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.

ERa-Dependent Regulation of Adropin Predicts Sex Differences in Liver Homeostasis during High-Fat Diet / C. Meda, A. Dolce, E. Vegeto, A. Maggi, S. Della Torre. - In: NUTRIENTS. - ISSN 2072-6643. - 14:16(2022 Aug 10), p. 3262.1. [10.3390/ nu14163262]

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

C. Meda
Co-primo
;
A. Dolce
Co-primo
;
E. Vegeto;A. Maggi
Penultimo
;
S. Della Torre
Ultimo
2022-08-10

Abstract

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.
liver; metabolism; NAFLD; high-fat diet; dietary lipids; hepatokines; adropin; sex and gender differences; estrogens; estrogen receptor alpha;
Settore BIO/10 - Biochimica
Settore BIO/14 - Farmacologia
CAR_RIC14AMAGG_CEND_M - A novel hypothesis on the development of metabolic syndrome in women - MAGGI, ADRIANA CATERINA - CAR_RIC - Bandi Fondazione Cariplo - 2014
https://www.mdpi.com/2072-6643/14/16/3262
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/935907
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