17β-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30.
Senescence marker protein-30 (SMP30) plays an important role in intracellular Ca(2+) homeostasis. The aim of the present study was to investigate the effects of estrogens on liver apoptotic damage and changes in SMP30 expression induced by a high saturated fatty acid diet (HSFD). Ovariectomized mice (OVX) and sham-operated mice (SHAM) were randomly divided into five groups: SHAM fed a normal diet (SHAM/ND), SHAM fed HSFD (SHAM/HSFD), OVX fed ND (OVX/ND), OVX fed HSFD (OVX/HSFD) and OVX fed HSFD with 17β-estradiol (E2) supplementation using an implanted slow-release pellet (OVX/HSFD+E2). After 8 weeks, markers of endoplasmic reticulum (ER) stress and apoptosis, and levels of tumor necrosis factor-α (TNFα and SMP30 expression were investigated. Compared with SHAM/ND, OVX/HSFD mice showed significantly increased spliced X-box protein-1 (s-XBP1), phosphorylated eukaryotic initiation factor-2α (p-eIF2α), glucose-regulated protein 78 (GPR78), C/EBP homologous protein (CHOP), cytosolic cytochrome c, caspase-3 activity, and TNFα, and significantly decreased SMP30. These differences in OVX/HSFD mice were restored to the levels of SHAM/ND mice by E2 supplementation. These results suggest that E2 supplementation attenuates HSFD-induced liver apoptotic death in ovariectomized mice by up-regulating SMP30.
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan. michiaki@koto.kpu-m.ac.jp
Michiaki
M
Fukui
Takafumi
T
Senmaru
Goji
G
Hasegawa
Masahiro
M
Yamazaki
Mai
M
Asano
Yayoi
Y
Kagami
Akihito
A
Ishigami
Naoki
N
Maruyama
Koichi
K
Iwasa
Jo
J
Kitawaki
Yoshito
Y
Itoh
Takeshi
T
Okanoue
Mitsuhiro
M
Ohta
Hiroshi
H
Obayashi
Naoto
N
Nakamura
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004032:Diet / Q000009:adverse effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D004958:Estradiol / Q000008:administration & dosage*; D005227:Fatty Acids / Q000009:adverse effects*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation; D000071717:X-Box Binding Protein 1
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids; C000717248:Hspa5 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D000071701:Regulatory Factor X Transcription Factors; C513324:Rgn protein, mouse; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D004958:Estradiol; D053148:Caspase 3