A pref-1-controlled non-inflammatory mechanism of insulin resistance
Summary: While insulin resistance (IR) is associated with inflammation in white adipose tissue, we report a non-inflammatory adipose mechanism of high fat-induced IR mediated by loss of Pref-1. Pref-1, released from adipose Pref-1+ cells with characteristics of M2 macrophages, endothelial cells or p...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223010003 |
| _version_ | 1797814337045266432 |
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| author | Yiheng Huang Donghong Cui Liujun Chen Haibin Tong Hong Wu Grace K. Muller Yadan Qi Shuxia Wang Jinjie Xu Xiang Gao Kathleen E. Fifield Lingyan Wang Zhengyuan Xia Jacqueline L. Vanderluit Suixin Liu Lin Leng Guang Sun John McGuire Lawrence H. Young Richard Bucala Dake Qi |
| author_facet | Yiheng Huang Donghong Cui Liujun Chen Haibin Tong Hong Wu Grace K. Muller Yadan Qi Shuxia Wang Jinjie Xu Xiang Gao Kathleen E. Fifield Lingyan Wang Zhengyuan Xia Jacqueline L. Vanderluit Suixin Liu Lin Leng Guang Sun John McGuire Lawrence H. Young Richard Bucala Dake Qi |
| author_sort | Yiheng Huang |
| collection | DOAJ |
| description | Summary: While insulin resistance (IR) is associated with inflammation in white adipose tissue, we report a non-inflammatory adipose mechanism of high fat-induced IR mediated by loss of Pref-1. Pref-1, released from adipose Pref-1+ cells with characteristics of M2 macrophages, endothelial cells or progenitors, inhibits MIF release from both Pref-1+ cells and adipocytes by binding with integrin β1 and inhibiting the mobilization of p115. High palmitic acid induces PAR2 expression in Pref-1+ cells, downregulating Pref-1 expression and release in an AMPK-dependent manner. The loss of Pref-1 increases adipose MIF secretion contributing to non-inflammatory IR in obesity. Treatment with Pref-1 blunts the increase in circulating plasma MIF levels and subsequent IR induced by a high palmitic acid diet. Thus, high levels of fatty acids suppress Pref-1 expression and secretion, through increased activation of PAR2, resulting in an increase in MIF secretion and a non-inflammatory adipose mechanism of IR. |
| first_indexed | 2024-03-13T08:06:11Z |
| format | Article |
| id | doaj.art-4fad11db6db3452e8ef0f35ff8313cab |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-13T08:06:11Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4fad11db6db3452e8ef0f35ff8313cab2023-06-01T04:36:48ZengElsevieriScience2589-00422023-06-01266106923A pref-1-controlled non-inflammatory mechanism of insulin resistanceYiheng Huang0Donghong Cui1Liujun Chen2Haibin Tong3Hong Wu4Grace K. Muller5Yadan Qi6Shuxia Wang7Jinjie Xu8Xiang Gao9Kathleen E. Fifield10Lingyan Wang11Zhengyuan Xia12Jacqueline L. Vanderluit13Suixin Liu14Lin Leng15Guang Sun16John McGuire17Lawrence H. Young18Richard Bucala19Dake Qi20College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaShanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaCollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaCollege of Life and Environment Sciences, Wenzhou University, Wenzhou, Zhejiang, ChinaInstitute of Cardiovascular Disease, Henan University of Chinese Medicine, Zhengzhou, Henan, ChinaDepartment of Cell and Molecular Physiology, Loyola University, Chicago, IL, USACollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Cardiology, The General Hospital of Chinese PLA, Beijing, ChinaBeijing Anding Hospital, Capital Medical University, Beijing, ChinaCollege of Life Sciences, Qingdao University, Qingdao, Shandong, ChinaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, CanadaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, CanadaGuangdong Medical University, Zhanjiang, ChinaDivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, CanadaDivision of Cardiac Rehabilitation, Department of Physical Medicine & Rehabilitation, Xiangya Hospital of Central South University, Changsha, Hunan, ChinaDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USADivision of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, CanadaDepartment of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON, CanadaDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USADepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USACollege of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Division of Biomedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL, Canada; Corresponding authorSummary: While insulin resistance (IR) is associated with inflammation in white adipose tissue, we report a non-inflammatory adipose mechanism of high fat-induced IR mediated by loss of Pref-1. Pref-1, released from adipose Pref-1+ cells with characteristics of M2 macrophages, endothelial cells or progenitors, inhibits MIF release from both Pref-1+ cells and adipocytes by binding with integrin β1 and inhibiting the mobilization of p115. High palmitic acid induces PAR2 expression in Pref-1+ cells, downregulating Pref-1 expression and release in an AMPK-dependent manner. The loss of Pref-1 increases adipose MIF secretion contributing to non-inflammatory IR in obesity. Treatment with Pref-1 blunts the increase in circulating plasma MIF levels and subsequent IR induced by a high palmitic acid diet. Thus, high levels of fatty acids suppress Pref-1 expression and secretion, through increased activation of PAR2, resulting in an increase in MIF secretion and a non-inflammatory adipose mechanism of IR.http://www.sciencedirect.com/science/article/pii/S2589004223010003Molecular biologyImmunologyCell biologyTranscriptomics |
| spellingShingle | Yiheng Huang Donghong Cui Liujun Chen Haibin Tong Hong Wu Grace K. Muller Yadan Qi Shuxia Wang Jinjie Xu Xiang Gao Kathleen E. Fifield Lingyan Wang Zhengyuan Xia Jacqueline L. Vanderluit Suixin Liu Lin Leng Guang Sun John McGuire Lawrence H. Young Richard Bucala Dake Qi A pref-1-controlled non-inflammatory mechanism of insulin resistance iScience Molecular biology Immunology Cell biology Transcriptomics |
| title | A pref-1-controlled non-inflammatory mechanism of insulin resistance |
| title_full | A pref-1-controlled non-inflammatory mechanism of insulin resistance |
| title_fullStr | A pref-1-controlled non-inflammatory mechanism of insulin resistance |
| title_full_unstemmed | A pref-1-controlled non-inflammatory mechanism of insulin resistance |
| title_short | A pref-1-controlled non-inflammatory mechanism of insulin resistance |
| title_sort | pref 1 controlled non inflammatory mechanism of insulin resistance |
| topic | Molecular biology Immunology Cell biology Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223010003 |
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