The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.

The prevalence of non-alcoholic fatty-liver disease (NAFLD) is increasing globally. NAFLD is a spectrum of related liver diseases that progressive from simple steatosis to serious complications like cirrhosis. The major pathophysiological driving of NAFLD includes elevated hepatic adiposity, increas...

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Autores principales:	Tatiana Ntube Salley, Manish Mishra, Shuchita Tiwari, Ashok Jadhav, Joseph Fomusi Ndisang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c166a91c05ff447c8376536f3176defd
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spelling	oai:doaj.org-article:c166a91c05ff447c8376536f3176defd2021-11-18T08:46:10ZThe heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.1932-620310.1371/journal.pone.0079270https://doaj.org/article/c166a91c05ff447c8376536f3176defd2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24260182/?tool=EBIhttps://doaj.org/toc/1932-6203The prevalence of non-alcoholic fatty-liver disease (NAFLD) is increasing globally. NAFLD is a spectrum of related liver diseases that progressive from simple steatosis to serious complications like cirrhosis. The major pathophysiological driving of NAFLD includes elevated hepatic adiposity, increased hepatic triglycerides/cholesterol, excessive hepatic inflammation, and hepatocyte ballooning injury is a common histo-pathological denominator. Although heme-oxygenase (HO) is cytoprotective, its effects on hepatocyte ballooning injury have not been reported. We investigated the effects of upregulating HO with hemin or inhibiting it with stannous-mesoporphyrin (SnMP) on hepatocyte ballooning injury, hepatic adiposity and inflammation in Zucker-diabetic-fatty rats (ZDFs), an obese type-2-diabetic model. Hemin administration to ZDFs abated hepatic/plasma triglycerides and cholesterol, and suppressed several pro-inflammatory cytokines and chemokines including, TNF-α, IL-6, IL-1β, macrophage-inflammatory-protein-1α (MIP-1α) and macrophage-chemoattractant-protein-1 (MCP-1), with corresponding reduction of the pro-inflammatory M1-phenotype marker, ED1 and hepatic macrophage infiltration. Correspondingly, hemin concomitantly potentiated the protein expression of several markers of the anti-inflammatory macrophage-M2-phenotype including ED2, IL-10 and CD-206, alongside components of the HO-system including HO-1, HO-activity and cGMP, whereas the HO-inhibitor, SnMP abolished the effects. Furthermore, hemin attenuated liver histo-pathological lesions like hepatocyte ballooning injury and fibrosis, and reduced extracellular-matrix/profibrotic proteins implicated in liver injury such as osteopontin, TGF-β1, fibronectin and collagen-IV. We conclude that hemin restore hepatic morphology by abating hepatic adiposity, suppressing macrophage infiltration, inflammation and fibrosis. The selective enhancement of anti-inflammatory macrophage-M2-phenotype with parallel reduction of pro-inflammatory macrophage-M1-phenotype and related chemokines/cytokines like TNF-α, IL-6, IL-1β, MIP-1α and MCP-1 are among the multifaceted mechanisms by which hemin restore hepatic morphology.Tatiana Ntube SalleyManish MishraShuchita TiwariAshok JadhavJoseph Fomusi NdisangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e79270 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tatiana Ntube Salley Manish Mishra Shuchita Tiwari Ashok Jadhav Joseph Fomusi Ndisang The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
description	The prevalence of non-alcoholic fatty-liver disease (NAFLD) is increasing globally. NAFLD is a spectrum of related liver diseases that progressive from simple steatosis to serious complications like cirrhosis. The major pathophysiological driving of NAFLD includes elevated hepatic adiposity, increased hepatic triglycerides/cholesterol, excessive hepatic inflammation, and hepatocyte ballooning injury is a common histo-pathological denominator. Although heme-oxygenase (HO) is cytoprotective, its effects on hepatocyte ballooning injury have not been reported. We investigated the effects of upregulating HO with hemin or inhibiting it with stannous-mesoporphyrin (SnMP) on hepatocyte ballooning injury, hepatic adiposity and inflammation in Zucker-diabetic-fatty rats (ZDFs), an obese type-2-diabetic model. Hemin administration to ZDFs abated hepatic/plasma triglycerides and cholesterol, and suppressed several pro-inflammatory cytokines and chemokines including, TNF-α, IL-6, IL-1β, macrophage-inflammatory-protein-1α (MIP-1α) and macrophage-chemoattractant-protein-1 (MCP-1), with corresponding reduction of the pro-inflammatory M1-phenotype marker, ED1 and hepatic macrophage infiltration. Correspondingly, hemin concomitantly potentiated the protein expression of several markers of the anti-inflammatory macrophage-M2-phenotype including ED2, IL-10 and CD-206, alongside components of the HO-system including HO-1, HO-activity and cGMP, whereas the HO-inhibitor, SnMP abolished the effects. Furthermore, hemin attenuated liver histo-pathological lesions like hepatocyte ballooning injury and fibrosis, and reduced extracellular-matrix/profibrotic proteins implicated in liver injury such as osteopontin, TGF-β1, fibronectin and collagen-IV. We conclude that hemin restore hepatic morphology by abating hepatic adiposity, suppressing macrophage infiltration, inflammation and fibrosis. The selective enhancement of anti-inflammatory macrophage-M2-phenotype with parallel reduction of pro-inflammatory macrophage-M1-phenotype and related chemokines/cytokines like TNF-α, IL-6, IL-1β, MIP-1α and MCP-1 are among the multifaceted mechanisms by which hemin restore hepatic morphology.
format	article
author	Tatiana Ntube Salley Manish Mishra Shuchita Tiwari Ashok Jadhav Joseph Fomusi Ndisang
author_facet	Tatiana Ntube Salley Manish Mishra Shuchita Tiwari Ashok Jadhav Joseph Fomusi Ndisang
author_sort	Tatiana Ntube Salley
title	The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
title_short	The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
title_full	The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
title_fullStr	The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
title_full_unstemmed	The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
title_sort	heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c166a91c05ff447c8376536f3176defd
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The heme oxygenase system rescues hepatic deterioration in the condition of obesity co-morbid with type-2 diabetes.

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