Endoplasmic reticulum stress in the livers of BDNF heterozygous knockout mice

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.