)641-647
Number of pages7
JournalPhytomedicine
Volume22
Issue number6
DOIs
Publication statusPublished - May 10 2015

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PPAR alpha
AMP-Activated Protein Kinases
Lipolysis
Adipocytes
Fatty Acids
Phosphorylation
Lipase
Glycerol
Carrier Proteins
Carnitine O-Palmitoyltransferase
3-glucopyranosyloxybutanolide
Chromatin Immunoprecipitation
Immunoprecipitation
Hypoglycemic Agents
Cause of Death
Mitochondria
Triglycerides
Hydrolysis
Cardiovascular Diseases
Up-Regulation

Keywords

  • AMP-activated protein kinase
  • Anoectochilus formosanus
  • C3H10T1/2 cells
  • Kinsenoside
  • Lipolysis

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Complementary and alternative medicine
  • Molecular Medicine
  • Medicine(all)

Cite this

@article{7a5712ee44094d07aabc562318c29c75,
title = "Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes: Roles of AMPK and PPARα in the lipolytic effect of kinsenoside",
abstract = "Background: Currently, more than one-third of the global population is overweight or obese, which is a risk factor for major causes of death including cardiovascular disease, numerous cancers, and diabetes. Kinsenoside, a major active component of Anoectochilus formosanus exhibits antihyperglycemic, antihyperliposis, and hepatoprotective effects and can be used to prevent and manage obesity. Purpose: This study examined the catabolic effects of kinsenoside on lipolysis in adipocytes transformed from C3H10T1/2 cells. Study design/methods: The lipolytic effect of kinsenoside in C3H10T1/2 adipocytes was evaluated by oil-red O staining and glycerol production. The underlying mechanisms were assessed by Western blots, chromatin immunoprecipitation (IP), Co-IP, EMSA and siRNAs verification. Results: We demonstrated that kinsenoside increased both adipose triglyceride lipase (ATGL)-mediated lipolysis, which was upregulated by AMP-activated protein kinase (AMPK) activation, and the hydrolysis of triglycerides to glycerol and fatty acids that require transportation into mitochondria for further β-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferator-activated receptor alpha (PPARα) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1α, facilitating AMPK-mediated PGC-1α phosphorylation and increasing the interaction of PPARα with its coactivator, PGC-1α. This interaction elevated the expression of CPT1, a shuttle for the mitochondrial transport of fatty acids, in kinsenoside-treated cells. In addition, AMPK-phosphorylation-mediated CREB activation caused kinsenoside-mediated PGC-1α upregulation. Conclusion: AMPK activation not only elevated ATGL expression for lipolysis but also induced CPT1 expression for further mitochondrial translocation of fatty acids. The results suggested that the mechanism underlying the catabolic effects of kinsenoside on lipolysis and increased CPT1 induction was mediated through an AMPK-dependent pathway.",
keywords = "AMP-activated protein kinase, Anoectochilus formosanus, C3H10T1/2 cells, Kinsenoside, Lipolysis",
author = "Cheng, {Kur Ta} and Wang, {Yu Shiou} and Chou, {Hsiu Chu} and Chih-Cheng Chang and Lee, {Ching Kuo} and Juan, {Shu Hui}",
year = "2015",
month = "5",
day = "10",
doi = "10.1016/j.phymed.2015.04.001",
language = "English",
volume = "22",
pages = "641--647",
journal = "Phytomedicine",
issn = "0944-7113",
publisher = "Urban und Fischer Verlag Jena",
number = "6",

