ERα-Dependent Regulation of Adropin Predicts Sex Differences in Liver Homeostasis during High-Fat Diet

Non-alcoholic fatty liver disease (NAFLD) represents a public health issue, due to its prevalence and association with other cardiometabolic diseases. Growing evidence suggests that NAFLD alters the production of hepatokines, which, in turn, influence several metabolic processes. Despite accumulatin...

Full description

Saved in:
Bibliographic Details
Published in:Nutrients 2022-08, Vol.14 (16), p.3262
Main Authors: Meda, Clara, Dolce, Arianna, Vegeto, Elisabetta, Maggi, Adriana, Della Torre, Sara
Format: Article
Language:English
Subjects:
Antibiotics
Data analysis
Diet
dietary lipids
Estrogen
Estrogen receptors
Estrogens
Experiments
Fatty liver
Females
Gender differences
Gene expression
Health aspects
hepatokines
High fat diet
Homeostasis
In vivo methods and tests
Lipids
Liver
Liver diseases
Males
Metabolic disorders
metabolism
NAFLD
Pathogenesis
Peptide hormones
Phenols
Physiological aspects
Prevention
Public health
Receptors
Risk factors
Sex differences
Sex factors in disease
Sexes
Sexual dimorphism
Software
Vagina
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Non-alcoholic fatty liver disease (NAFLD) represents a public health issue, due to its prevalence and association with other cardiometabolic diseases. Growing evidence suggests that NAFLD alters the production of hepatokines, which, in turn, influence several metabolic processes. Despite accumulating evidence on the major role of estrogen signaling in the sexually dimorphic nature of NAFLD, dependency of hepatokine expression on sex and estrogens has been poorly investigated. Through in vitro and in vivo analysis, we determined the extent to which hepatokines, known to be altered in NAFLD, can be regulated, in a sex-specific fashion, under different hormonal and nutritional conditions. Our study identified four hepatokines that better recapitulate sex and estrogen dependency. Among them, adropin resulted as one that displays a sex-specific and estrogen receptor alpha (ERα)-dependent regulation in the liver of mice under an excess of dietary lipids (high-fat diet, HFD). Under HFD conditions, the hepatic induction of adropin negatively correlates with the expression of lipogenic genes and with fatty liver in female mice, an effect that depends upon hepatic ERα. Our findings support the idea that ERα-mediated induction of adropin might represent a potential approach to limit or prevent NAFLD.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu14163262