Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S]
Mechanistic target of rapamycin complex (mTORC)1 activity is increased in adipose tissue of obese insulin-resistant mice, but its role in the regulation of tissue inflammation is unknown. Herein, we investigated the effects of adipocyte mTORC1 deficiency on adipose tissue inflammation and glucose ho...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-09-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520339511 |
| _version_ | 1818690630801424384 |
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| author | Patricia Chimin Maynara L. Andrade Thiago Belchior Vivian A. Paschoal Juliana Magdalon Alex S. Yamashita Érique Castro Angela Castoldi Adriano B. Chaves-Filho Marcos Y. Yoshinaga Sayuri Miyamoto Niels O. Câmara William T. Festuccia |
| author_facet | Patricia Chimin Maynara L. Andrade Thiago Belchior Vivian A. Paschoal Juliana Magdalon Alex S. Yamashita Érique Castro Angela Castoldi Adriano B. Chaves-Filho Marcos Y. Yoshinaga Sayuri Miyamoto Niels O. Câmara William T. Festuccia |
| author_sort | Patricia Chimin |
| collection | DOAJ |
| description | Mechanistic target of rapamycin complex (mTORC)1 activity is increased in adipose tissue of obese insulin-resistant mice, but its role in the regulation of tissue inflammation is unknown. Herein, we investigated the effects of adipocyte mTORC1 deficiency on adipose tissue inflammation and glucose homeostasis. For this, mice with adipocyte raptor deletion and controls fed a chow or a high-fat diet were evaluated for body mass, adiposity, glucose homeostasis, and adipose tissue inflammation. Despite reducing adiposity, adipocyte mTORC1 deficiency promoted hepatic steatosis, insulin resistance, and adipose tissue inflammation (increased infiltration of macrophages, neutrophils, and B lymphocytes; crown-like structure density; TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 expression; IL-1β protein content; lipid peroxidation; and de novo ceramide synthesis). The anti-oxidant, N-acetylcysteine, partially attenuated, whereas treatment with de novo ceramide synthesis inhibitor, myriocin, completely blocked adipose tissue inflammation and nucleotide oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3)-inflammasome activation, but not hepatic steatosis and insulin resistance induced by adipocyte raptor deletion. Rosiglitazone treatment, however, completely abrogated insulin resistance induced by adipocyte raptor deletion. In conclusion, adipocyte mTORC1 deficiency induces adipose tissue inflammation and NLRP3-inflammasome activation by promoting oxidative stress and de novo ceramide synthesis. Such adipose tissue inflammation, however, is not an underlying cause of the insulin resistance displayed by these mice. |
| first_indexed | 2024-12-17T12:29:04Z |
| format | Article |
| id | doaj.art-52615403df4840119ad4c2c43856f4a0 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T12:29:04Z |
| publishDate | 2017-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-52615403df4840119ad4c2c43856f4a02022-12-21T21:48:41ZengElsevierJournal of Lipid Research0022-22752017-09-0158917971807Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S]Patricia Chimin0Maynara L. Andrade1Thiago Belchior2Vivian A. Paschoal3Juliana Magdalon4Alex S. Yamashita5Érique Castro6Angela Castoldi7Adriano B. Chaves-Filho8Marcos Y. Yoshinaga9Sayuri Miyamoto10Niels O. Câmara11William T. Festuccia12Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000; Department of Physical Education, Physical Education and Sports Center, Londrina State University, Parana, Brazil 86051-990Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil 05508000Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil 05508000Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil 05508000Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, Brazil 05508000Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil 05508000To whom correspondence should be addressed.; Departments of Physiology and Biophysics University of Sao Paulo, Sao Paulo, Brazil 05508000; To whom correspondence should be addressed.Mechanistic target of rapamycin complex (mTORC)1 activity is increased in adipose tissue of obese insulin-resistant mice, but its role in the regulation of tissue inflammation is unknown. Herein, we investigated the effects of adipocyte mTORC1 deficiency on adipose tissue inflammation and glucose homeostasis. For this, mice with adipocyte raptor deletion and controls fed a chow or a high-fat diet were evaluated for body mass, adiposity, glucose homeostasis, and adipose tissue inflammation. Despite reducing adiposity, adipocyte mTORC1 deficiency promoted hepatic steatosis, insulin resistance, and adipose tissue inflammation (increased infiltration of macrophages, neutrophils, and B lymphocytes; crown-like structure density; TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 expression; IL-1β protein content; lipid peroxidation; and de novo ceramide synthesis). The anti-oxidant, N-acetylcysteine, partially attenuated, whereas treatment with de novo ceramide synthesis inhibitor, myriocin, completely blocked adipose tissue inflammation and nucleotide oligomerization domain-like receptor pyrin domain-containing 3 (NLRP3)-inflammasome activation, but not hepatic steatosis and insulin resistance induced by adipocyte raptor deletion. Rosiglitazone treatment, however, completely abrogated insulin resistance induced by adipocyte raptor deletion. In conclusion, adipocyte mTORC1 deficiency induces adipose tissue inflammation and NLRP3-inflammasome activation by promoting oxidative stress and de novo ceramide synthesis. Such adipose tissue inflammation, however, is not an underlying cause of the insulin resistance displayed by these mice.http://www.sciencedirect.com/science/article/pii/S0022227520339511mechanistic target of rapamycin complex 1nucleotide oligomerization domain-like receptor pyrin domain-containing 3insulin resistance |
| spellingShingle | Patricia Chimin Maynara L. Andrade Thiago Belchior Vivian A. Paschoal Juliana Magdalon Alex S. Yamashita Érique Castro Angela Castoldi Adriano B. Chaves-Filho Marcos Y. Yoshinaga Sayuri Miyamoto Niels O. Câmara William T. Festuccia Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S] Journal of Lipid Research mechanistic target of rapamycin complex 1 nucleotide oligomerization domain-like receptor pyrin domain-containing 3 insulin resistance |
| title | Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S] |
| title_full | Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S] |
| title_fullStr | Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S] |
| title_full_unstemmed | Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S] |
| title_short | Adipocyte mTORC1 deficiency promotes adipose tissue inflammation and NLRP3 inflammasome activation via oxidative stress and de novo ceramide synthesis[S] |
| title_sort | adipocyte mtorc1 deficiency promotes adipose tissue inflammation and nlrp3 inflammasome activation via oxidative stress and de novo ceramide synthesis s |
| topic | mechanistic target of rapamycin complex 1 nucleotide oligomerization domain-like receptor pyrin domain-containing 3 insulin resistance |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520339511 |
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