Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A

Tae Woo Jung, Byung Soo Youn, Hae Yoon Choi, So Young Lee, Ho Cheol Hong, Sae Jeong Yang, Hye-Jin Yoo, Baek-Hui Kim, Sei-Hyun Baik, Kyung Mook Choi

Research output: Contribution to journalArticle

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Abstract

Fetuin-A was recently identified as a novel hepatokine which is associated with obesity, insulin resistance and non-alcoholic fatty liver disease. Salsalate, a prodrug of salicylate with an anti-inflammatory effect and lower side effect profile, significantly lowers glucose and triglyceride levels, and increased adiponectin concentrations in randomized clinical trials. In this study, we examined the effects and regulatory mechanisms of salsalate and full length-adiponectin (fAd) on fetuin-A expression, steatosis and lipid metabolism in palmitate-treated HepG2 cells. Incubation of hepatocytes with palmitate significantly increased fetuin-A and SREBP-1c expression which lead to steatosis and knock-down of fetuin-A by siRNA restored these changes. Salsalate significantly down-regulated palmitate-induced fetuin-A mRNA expression and secretion in a dose- and time-dependent manner. Inhibition of palmitate-induced fetuin-A by salsalate was mediated by AMPK-mediated reduction of NFκB activity, which was blocked by AMPK siRNA or an inhibitor of AMPK. Salsalate attenuated the excessive steatosis by palmitate through SREBP-1c regulation in hepatocytes. Furthermore, fAd also showed suppression of palmitate-induced fetuin-A through the AMPK pathway and improvement of steatosis accompanied by restoration of SREBP-1c, PAPR-α and CD36. In preliminary in vivo experiments, salsalate treatment inhibited high fat diet (HFD)-induced steatosis as well as fetuin-A mRNA and protein expression in SD rats. In conclusion, salsalate and fAd improved palmitate-induced steatosis and impairment of lipid metabolism in hepatocytes via fetuin-A inhibition through the AMPK-NFκB pathway. AbbreviationsNAFLDnon-alcoholic fatty liver diseaseAMPKadenosine monophosphate-activated protein kinaseNF-κBnuclear factor-κBfAdfull- length adiponectinHFDhigh fat dietEMSAelectrophoretic mobility-shift assayChIPchromatin immunoprecipitation assay.

Original languageEnglish
Pages (from-to)960-969
Number of pages10
JournalBiochemical Pharmacology
Volume86
Issue number7
DOIs
Publication statusPublished - 2013 Aug 30

Fingerprint

alpha-2-HS-Glycoprotein
Adiponectin
Palmitates
AMP-Activated Protein Kinases
Liver
Sterol Regulatory Element Binding Protein 1
Hepatocytes
Lipid Metabolism
Small Interfering RNA
Fats
Alcoholic Fatty Liver
salicylsalicylic acid
Messenger RNA
Salicylates
Prodrugs
Hep G2 Cells
High Fat Diet
Nutrition
Immunoprecipitation
Restoration

Keywords

  • Adiponectin
  • AMPK
  • Fetuin-A
  • Hepatokine
  • NFκB
  • Non-alcoholic fatty liver disease
  • Salicylate
  • Salsalate

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A. / Jung, Tae Woo; Youn, Byung Soo; Choi, Hae Yoon; Lee, So Young; Hong, Ho Cheol; Yang, Sae Jeong; Yoo, Hye-Jin; Kim, Baek-Hui; Baik, Sei-Hyun; Choi, Kyung Mook.

In: Biochemical Pharmacology, Vol. 86, No. 7, 30.08.2013, p. 960-969.

Research output: Contribution to journalArticle

Jung, Tae Woo ; Youn, Byung Soo ; Choi, Hae Yoon ; Lee, So Young ; Hong, Ho Cheol ; Yang, Sae Jeong ; Yoo, Hye-Jin ; Kim, Baek-Hui ; Baik, Sei-Hyun ; Choi, Kyung Mook. / Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A. In: Biochemical Pharmacology. 2013 ; Vol. 86, No. 7. pp. 960-969.
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AU - Hong, Ho Cheol

AU - Yang, Sae Jeong

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