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Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease

Lipodystrophy (LD) indicates a group of rare disorders, with generalized or partial loss of white adipose tissue (WAT) often associated with metabolic derangements. Heterogeneity/wide spectrum of the disease and lack of biomarkers make diagnosis often difficult. MicroRNAs are important to maintain a...

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Autores principales: Dattilo, Alessia, Ceccarini, Giovanni, Scabia, Gaia, Magno, Silvia, Quintino, Lara, Pelosini, Caterina, Salvetti, Guido, Cusano, Roberto, Massidda, Matteo, Montanelli, Lucia, Gilio, Donatella, Gatti, Gianluca, Giacomina, Alessandro, Costa, Mario, Santini, Ferruccio, Maffei, Margherita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207177/
https://www.ncbi.nlm.nih.gov/pubmed/35733784
http://dx.doi.org/10.3389/fendo.2022.866679
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author Dattilo, Alessia
Ceccarini, Giovanni
Scabia, Gaia
Magno, Silvia
Quintino, Lara
Pelosini, Caterina
Salvetti, Guido
Cusano, Roberto
Massidda, Matteo
Montanelli, Lucia
Gilio, Donatella
Gatti, Gianluca
Giacomina, Alessandro
Costa, Mario
Santini, Ferruccio
Maffei, Margherita
author_facet Dattilo, Alessia
Ceccarini, Giovanni
Scabia, Gaia
Magno, Silvia
Quintino, Lara
Pelosini, Caterina
Salvetti, Guido
Cusano, Roberto
Massidda, Matteo
Montanelli, Lucia
Gilio, Donatella
Gatti, Gianluca
Giacomina, Alessandro
Costa, Mario
Santini, Ferruccio
Maffei, Margherita
author_sort Dattilo, Alessia
collection PubMed
description Lipodystrophy (LD) indicates a group of rare disorders, with generalized or partial loss of white adipose tissue (WAT) often associated with metabolic derangements. Heterogeneity/wide spectrum of the disease and lack of biomarkers make diagnosis often difficult. MicroRNAs are important to maintain a correct WAT function and WAT is a source of circulating miRNAs (cmiRs). miRNAs from 320 family were previously detected in the WAT and variably associated to the metabolic syndrome. Our aim was then to investigate if LD can result in altered abundance of cmiRs-320. We collected samples from a cohort of LD subjects of various subtypes and from age matched controls. Use of quantitative PCR determined that cmiRs- 320a-3p, 320b, 320c, 320e are upregulated, while 320d is downregulated in LD. CmiRs-320 power as classifiers was more powerful in the most extreme and defined forms of LD, including the generalized and the Dunnigan subtypes. cmiR-320a-3p showed significant inverse relationships with plasma leptin (P < 0.0001), typically low in LD. The hepatic enzymes gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the marker of inflammation C-reactive protein (CRP) were inversely related to cmiR 320d (P < 0.05, for CRP and GGT; P < 0.01, for AST and ALT). Gene ontology analysis revealed cell-cell adhesion as a process regulated by 320 miRNAs targets, thus disclosing a novel route to investigate origin of WAT loss/dysfunction. In conclusion, cmiRs-320 constitute novel biomarkers of LD, abundance of miR320a-3p is inversely associated to indicators related to WAT function, while downregulation of cmiR-320d predicts an altered hepatic profile and higher inflammation.
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spelling pubmed-92071772022-06-21 Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease Dattilo, Alessia Ceccarini, Giovanni Scabia, Gaia Magno, Silvia Quintino, Lara Pelosini, Caterina Salvetti, Guido Cusano, Roberto Massidda, Matteo Montanelli, Lucia Gilio, Donatella Gatti, Gianluca Giacomina, Alessandro Costa, Mario Santini, Ferruccio Maffei, Margherita Front Endocrinol (Lausanne) Endocrinology Lipodystrophy (LD) indicates a group of rare disorders, with generalized or partial loss of white adipose tissue (WAT) often associated with metabolic derangements. Heterogeneity/wide spectrum of the disease and lack of biomarkers make diagnosis often difficult. MicroRNAs are important to maintain a correct WAT function and WAT is a source of circulating miRNAs (cmiRs). miRNAs from 320 family were previously detected in the WAT and variably associated to the metabolic syndrome. Our aim was then to investigate if LD can result in altered abundance of cmiRs-320. We collected samples from a cohort of LD subjects of various subtypes and from age matched controls. Use of quantitative PCR determined that cmiRs- 320a-3p, 320b, 320c, 320e are upregulated, while 320d is downregulated in LD. CmiRs-320 power as classifiers was more powerful in the most extreme and defined forms of LD, including the generalized and the Dunnigan subtypes. cmiR-320a-3p showed significant inverse relationships with plasma leptin (P < 0.0001), typically low in LD. The hepatic enzymes gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and the marker of inflammation C-reactive protein (CRP) were inversely related to cmiR 320d (P < 0.05, for CRP and GGT; P < 0.01, for AST and ALT). Gene ontology analysis revealed cell-cell adhesion as a process regulated by 320 miRNAs targets, thus disclosing a novel route to investigate origin of WAT loss/dysfunction. In conclusion, cmiRs-320 constitute novel biomarkers of LD, abundance of miR320a-3p is inversely associated to indicators related to WAT function, while downregulation of cmiR-320d predicts an altered hepatic profile and higher inflammation. Frontiers Media S.A. 2022-06-06 /pmc/articles/PMC9207177/ /pubmed/35733784 http://dx.doi.org/10.3389/fendo.2022.866679 Text en Copyright © 2022 Dattilo, Ceccarini, Scabia, Magno, Quintino, Pelosini, Salvetti, Cusano, Massidda, Montanelli, Gilio, Gatti, Giacomina, Costa, Santini and Maffei https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Dattilo, Alessia
Ceccarini, Giovanni
Scabia, Gaia
Magno, Silvia
Quintino, Lara
Pelosini, Caterina
Salvetti, Guido
Cusano, Roberto
Massidda, Matteo
Montanelli, Lucia
Gilio, Donatella
Gatti, Gianluca
Giacomina, Alessandro
Costa, Mario
Santini, Ferruccio
Maffei, Margherita
Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease
title Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease
title_full Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease
title_fullStr Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease
title_full_unstemmed Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease
title_short Circulating Levels of MiRNAs From 320 Family in Subjects With Lipodystrophy: Disclosing Novel Signatures of the Disease
title_sort circulating levels of mirnas from 320 family in subjects with lipodystrophy: disclosing novel signatures of the disease
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207177/
https://www.ncbi.nlm.nih.gov/pubmed/35733784
http://dx.doi.org/10.3389/fendo.2022.866679
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