Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance
Low-grade chronic inflammation plays a pivotal role in the pathogenesis of insulin resistance (IR), and skeletal muscle has a central role in this condition. NLRP3 inflammasome activation pathways promote low-grade chronic inflammation in several tissues. However, a direct link between IR and NLRP3...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/19/10212 |
| _version_ | 1797516393392898048 |
|---|---|
| author | Luan Américo-Da-Silva Javiera Aguilera Oscar Quinteros-Waltemath Pablo Sánchez-Aguilera Javier Russell Cynthia Cadagan Roberto Meneses-Valdés Gina Sánchez Manuel Estrada Gonzalo Jorquera Genaro Barrientos Paola Llanos |
| author_facet | Luan Américo-Da-Silva Javiera Aguilera Oscar Quinteros-Waltemath Pablo Sánchez-Aguilera Javier Russell Cynthia Cadagan Roberto Meneses-Valdés Gina Sánchez Manuel Estrada Gonzalo Jorquera Genaro Barrientos Paola Llanos |
| author_sort | Luan Américo-Da-Silva |
| collection | DOAJ |
| description | Low-grade chronic inflammation plays a pivotal role in the pathogenesis of insulin resistance (IR), and skeletal muscle has a central role in this condition. NLRP3 inflammasome activation pathways promote low-grade chronic inflammation in several tissues. However, a direct link between IR and NLRP3 inflammasome activation in skeletal muscle has not been reported. Here, we evaluated the NLRP3 inflammasome components and their role in GLUT4 translocation impairment in skeletal muscle during IR. Male C57BL/6J mice were fed with a normal control diet (NCD) or high-fat diet (HFD) for 8 weeks. The protein levels of NLRP3, ASC, caspase-1, gasdermin-D (GSDMD), and interleukin (IL)-1β were measured in both homogenized and isolated fibers from the flexor digitorum brevis (FDB) or soleus muscle. GLUT4 translocation was determined through GLUT4<i>myc</i>-eGFP electroporation of the FBD muscle. Our results, obtained using immunofluorescence, showed that adult skeletal muscle expresses the inflammasome components. In the FDB and soleus muscles, homogenates from HFD-fed mice, we found increased protein levels of NLRP3 and ASC, higher activation of caspase-1, and elevated IL-1β in its mature form, compared to NCD-fed mice. Moreover, GSDMD, a protein that mediates IL-1β secretion, was found to be increased in HFD-fed-mice muscles. Interestingly, MCC950, a specific pharmacological NLRP3 inflammasome inhibitor, promoted GLUT4 translocation in fibers isolated from the FDB muscle of NCD- and HFD-fed mice. In conclusion, we found increased NLRP3 inflammasome components in adult skeletal muscle of obese insulin-resistant animals, which might contribute to the low-grade chronic metabolic inflammation of skeletal muscle and IR development. |
| first_indexed | 2024-03-10T07:00:35Z |
| format | Article |
| id | doaj.art-275775cab45147039b7961052c85f3a0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:35Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-275775cab45147039b7961052c85f3a02023-11-22T16:06:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191021210.3390/ijms221910212Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin ResistanceLuan Américo-Da-Silva0Javiera Aguilera1Oscar Quinteros-Waltemath2Pablo Sánchez-Aguilera3Javier Russell4Cynthia Cadagan5Roberto Meneses-Valdés6Gina Sánchez7Manuel Estrada8Gonzalo Jorquera9Genaro Barrientos10Paola Llanos11Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago 8380544, ChileInstituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago 8380544, ChileInstituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago 8380544, ChileCentro de Estudios en Ejercicio, Metabolismo y Cáncer, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileEscuela de Pedagogía en Educación Física, Facultad de Educación, Universidad Autónoma de Chile, Santiago 8900000, ChileInstituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago 8380544, ChileCentro de Estudios en Ejercicio, Metabolismo y Cáncer, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChilePrograma de Fisiopatología, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChilePrograma de Fisiología y Biofísica, ICBM, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileCentro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, ChileCentro de Estudios en Ejercicio, Metabolismo y Cáncer, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileInstituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago 8380544, ChileLow-grade chronic inflammation plays a pivotal role in the pathogenesis of insulin resistance (IR), and skeletal muscle has a central role in this condition. NLRP3 inflammasome activation pathways promote low-grade chronic inflammation in several tissues. However, a direct link between IR and NLRP3 inflammasome activation in skeletal muscle has not been reported. Here, we evaluated the NLRP3 inflammasome components and their role in GLUT4 translocation impairment in skeletal muscle during IR. Male C57BL/6J mice were fed with a normal control diet (NCD) or high-fat diet (HFD) for 8 weeks. The protein levels of NLRP3, ASC, caspase-1, gasdermin-D (GSDMD), and interleukin (IL)-1β were measured in both homogenized and isolated fibers from the flexor digitorum brevis (FDB) or soleus muscle. GLUT4 translocation was determined through GLUT4<i>myc</i>-eGFP electroporation of the FBD muscle. Our results, obtained using immunofluorescence, showed that adult skeletal muscle expresses the inflammasome components. In the FDB and soleus muscles, homogenates from HFD-fed mice, we found increased protein levels of NLRP3 and ASC, higher activation of caspase-1, and elevated IL-1β in its mature form, compared to NCD-fed mice. Moreover, GSDMD, a protein that mediates IL-1β secretion, was found to be increased in HFD-fed-mice muscles. Interestingly, MCC950, a specific pharmacological NLRP3 inflammasome inhibitor, promoted GLUT4 translocation in fibers isolated from the FDB muscle of NCD- and HFD-fed mice. In conclusion, we found increased NLRP3 inflammasome components in adult skeletal muscle of obese insulin-resistant animals, which might contribute to the low-grade chronic metabolic inflammation of skeletal muscle and IR development.https://www.mdpi.com/1422-0067/22/19/10212high-fat dietmyokinescaspase-1GSDMDNALP3inflammation |
| spellingShingle | Luan Américo-Da-Silva Javiera Aguilera Oscar Quinteros-Waltemath Pablo Sánchez-Aguilera Javier Russell Cynthia Cadagan Roberto Meneses-Valdés Gina Sánchez Manuel Estrada Gonzalo Jorquera Genaro Barrientos Paola Llanos Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance International Journal of Molecular Sciences high-fat diet myokines caspase-1 GSDMD NALP3 inflammation |
| title | Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance |
| title_full | Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance |
| title_fullStr | Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance |
| title_full_unstemmed | Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance |
| title_short | Activation of the NLRP3 Inflammasome Increases the IL-1β Level and Decreases GLUT4 Translocation in Skeletal Muscle during Insulin Resistance |
| title_sort | activation of the nlrp3 inflammasome increases the il 1β level and decreases glut4 translocation in skeletal muscle during insulin resistance |
| topic | high-fat diet myokines caspase-1 GSDMD NALP3 inflammation |
| url | https://www.mdpi.com/1422-0067/22/19/10212 |
| work_keys_str_mv | AT luanamericodasilva activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT javieraaguilera activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT oscarquinteroswaltemath activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT pablosanchezaguilera activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT javierrussell activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT cynthiacadagan activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT robertomenesesvaldes activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT ginasanchez activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT manuelestrada activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT gonzalojorquera activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT genarobarrientos activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance AT paolallanos activationofthenlrp3inflammasomeincreasestheil1blevelanddecreasesglut4translocationinskeletalmuscleduringinsulinresistance |