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High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation

OBJECTIVE: Previous studies have demonstrated that mice fed a high-fat diet (HFD) develop insulin resistance with proinflammatory macrophage infiltration into white adipose tissue. Concomitantly, adipocytes undergo programmed cell death with the loss of the adipocyte-specific lipid droplet protein p...

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Autores principales: Feng, Daorong, Tang, Yan, Kwon, Hyokjoon, Zong, Haihong, Hawkins, Meredith, Kitsis, Richard N., Pessin, Jeffrey E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142076/
https://www.ncbi.nlm.nih.gov/pubmed/21734017
http://dx.doi.org/10.2337/db10-1411
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author Feng, Daorong
Tang, Yan
Kwon, Hyokjoon
Zong, Haihong
Hawkins, Meredith
Kitsis, Richard N.
Pessin, Jeffrey E.
author_facet Feng, Daorong
Tang, Yan
Kwon, Hyokjoon
Zong, Haihong
Hawkins, Meredith
Kitsis, Richard N.
Pessin, Jeffrey E.
author_sort Feng, Daorong
collection PubMed
description OBJECTIVE: Previous studies have demonstrated that mice fed a high-fat diet (HFD) develop insulin resistance with proinflammatory macrophage infiltration into white adipose tissue. Concomitantly, adipocytes undergo programmed cell death with the loss of the adipocyte-specific lipid droplet protein perilipin, and the dead/dying adipocytes are surrounded by macrophages that are organized into crown-like structures. This study investigated whether adipocyte cell death provides the driving signal for macrophage inflammation or if inflammation induces adipocyte cell death. RESEARCH DESIGN AND METHODS: Two knockout mouse models were used: granulocyte/monocyte-colony stimulating factor (GM-CSF)–null mice that are protected against HFD-induced adipose tissue inflammation and cyclophilin D (CyP-D)–null mice that are protected against adipocyte cell death. Mice were fed for 4–14 weeks with a 60% HFD, and different markers of cell death and inflammation were analyzed. RESULTS: HFD induced a normal extent of adipocyte cell death in GM-CSF–null mice, despite a marked reduction in adipose tissue inflammation. Similarly, depletion of macrophages by clodronate treatment prevented HFD-induced adipose tissue inflammation without any affect on adipocyte cell death. However, CyP-D deficiency strongly protected adipocytes from HFD-induced cell death, without affecting adipose tissue inflammation. CONCLUSIONS: These data demonstrate that HFD-induced adipocyte cell death is an intrinsic cellular response that is CyP-D dependent but is independent of macrophage infiltration/activation.
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spelling pubmed-31420762012-08-01 High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation Feng, Daorong Tang, Yan Kwon, Hyokjoon Zong, Haihong Hawkins, Meredith Kitsis, Richard N. Pessin, Jeffrey E. Diabetes Immunology and Transplantation OBJECTIVE: Previous studies have demonstrated that mice fed a high-fat diet (HFD) develop insulin resistance with proinflammatory macrophage infiltration into white adipose tissue. Concomitantly, adipocytes undergo programmed cell death with the loss of the adipocyte-specific lipid droplet protein perilipin, and the dead/dying adipocytes are surrounded by macrophages that are organized into crown-like structures. This study investigated whether adipocyte cell death provides the driving signal for macrophage inflammation or if inflammation induces adipocyte cell death. RESEARCH DESIGN AND METHODS: Two knockout mouse models were used: granulocyte/monocyte-colony stimulating factor (GM-CSF)–null mice that are protected against HFD-induced adipose tissue inflammation and cyclophilin D (CyP-D)–null mice that are protected against adipocyte cell death. Mice were fed for 4–14 weeks with a 60% HFD, and different markers of cell death and inflammation were analyzed. RESULTS: HFD induced a normal extent of adipocyte cell death in GM-CSF–null mice, despite a marked reduction in adipose tissue inflammation. Similarly, depletion of macrophages by clodronate treatment prevented HFD-induced adipose tissue inflammation without any affect on adipocyte cell death. However, CyP-D deficiency strongly protected adipocytes from HFD-induced cell death, without affecting adipose tissue inflammation. CONCLUSIONS: These data demonstrate that HFD-induced adipocyte cell death is an intrinsic cellular response that is CyP-D dependent but is independent of macrophage infiltration/activation. American Diabetes Association 2011-08 2011-07-18 /pmc/articles/PMC3142076/ /pubmed/21734017 http://dx.doi.org/10.2337/db10-1411 Text en © 2011 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Immunology and Transplantation
Feng, Daorong
Tang, Yan
Kwon, Hyokjoon
Zong, Haihong
Hawkins, Meredith
Kitsis, Richard N.
Pessin, Jeffrey E.
High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation
title High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation
title_full High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation
title_fullStr High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation
title_full_unstemmed High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation
title_short High-Fat Diet–Induced Adipocyte Cell Death Occurs Through a Cyclophilin D Intrinsic Signaling Pathway Independent of Adipose Tissue Inflammation
title_sort high-fat diet–induced adipocyte cell death occurs through a cyclophilin d intrinsic signaling pathway independent of adipose tissue inflammation
topic Immunology and Transplantation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142076/
https://www.ncbi.nlm.nih.gov/pubmed/21734017
http://dx.doi.org/10.2337/db10-1411
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