Etifoxine, a TSPO Ligand, Worsens Hepatitis C-Related Insulin Resistance but Relieves Lipid Accumulation

Yu Min Lin, Hung Yu Sun, Wen Tai Chiu, Hui Chen Su, Yu Chieh Chien, Heng Ai Chang, Lee Won Chong, Hung Chuen Chang, Kung Chia Young, Chyi Huey Bai, Chiung Wen Tsao

Research output: Contribution to journalArticle

Abstract

Etifoxine, an 18 kDa translocator protein (TSPO) agonist for the treatment of anxiety disorders in clinic, may be able to cause acute liver injury or cytolytic hepatitis. TSPO has been demonstrated to participate in inflammatory responses in infective diseases as well as to modulate glucose and lipid homeostasis. Hepatitis C virus (HCV) infection disrupts glucose and lipid homoeostasis, leading to insulin resistance (IR). Whether TSPO affects the HCV-induced IR remains unclear. Here, we found that the administration of etifoxine increased the TSPO protein expression and recovered the HCV-mediated lower mitochondrial membrane potential (MMP) without affecting HCV infection. Moreover, etifoxine reversed the HCV-induced lipid accumulation by modulating the expressions of sterol regulatory element-binding protein-1 and apolipoprotein J. On the other hand, in infected cells pretreated with etifoxine, the insulin-mediated insulin receptor substrate-1/Akt signals, forkhead box protein O1 translocation, and glucose uptake were blocked. Taken together, our results pointed out that etifoxine relieved the HCV-retarded MMP and reduced the lipid accumulation but deteriorated the HCV-induced IR by interfering with insulin signal molecules.

Original languageEnglish
Article number3102414
JournalBioMed Research International
Volume2019
DOIs
Publication statusPublished - Jan 1 2019

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Hepatitis C
Viruses
Hepacivirus
Insulin Resistance
Insulin
Ligands
Lipids
Proteins
Mitochondrial Membrane Potential
Virus Diseases
Glucose
Homeostasis
Clusterin
Sterol Regulatory Element Binding Protein 1
Forkhead Transcription Factors
Membranes
Insulin Receptor Substrate Proteins
Protein Transport
etifoxine
Anxiety Disorders

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Lin, Y. M., Sun, H. Y., Chiu, W. T., Su, H. C., Chien, Y. C., Chang, H. A., ... Tsao, C. W. (2019). Etifoxine, a TSPO Ligand, Worsens Hepatitis C-Related Insulin Resistance but Relieves Lipid Accumulation. BioMed Research International, 2019, [3102414]. https://doi.org/10.1155/2019/3102414

Etifoxine, a TSPO Ligand, Worsens Hepatitis C-Related Insulin Resistance but Relieves Lipid Accumulation. / Lin, Yu Min; Sun, Hung Yu; Chiu, Wen Tai; Su, Hui Chen; Chien, Yu Chieh; Chang, Heng Ai; Chong, Lee Won; Chang, Hung Chuen; Young, Kung Chia; Bai, Chyi Huey; Tsao, Chiung Wen.

In: BioMed Research International, Vol. 2019, 3102414, 01.01.2019.

Research output: Contribution to journalArticle

Lin, YM, Sun, HY, Chiu, WT, Su, HC, Chien, YC, Chang, HA, Chong, LW, Chang, HC, Young, KC, Bai, CH & Tsao, CW 2019, 'Etifoxine, a TSPO Ligand, Worsens Hepatitis C-Related Insulin Resistance but Relieves Lipid Accumulation', BioMed Research International, vol. 2019, 3102414. https://doi.org/10.1155/2019/3102414
Lin, Yu Min ; Sun, Hung Yu ; Chiu, Wen Tai ; Su, Hui Chen ; Chien, Yu Chieh ; Chang, Heng Ai ; Chong, Lee Won ; Chang, Hung Chuen ; Young, Kung Chia ; Bai, Chyi Huey ; Tsao, Chiung Wen. / Etifoxine, a TSPO Ligand, Worsens Hepatitis C-Related Insulin Resistance but Relieves Lipid Accumulation. In: BioMed Research International. 2019 ; Vol. 2019.
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