Endoplasmic reticulum stress in the livers of BDNF heterozygous knockout mice

CıRRıK S., HACIOGLU G., Abidin İ., Aydın-Abidin S., NOYAN T.

ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY, vol.125, no.4, pp.378-386, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 125 Issue: 4
  • Publication Date: 2019
  • Doi Number: 10.1080/13813455.2018.1489850
  • Journal Name: ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.378-386
  • Keywords: BDNF heterozygous knockout mice, endoplasmic reticulum stress, apoptosis, steatosis, SREBP-1c, UNFOLDED PROTEIN RESPONSE, NEUROTROPHIC FACTOR BDNF, HEPATIC STEATOSIS, ER STRESS, INSULIN-RESISTANCE, LIPID-METABOLISM, EXPRESSION, ALPHA, DEATH, CHOP
  • Karadeniz Technical University Affiliated: Yes

Abstract

Context: Involvement of endoplasmic reticulum (ER) stress and brain-derived neurotrophic factor (BDNF) in hepatic lipid metabolism has been reported previously. Objective: The effects of chronic BDNF deficiency on ER stress response in the livers were examined in this study. Methods: BDNF(+/-) mice, characterised by BDNF deficiency, and their wild-type (WT) littermates were used. The ER stress was induced by tunicamycin (Tm) (0.5 mg/kg, intraperitoneal). Animals were divided into four groups; WT, WT + Tm, BDNF(+/-), and BDNF(+/-)+Tm. Results: At the basal conditions, BDNF deficiency did not affect hepatic cell death or lipid accumulation. However, during ER stress, BDNF(+/-)+Tm group showed increased apoptosis, GADD153 immunostaining, sterol regulatory element-binding protein-1c (SREBP-1c) level, and steatosis compared to the WT + Tm group. Conclusion: Endogenous BDNF might be protective against apoptosis through GADD153 suppression and steatosis via SREBP-1c suppression during ER stress. This effect of BDNF might be clinically important for type 2 diabetes and obesity, which are related with both ER stress and BDNF deficiency.