Naringenin attenuates hepatitis B virus X protein-induced hepatic steatosis

BMC Complement Altern Med. 2017 Nov 28;17(1):505. doi: 10.1186/s12906-017-2019-2.

Abstract

Background: Naringenin (Nar), a common dietary flavonoid abundantly present in fruits, vegetables, and Chinese herbs, is believed to possess strong anti-inflammatory properties and to modulate hepatic apolipoprotein and lipid synthesis. However, there are no reports describing Nar's effects on the hepatitis B virus protein X (HBx) -induced hepatic steatosis, and the detailed molecular mechanisms of the compound's effects are still unclear.

Methods: Nar was administered by oral gavage to HBx-transgenic mice from 4 to 6 weeks of age. Mice were sacrificed after 14 days of once-daily naringenin administration. Liver tissues and sera were collected for histopathology and biochemical analysis.

Results: Nar counteracted hepatic lipid accumulation and liver dysfunction in HBx-transgenic mice. In addition, Nar significantly decreased expression of adipogenic and lipogenic genes in mice, suggesting that the compound may have therapeutic effects in the early stages of HBx-mediated hepatic steatosis. These results indicated that naringenin inhibits HBx-induced expression of hepatic adipogenic and lipogenic genes through suppression of HBx-induced gene expression, including decreases in the transcriptional activity of SREBP1c, LXRα, and PPARγ in HBx-trangenic mice and HBx-transfected HepG2 cells.

Conclusions: Results from this study suggested that Nar may serve as a therapeutic agent for preventing HBx-infected hepatic steatosis in humans.

Keywords: Adiponectin; CD36; FAS; HBx; Hepatic steatosis; LXRα; Naringenin; PPARγ; SREBP1c; aP2.

MeSH terms

  • Animals
  • Fatty Liver / metabolism*
  • Fatty Liver / pathology
  • Flavanones / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Transgenic
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins

Substances

  • Flavanones
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • naringenin