miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset
Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-03-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121000147 |
| _version_ | 1818622449433968640 |
|---|---|
| author | Julia Sánchez-Ceinos Oriol A. Rangel-Zuñiga Mercedes Clemente-Postigo Alicia Podadera-Herreros Antonio Camargo Juan Francisco Alcalá-Diaz Rocío Guzmán-Ruiz José López-Miranda María M. Malagón |
| author_facet | Julia Sánchez-Ceinos Oriol A. Rangel-Zuñiga Mercedes Clemente-Postigo Alicia Podadera-Herreros Antonio Camargo Juan Francisco Alcalá-Diaz Rocío Guzmán-Ruiz José López-Miranda María M. Malagón |
| author_sort | Julia Sánchez-Ceinos |
| collection | DOAJ |
| description | Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of circulating miRNAs associated with T2D onset remains unexplored. Herein, we investigated the relationship between T2D-associated circulating miRNAs and AT function, as well as the role of preadipocytes and adipocytes as secreting cells of candidate circulating miRNAs. Among the plasma miRNAs related to T2D onset in the CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) cohort, baseline miR-223-3p levels (diminished in patients who next developed T2D [incident-T2D]) were significantly related to AT insulin resistance (IR). Baseline serum from incident-T2D participants induced inflammation and IR in 3T3-L1 adipocytes. We demonstrated that tumor necrosis factor (TNF)-α inhibited miR-223-3p secretion while enhancing miR-223-3p intracellular accumulation in 3T3-L1 (pre)adipocytes. Overexpression studies showed that an intracellular increase of miR-223-3p impaired glucose and lipid metabolism in these cells. Our findings provide mechanistic insights into the alteration of circulating miRNAs preceding T2D, unveiling both preadipocytes and adipocytes as miR-223-3p-secreting cells and suggesting that inflammation promotes miR-223-3p intracellular accumulation, which might contribute to (pre)adipocyte dysfunction and body metabolic dysregulation. |
| first_indexed | 2024-12-16T18:25:21Z |
| format | Article |
| id | doaj.art-c0954ca26d4f417b9dfce133aba48e13 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-16T18:25:21Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-c0954ca26d4f417b9dfce133aba48e132022-12-21T22:21:26ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-03-012310351052miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onsetJulia Sánchez-Ceinos0Oriol A. Rangel-Zuñiga1Mercedes Clemente-Postigo2Alicia Podadera-Herreros3Antonio Camargo4Juan Francisco Alcalá-Diaz5Rocío Guzmán-Ruiz6José López-Miranda7María M. Malagón8Department of Cell Biology, Physiology, and Immunology; Maimónides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital; Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain; Lipids and Atherosclerosis Unit; Department of Internal Medicine, IMIBIC/Reina Sofia University Hospital/University of Córdoba; Avda. Menéndez Pidal s/n, 14004, Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology; Maimónides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital; Avda. Menéndez Pidal s/n, 14004 Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology; Maimónides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital; Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain; Lipids and Atherosclerosis Unit; Department of Internal Medicine, IMIBIC/Reina Sofia University Hospital/University of Córdoba; Avda. Menéndez Pidal s/n, 14004, Córdoba, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain; Lipids and Atherosclerosis Unit; Department of Internal Medicine, IMIBIC/Reina Sofia University Hospital/University of Córdoba; Avda. Menéndez Pidal s/n, 14004, Córdoba, SpainDepartment of Cell Biology, Physiology, and Immunology; Maimónides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital; Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain; Lipids and Atherosclerosis Unit; Department of Internal Medicine, IMIBIC/Reina Sofia University Hospital/University of Córdoba; Avda. Menéndez Pidal s/n, 14004, Córdoba, Spain; Corresponding author: José López-Miranda, Lipids and Atherosclerosis Unit; Department of Internal Medicine, IMIBIC/Reina Sofia University Hospital/University of Córdoba, 14004-Córdoba, Spain.Department of Cell Biology, Physiology, and Immunology; Maimónides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital; Avda. Menéndez Pidal s/n, 14004 Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN); Instituto de Salud Carlos III (ISCIII), 28029, Madrid, Spain; Corresponding author: María M. Malagón, Department of Cell Biology, Physiology, and Immunology, IMIBIC/University of Córdoba/Reina Sofia University Hospital, 14004-Córdoba, Spain.Circulating microRNAs (miRNAs) have been proposed as biomarkers for type 2 diabetes (T2D). Adipose tissue (AT), for which dysfunction is widely associated with T2D development, has been reported as a major source of circulating miRNAs. However, the role of dysfunctional AT in the altered pattern of circulating miRNAs associated with T2D onset remains unexplored. Herein, we investigated the relationship between T2D-associated circulating miRNAs and AT function, as well as the role of preadipocytes and adipocytes as secreting cells of candidate circulating miRNAs. Among the plasma miRNAs related to T2D onset in the CORonary Diet Intervention with Olive oil and cardiovascular PREVention (CORDIOPREV) cohort, baseline miR-223-3p levels (diminished in patients who next developed T2D [incident-T2D]) were significantly related to AT insulin resistance (IR). Baseline serum from incident-T2D participants induced inflammation and IR in 3T3-L1 adipocytes. We demonstrated that tumor necrosis factor (TNF)-α inhibited miR-223-3p secretion while enhancing miR-223-3p intracellular accumulation in 3T3-L1 (pre)adipocytes. Overexpression studies showed that an intracellular increase of miR-223-3p impaired glucose and lipid metabolism in these cells. Our findings provide mechanistic insights into the alteration of circulating miRNAs preceding T2D, unveiling both preadipocytes and adipocytes as miR-223-3p-secreting cells and suggesting that inflammation promotes miR-223-3p intracellular accumulation, which might contribute to (pre)adipocyte dysfunction and body metabolic dysregulation.http://www.sciencedirect.com/science/article/pii/S2162253121000147adipose tissueadipocytecirculating microRNAsinflammationmiR-223-3ppreadipocytes |
| spellingShingle | Julia Sánchez-Ceinos Oriol A. Rangel-Zuñiga Mercedes Clemente-Postigo Alicia Podadera-Herreros Antonio Camargo Juan Francisco Alcalá-Diaz Rocío Guzmán-Ruiz José López-Miranda María M. Malagón miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset Molecular Therapy: Nucleic Acids adipose tissue adipocyte circulating microRNAs inflammation miR-223-3p preadipocytes |
| title | miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset |
| title_full | miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset |
| title_fullStr | miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset |
| title_full_unstemmed | miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset |
| title_short | miR-223-3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset |
| title_sort | mir 223 3p as a potential biomarker and player for adipose tissue dysfunction preceding type 2 diabetes onset |
| topic | adipose tissue adipocyte circulating microRNAs inflammation miR-223-3p preadipocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121000147 |
| work_keys_str_mv | AT juliasanchezceinos mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT oriolarangelzuniga mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT mercedesclementepostigo mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT aliciapodaderaherreros mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT antoniocamargo mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT juanfranciscoalcaladiaz mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT rocioguzmanruiz mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT joselopezmiranda mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset AT mariammalagon mir2233pasapotentialbiomarkerandplayerforadiposetissuedysfunctionprecedingtype2diabetesonset |