Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

XianFeng Wang, Nancy L Buechler, Barbara K Yoza, Charles E McCall, Vidula Vachharajani Department of Anesthesiology, Medicine and Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Morbid obesity increases the cost of care in critically ill patient...

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Autores principales:	Wang X, Buechler NL, Yoza BK, McCall CE, Vachharajani V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	1) Obesity 2) Sepsis 3) Leukocyte adhesion 4) Sirtuin-1 5) Adiponectin Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d7f1d9b4660c4c03b044a5c61a38f960
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spelling	oai:doaj.org-article:d7f1d9b4660c4c03b044a5c61a38f9602021-12-02T02:50:16ZAdiponectin treatment attenuates inflammatory response during early sepsis in obese mice1178-7031https://doaj.org/article/d7f1d9b4660c4c03b044a5c61a38f9602016-10-01T00:00:00Zhttps://www.dovepress.com/adiponectin-treatment-attenuates-inflammatory-response-during-early-se-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031XianFeng Wang, Nancy L Buechler, Barbara K Yoza, Charles E McCall, Vidula Vachharajani Department of Anesthesiology, Medicine and Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell–endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis. In the present study, we investigated the effect of adiponectin replacement on nutritionally obese mice with early sepsis. Methods: We used cecal ligation and puncture model of sepsis in mice with diet-induced obesity (DIO) vs control diet (CTRL), with or without adiponectin treatment. We studied leukocyte/platelet adhesion in the cerebral microcirculation in early sepsis. We also studied the effect of adiponectin on free fatty acid (FFA)-fed and lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDM) for mechanistic studies. Results: Leukocyte and platelet adhesion increased in the cerebral microcirculation of DIO and CTRL mice with early sepsis vs. sham; moreover cell adhesion in DIO-sepsis group was significantly higher than in the CTRL-sepsis group. Adiponectin replacement decreased leukocyte/platelet adhesion in CTRL and DIO mice. In FFA-fed BMDM, adiponectin treatment decreased tumor necrosis factor-alpha mRNA expression and increased sirtuin-1 (SIRT1) mRNA expression. Furthermore, using BMDM from SIRT1 knockout mice, we showed that the adiponectin treatment decreased inflammatory response in FFA-fed BMDM via SIRT1-dependent and -independent pathways. Conclusion: Adiponectin replacement attenuates microvascular inflammation in DIO-sepsis mice. Mechanistically, adiponectin treatment in FFA-fed mouse macrophages attenuates inflammatory response via SIRT1-dependent and -independent pathways. Keywords: sepsis, obesity, adiponectin, leukocyte adhesion, inflammation, sirtuin-1Wang XBuechler NLYoza BKMcCall CEVachharajani VDove Medical Pressarticle1) Obesity2) Sepsis3) Leukocyte adhesion4) Sirtuin-15) AdiponectinPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 9, Pp 167-174 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	1) Obesity 2) Sepsis 3) Leukocyte adhesion 4) Sirtuin-1 5) Adiponectin Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	1) Obesity 2) Sepsis 3) Leukocyte adhesion 4) Sirtuin-1 5) Adiponectin Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Wang X Buechler NL Yoza BK McCall CE Vachharajani V Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
description	XianFeng Wang, Nancy L Buechler, Barbara K Yoza, Charles E McCall, Vidula Vachharajani Department of Anesthesiology, Medicine and Surgery, Wake Forest School of Medicine, Winston-Salem, NC, USA Background: Morbid obesity increases the cost of care in critically ill patients. Sepsis is the leading cause of death in noncoronary intensive care units. Circulating cell–endothelial cell interactions in microcirculation are the rate-determining factors in any inflammation; obesity increases these interactions further. Adiponectin deficiency is implicated in increased cardiovascular risk in obese patients. We have shown that adiponectin deficiency increases microvascular dysfunction in early sepsis. In the present study, we investigated the effect of adiponectin replacement on nutritionally obese mice with early sepsis. Methods: We used cecal ligation and puncture model of sepsis in mice with diet-induced obesity (DIO) vs control diet (CTRL), with or without adiponectin treatment. We studied leukocyte/platelet adhesion in the cerebral microcirculation in early sepsis. We also studied the effect of adiponectin on free fatty acid (FFA)-fed and lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDM) for mechanistic studies. Results: Leukocyte and platelet adhesion increased in the cerebral microcirculation of DIO and CTRL mice with early sepsis vs. sham; moreover cell adhesion in DIO-sepsis group was significantly higher than in the CTRL-sepsis group. Adiponectin replacement decreased leukocyte/platelet adhesion in CTRL and DIO mice. In FFA-fed BMDM, adiponectin treatment decreased tumor necrosis factor-alpha mRNA expression and increased sirtuin-1 (SIRT1) mRNA expression. Furthermore, using BMDM from SIRT1 knockout mice, we showed that the adiponectin treatment decreased inflammatory response in FFA-fed BMDM via SIRT1-dependent and -independent pathways. Conclusion: Adiponectin replacement attenuates microvascular inflammation in DIO-sepsis mice. Mechanistically, adiponectin treatment in FFA-fed mouse macrophages attenuates inflammatory response via SIRT1-dependent and -independent pathways. Keywords: sepsis, obesity, adiponectin, leukocyte adhesion, inflammation, sirtuin-1
format	article
author	Wang X Buechler NL Yoza BK McCall CE Vachharajani V
author_facet	Wang X Buechler NL Yoza BK McCall CE Vachharajani V
author_sort	Wang X
title	Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
title_short	Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
title_full	Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
title_fullStr	Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
title_full_unstemmed	Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
title_sort	adiponectin treatment attenuates inflammatory response during early sepsis in obese mice
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/d7f1d9b4660c4c03b044a5c61a38f960
work_keys_str_mv	AT wangx adiponectintreatmentattenuatesinflammatoryresponseduringearlysepsisinobesemice AT buechlernl adiponectintreatmentattenuatesinflammatoryresponseduringearlysepsisinobesemice AT yozabk adiponectintreatmentattenuatesinflammatoryresponseduringearlysepsisinobesemice AT mccallce adiponectintreatmentattenuatesinflammatoryresponseduringearlysepsisinobesemice AT vachharajaniv adiponectintreatmentattenuatesinflammatoryresponseduringearlysepsisinobesemice
_version_	1718402130489901056

Adiponectin treatment attenuates inflammatory response during early sepsis in obese mice

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