Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD

The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Anna-Sophia Leven, Robert K. Gieseler, Martin Schlattjan, Thomas Schreiter, Marco Niedergethmann, Theodor Baars, Hideo A. Baba, Mustafa K. Özçürümez, Jan-Peter Sowa, Ali Canbay
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	adipocyte size apoptosis autophagy collagen necroptosis necrosis pyroptosis Diseases of the endocrine glands. Clinical endocrinology RC648-665 Cytology QH573-671 Physiology QP1-981
Acceso en línea:	https://doaj.org/article/845cd90359424267aa600f842a6842c3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:845cd90359424267aa600f842a6842c3
record_format	dspace
spelling	oai:doaj.org-article:845cd90359424267aa600f842a6842c32021-11-26T11:19:49ZAssociation of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD2162-39452162-397X10.1080/21623945.2021.1982164https://doaj.org/article/845cd90359424267aa600f842a6842c32021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/21623945.2021.1982164https://doaj.org/toc/2162-3945https://doaj.org/toc/2162-397XThe role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression. Abbreviations: ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson’s correlation coefficient (r); rs: Spearman’s rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissueAnna-Sophia LevenRobert K. GieselerMartin SchlattjanThomas SchreiterMarco NiedergethmannTheodor BaarsHideo A. BabaMustafa K. ÖzçürümezJan-Peter SowaAli CanbayTaylor & Francis Grouparticleadipocyte sizeapoptosisautophagycollagennecroptosisnecrosispyroptosisDiseases of the endocrine glands. Clinical endocrinologyRC648-665CytologyQH573-671PhysiologyQP1-981ENAdipocyte, Vol 10, Iss 1, Pp 558-573 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	adipocyte size apoptosis autophagy collagen necroptosis necrosis pyroptosis Diseases of the endocrine glands. Clinical endocrinology RC648-665 Cytology QH573-671 Physiology QP1-981
spellingShingle	adipocyte size apoptosis autophagy collagen necroptosis necrosis pyroptosis Diseases of the endocrine glands. Clinical endocrinology RC648-665 Cytology QH573-671 Physiology QP1-981 Anna-Sophia Leven Robert K. Gieseler Martin Schlattjan Thomas Schreiter Marco Niedergethmann Theodor Baars Hideo A. Baba Mustafa K. Özçürümez Jan-Peter Sowa Ali Canbay Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD
description	The role of visceral white adipose tissue (vWAT) in the progression of non-alcoholic liver disease (NAFLD) with its sub entities non-alcoholic fatty liver and steatohepatitis (NAFL; NASH) is underinvestigated. We thus explored mechanisms of fibrosis and regulated cell death in vWAT and liver tissue. In NAFLD, women displayed significantly more fibrosis in vWAT than men, and collagen 1α mRNA expression was significantly upregulated. The degrees of fibrosis in vWAT and liver tissue correlated significantly. The size of vWAT-resident adipocytes in NAFLD correlated negatively with the local degree of fibrosis. The extent of apoptosis, as measured by circulating M30, positively correlated with the degree of fibrosis in vWAT; necrosis-associated HMGB1 mRNA expression was significantly downregulated in vWAT and liver tissue; (iii) necroptosis-related RIPK-3 mRNA expression was significantly upregulated in vWAT; and autophagy-related LC3 mRNA expression was significantly downregulated in vWAT, while upregulated in the liver. Thus, the different cell death mechanisms in the vWAT in NAFLD are regulated independently while not ruling out their interaction. Fibrosis in vWAT may be associated with reduced adipocyte size and thus partially protective against NAFLD progression. Abbreviations: ATG5: autophagy related 5; BAS: bariatric surgery; BMI: body mass index; ELISA: enzyme-linked immunosorbent assay; EtOH: ethanol; FFAs: free fatty acids; HCC: hepatocellular carcinoma; HMGB1: high-mobility group box 1 protein; IHC: immunohistochemistry; IL: interleukin; LC3: microtubule-associated proteins 1A/1B light chain 3B; M30: neoepitope K18Asp396-NE displayed on the caspase-cleaved keratin 18 fragment; M65: epitope present on both caspase-cleaved and intact keratin 18; NAFL: non-alcoholic fatty liver; NAFLD: non-alcoholic fatty liver disease; NAS: NAFLD activity score; NASH: non-alcoholic steatohepatitis; NLRP3: nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3; qRT-PCR: quantitative real-time polymerase-chain reaction; r: Pearson’s correlation coefficient (r); rs: Spearman’s rank correlation coefficient; RIPK3: receptor-interacting serine/threonine-protein kinase 3; T2DM: type 2 diabetes mellitus (T2DM); TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling; vWAT: visceral WAT; WAT: white adipose tissue
format	article
author	Anna-Sophia Leven Robert K. Gieseler Martin Schlattjan Thomas Schreiter Marco Niedergethmann Theodor Baars Hideo A. Baba Mustafa K. Özçürümez Jan-Peter Sowa Ali Canbay
author_facet	Anna-Sophia Leven Robert K. Gieseler Martin Schlattjan Thomas Schreiter Marco Niedergethmann Theodor Baars Hideo A. Baba Mustafa K. Özçürümez Jan-Peter Sowa Ali Canbay
author_sort	Anna-Sophia Leven
title	Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD
title_short	Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD
title_full	Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD
title_fullStr	Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD
title_full_unstemmed	Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD
title_sort	association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with nafld
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/845cd90359424267aa600f842a6842c3
work_keys_str_mv	AT annasophialeven associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT robertkgieseler associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT martinschlattjan associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT thomasschreiter associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT marconiedergethmann associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT theodorbaars associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT hideoababa associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT mustafakozcurumez associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT janpetersowa associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld AT alicanbay associationofcelldeathmechanismsandfibrosisinvisceralwhiteadiposetissuewithpathologicalalterationsintheliverofmorbidlyobesepatientswithnafld
_version_	1718409482734665728

Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alterations in the liver of morbidly obese patients with NAFLD

Ejemplares similares