Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance
Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alter...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00696/full |
| _version_ | 1811216198394707968 |
|---|---|
| author | Youngjo Kim Princess Wendy Bayona Miri Kim Jiyeon Chang Sunmin Hong Yoona Park Andrea Budiman Yong-Jin Kim Chang Yong Choi Woo Seok Kim Jongsoon Lee Kae Won Cho |
| author_facet | Youngjo Kim Princess Wendy Bayona Miri Kim Jiyeon Chang Sunmin Hong Yoona Park Andrea Budiman Yong-Jin Kim Chang Yong Choi Woo Seok Kim Jongsoon Lee Kae Won Cho |
| author_sort | Youngjo Kim |
| collection | DOAJ |
| description | Obesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance. |
| first_indexed | 2024-04-12T06:35:18Z |
| format | Article |
| id | doaj.art-fd275467dad44ef3b372c4903b1251d1 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T06:35:18Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fd275467dad44ef3b372c4903b1251d12022-12-22T03:43:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00696329650Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin ResistanceYoungjo Kim0Princess Wendy Bayona1Miri Kim2Jiyeon Chang3Sunmin Hong4Yoona Park5Andrea Budiman6Yong-Jin Kim7Chang Yong Choi8Woo Seok Kim9Jongsoon Lee10Kae Won Cho11Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaDepartment of Surgery, Soonchunhyang University Hospital, Seoul, South KoreaDepartment of Plastic and Reconstructive Surgery, Soonchunhyang University Hospital, Gumi, South KoreaDepartment of Surgery, Soonchunhyang University Gumi Hospital, Gumi, South KoreaThe Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, MA, United StatesSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheon-an, South KoreaObesity-induced chronic low-grade inflammation, in particular in adipose tissue, contributes to the development of insulin resistance and type 2 diabetes. However, the mechanism by which obesity induces adipose tissue inflammation has not been completely elucidated. Recent studies suggest that alteration of the nuclear lamina is associated with age-associated chronic inflammation in humans and fly. These findings led us to investigate whether the nuclear lamina regulates obesity-mediated chronic inflammation. In this study, we show that lamin A/C mediates inflammation in macrophages. The gene and protein expression levels of lamin A/C are significantly increased in epididymal adipose tissues from obese rodent models and omental fat from obese human subjects compared to their lean controls. Flow cytometry and gene expression analyses reveal that the protein and gene expression levels of lamin A/C are increased in adipose tissue macrophages (ATMs) by obesity. We further show that ectopic overexpression of lamin A/C in macrophages spontaneously activates NF-κB, and increases the gene expression levels of proinflammatory genes, such as Il6, Tnf, Ccl2, and Nos2. Conversely, deletion of lamin A/C in macrophages reduces LPS-induced expression of these proinflammatory genes. Importantly, we find that myeloid cell-specific lamin A/C deficiency ameliorates obesity-induced insulin resistance and adipose tissue inflammation. Thus, our data suggest that lamin A/C mediates the activation of ATM inflammation by regulating NF-κB, thereby contributing to the development of obesity-induced insulin resistance.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00696/fulllamin A/Cobesityinflammationinsulin resistancemacrophagesadipose tissue |
| spellingShingle | Youngjo Kim Princess Wendy Bayona Miri Kim Jiyeon Chang Sunmin Hong Yoona Park Andrea Budiman Yong-Jin Kim Chang Yong Choi Woo Seok Kim Jongsoon Lee Kae Won Cho Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance Frontiers in Immunology lamin A/C obesity inflammation insulin resistance macrophages adipose tissue |
| title | Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance |
| title_full | Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance |
| title_fullStr | Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance |
| title_full_unstemmed | Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance |
| title_short | Macrophage Lamin A/C Regulates Inflammation and the Development of Obesity-Induced Insulin Resistance |
| title_sort | macrophage lamin a c regulates inflammation and the development of obesity induced insulin resistance |
| topic | lamin A/C obesity inflammation insulin resistance macrophages adipose tissue |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00696/full |
| work_keys_str_mv | AT youngjokim macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT princesswendybayona macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT mirikim macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT jiyeonchang macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT sunminhong macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT yoonapark macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT andreabudiman macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT yongjinkim macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT changyongchoi macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT wooseokkim macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT jongsoonlee macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance AT kaewoncho macrophagelaminacregulatesinflammationandthedevelopmentofobesityinducedinsulinresistance |