Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity
Abstract Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-03-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-84828-z |
| _version_ | 1819202213626511360 |
|---|---|
| author | Maria A. Gonzalez Porras Katerina Stojkova Marcella K. Vaicik Amanda Pelowe Anna Goddi Alanis Carmona Byron Long Amina A. Qutub Anjelica Gonzalez Ronald N. Cohen Eric M. Brey |
| author_facet | Maria A. Gonzalez Porras Katerina Stojkova Marcella K. Vaicik Amanda Pelowe Anna Goddi Alanis Carmona Byron Long Amina A. Qutub Anjelica Gonzalez Ronald N. Cohen Eric M. Brey |
| author_sort | Maria A. Gonzalez Porras |
| collection | DOAJ |
| description | Abstract Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited. Mice with a null mutation in the laminin α4 (LAMA4) gene (KO) exhibit resistance to obesity and enhanced expression of thermogenic fat markers in white adipose tissue (WAT). In this study, changes in WAT extracellular matrix composition in the absence of LAMA4 were evaluated using liquid chromatography/tandem mass spectrometry. KO-mice showed lower levels of collagen 1A1 and 3A1, and integrins α7 (ITA7) and β1 (ITB1). ITA7-ITB1 and collagen 1A1-3A1 protein levels were lower in brown adipose tissue compared to WAT in wild-type mice. Immunohistochemical staining confirmed lower levels and different spatial distribution of ITA7 in KO-WAT. In culture studies, ITA7 and LAMA4 levels decreased following a 12-day differentiation of adipose-derived stem cells into beige fat, and knock-down of ITA7 during differentiation increased beiging. These results demonstrate that extracellular matrix interactions regulate adipocyte thermogenic capacity and that ITA7 plays a role in beige adipose formation. A better understanding of the mechanisms underlying these interactions can be used to improve systemic energy metabolism and glucose homeostasis. |
| first_indexed | 2024-12-23T04:00:27Z |
| format | Article |
| id | doaj.art-3451950b09ec48718aecf16f21d6e0f5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-23T04:00:27Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3451950b09ec48718aecf16f21d6e0f52022-12-21T18:00:44ZengNature PortfolioScientific Reports2045-23222021-03-0111111410.1038/s41598-021-84828-zIntegrins and extracellular matrix proteins modulate adipocyte thermogenic capacityMaria A. Gonzalez Porras0Katerina Stojkova1Marcella K. Vaicik2Amanda Pelowe3Anna Goddi4Alanis Carmona5Byron Long6Amina A. Qutub7Anjelica Gonzalez8Ronald N. Cohen9Eric M. Brey10Department of Biomedical Engineering and Chemical Engineering, AET 1.102, The University of Texas at San AntonioDepartment of Biomedical Engineering and Chemical Engineering, AET 1.102, The University of Texas at San AntonioDepartment of Biomedical Engineering, Illinois Institute of TechnologyDepartment of Biomedical Engineering, Yale UniversitySection of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of ChicagoSection of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of ChicagoDepartment of Biomedical Engineering and Chemical Engineering, AET 1.102, The University of Texas at San AntonioDepartment of Biomedical Engineering and Chemical Engineering, AET 1.102, The University of Texas at San AntonioDepartment of Biomedical Engineering, Yale UniversitySection of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of ChicagoDepartment of Biomedical Engineering and Chemical Engineering, AET 1.102, The University of Texas at San AntonioAbstract Obesity and the metabolic disease epidemic has led to an increase in morbidity and mortality. A rise in adipose thermogenic capacity via activation of brown or beige fat is a potential treatment for metabolic diseases. However, an understanding of how local factors control adipocyte fate is limited. Mice with a null mutation in the laminin α4 (LAMA4) gene (KO) exhibit resistance to obesity and enhanced expression of thermogenic fat markers in white adipose tissue (WAT). In this study, changes in WAT extracellular matrix composition in the absence of LAMA4 were evaluated using liquid chromatography/tandem mass spectrometry. KO-mice showed lower levels of collagen 1A1 and 3A1, and integrins α7 (ITA7) and β1 (ITB1). ITA7-ITB1 and collagen 1A1-3A1 protein levels were lower in brown adipose tissue compared to WAT in wild-type mice. Immunohistochemical staining confirmed lower levels and different spatial distribution of ITA7 in KO-WAT. In culture studies, ITA7 and LAMA4 levels decreased following a 12-day differentiation of adipose-derived stem cells into beige fat, and knock-down of ITA7 during differentiation increased beiging. These results demonstrate that extracellular matrix interactions regulate adipocyte thermogenic capacity and that ITA7 plays a role in beige adipose formation. A better understanding of the mechanisms underlying these interactions can be used to improve systemic energy metabolism and glucose homeostasis.https://doi.org/10.1038/s41598-021-84828-z |
| spellingShingle | Maria A. Gonzalez Porras Katerina Stojkova Marcella K. Vaicik Amanda Pelowe Anna Goddi Alanis Carmona Byron Long Amina A. Qutub Anjelica Gonzalez Ronald N. Cohen Eric M. Brey Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity Scientific Reports |
| title | Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity |
| title_full | Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity |
| title_fullStr | Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity |
| title_full_unstemmed | Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity |
| title_short | Integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity |
| title_sort | integrins and extracellular matrix proteins modulate adipocyte thermogenic capacity |
| url | https://doi.org/10.1038/s41598-021-84828-z |
| work_keys_str_mv | AT mariaagonzalezporras integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT katerinastojkova integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT marcellakvaicik integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT amandapelowe integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT annagoddi integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT alaniscarmona integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT byronlong integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT aminaaqutub integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT anjelicagonzalez integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT ronaldncohen integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity AT ericmbrey integrinsandextracellularmatrixproteinsmodulateadipocytethermogeniccapacity |