}

TY - JOUR

T1 - Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes

T2 - Roles of AMPK and PPARα in the lipolytic effect of kinsenoside

AU - Cheng, Kur Ta

AU - Wang, Yu Shiou

AU - Chou, Hsiu Chu

AU - Chang, Chih-Cheng

AU - Lee, Ching Kuo

AU - Juan, Shu Hui

PY - 2015/5/10

Y1 - 2015/5/10

N2 - Background: Currently, more than one-third of the global population is overweight or obese, which is a risk factor for major causes of death including cardiovascular disease, numerous cancers, and diabetes. Kinsenoside, a major active component of Anoectochilus formosanus exhibits antihyperglycemic, antihyperliposis, and hepatoprotective effects and can be used to prevent and manage obesity. Purpose: This study examined the catabolic effects of kinsenoside on lipolysis in adipocytes transformed from C3H10T1/2 cells. Study design/methods: The lipolytic effect of kinsenoside in C3H10T1/2 adipocytes was evaluated by oil-red O staining and glycerol production. The underlying mechanisms were assessed by Western blots, chromatin immunoprecipitation (IP), Co-IP, EMSA and siRNAs verification. Results: We demonstrated that kinsenoside increased both adipose triglyceride lipase (ATGL)-mediated lipolysis, which was upregulated by AMP-activated protein kinase (AMPK) activation, and the hydrolysis of triglycerides to glycerol and fatty acids that require transportation into mitochondria for further β-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferator-activated receptor alpha (PPARα) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1α, facilitating AMPK-mediated PGC-1α phosphorylation and increasing the interaction of PPARα with its coactivator, PGC-1α. This interaction elevated the expression of CPT1, a shuttle for the mitochondrial transport of fatty acids, in kinsenoside-treated cells. In addition, AMPK-phosphorylation-mediated CREB activation caused kinsenoside-mediated PGC-1α upregulation. Conclusion: AMPK activation not only elevated ATGL expression for lipolysis but also induced CPT1 expression for further mitochondrial translocation of fatty acids. The results suggested that the mechanism underlying the catabolic effects of kinsenoside on lipolysis and increased CPT1 induction was mediated through an AMPK-dependent pathway.

AB - Background: Currently, more than one-third of the global population is overweight or obese, which is a risk factor for major causes of death including cardiovascular disease, numerous cancers, and diabetes. Kinsenoside, a major active component of Anoectochilus formosanus exhibits antihyperglycemic, antihyperliposis, and hepatoprotective effects and can be used to prevent and manage obesity. Purpose: This study examined the catabolic effects of kinsenoside on lipolysis in adipocytes transformed from C3H10T1/2 cells. Study design/methods: The lipolytic effect of kinsenoside in C3H10T1/2 adipocytes was evaluated by oil-red O staining and glycerol production. The underlying mechanisms were assessed by Western blots, chromatin immunoprecipitation (IP), Co-IP, EMSA and siRNAs verification. Results: We demonstrated that kinsenoside increased both adipose triglyceride lipase (ATGL)-mediated lipolysis, which was upregulated by AMP-activated protein kinase (AMPK) activation, and the hydrolysis of triglycerides to glycerol and fatty acids that require transportation into mitochondria for further β-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferator-activated receptor alpha (PPARα) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1α, facilitating AMPK-mediated PGC-1α phosphorylation and increasing the interaction of PPARα with its coactivator, PGC-1α. This interaction elevated the expression of CPT1, a shuttle for the mitochondrial transport of fatty acids, in kinsenoside-treated cells. In addition, AMPK-phosphorylation-mediated CREB activation caused kinsenoside-mediated PGC-1α upregulation. Conclusion: AMPK activation not only elevated ATGL expression for lipolysis but also induced CPT1 expression for further mitochondrial translocation of fatty acids. The results suggested that the mechanism underlying the catabolic effects of kinsenoside on lipolysis and increased CPT1 induction was mediated through an AMPK-dependent pathway.

KW - AMP-activated protein kinase

KW - Anoectochilus formosanus

KW - C3H10T1/2 cells

KW - Kinsenoside

KW - Lipolysis

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U2 - 10.1016/j.phymed.2015.04.001

DO - 10.1016/j.phymed.2015.04.001

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C2 - 26055129

AN - SCOPUS:84929087798

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