Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice.
Adropin
Estrogen
Fatty Liver
Menopause
OVX
Transcriptome
Journal
Molecular metabolism
ISSN: 2212-8778
Titre abrégé: Mol Metab
Pays: Germany
ID NLM: 101605730
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
24
02
2022
revised:
13
03
2022
accepted:
24
03
2022
pubmed:
2
4
2022
medline:
11
5
2022
entrez:
1
4
2022
Statut:
ppublish
Résumé
Menopause is associated with visceral adiposity, hepatic steatosis and increased risk for cardiovascular disease. As estrogen replacement therapy is not suitable for all postmenopausal women, a need for alternative therapeutics and biomarkers has emerged. 9-week-old C57BL/6 J female mice were subjected to ovariectomy (OVX) or SHAM surgery (n = 10 per group), fed a standard diet and sacrificed 6- & 12 weeks post-surgery. Increased weight gain, hepatic triglyceride content and changes in hepatic gene expression of Cyp17a1, Rgs16, Fitm1 as well as Il18, Rares2, Retn, Rbp4 in mesenteric visceral adipose tissue (VAT) were observed in OVX vs. SHAM. Liver RNA-sequencing 6-weeks post-surgery revealed changes in genes and microRNAs involved in fat metabolism in OVX vs. SHAM mice. Energy Homeostasis Associated gene (Enho) coding for the hepatokine adropin was significantly reduced in OVX mice livers and strongly inversely correlated with weight gain (r = -0.7 p < 0.001) and liver triglyceride content (r = -0.4, p = 0.04), with a similar trend for serum adropin. In vitro, Enho expression was tripled by 17β-estradiol in BNL 1 ME liver cells with increased adropin in supernatant. Analysis of open-access datasets revealed increased hepatic Enho expression in estrogen treated OVX mice and estrogen dependent ERα binding to Enho. Treatment of 5-month-old OVX mice with Adropin (i.p. 450 nmol/kg/twice daily, n = 4,5 per group) for 6-weeks reversed adverse adipokine gene expression signature in VAT, with a trended increase in lean body mass and decreased liver TG content with upregulation of Rgs16. OVX is sufficient to induce deranged metabolism in adult female mice. Hepatic adropin is regulated by estrogen, negatively correlated with adverse OVX-induced metabolic phenotypes, which were partially reversed with adropin treatment. Adropin should be further explored as a potential therapeutic target and biomarker for menopause-related metabolic derangement.
Identifiants
pubmed: 35364299
pii: S2212-8778(22)00051-5
doi: 10.1016/j.molmet.2022.101482
pmc: PMC9044006
pii:
doi:
Substances chimiques
Enho protein, human
0
Estrogens
0
Intercellular Signaling Peptides and Proteins
0
RBP4 protein, human
0
Retinol-Binding Proteins, Plasma
0
Triglycerides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
101482Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.
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