Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet
Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell lin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/15/5225 |
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| author | Paloma Lillo Urzúa Olinda Núñez Murillo Mauricio Castro-Sepúlveda María A. Torres-Quintana Álvaro Lladser Caldera Andrew F. G. Quest Carolina Espinoza Robles Paola Llanos Vidal Sergio Wehinger |
| author_facet | Paloma Lillo Urzúa Olinda Núñez Murillo Mauricio Castro-Sepúlveda María A. Torres-Quintana Álvaro Lladser Caldera Andrew F. G. Quest Carolina Espinoza Robles Paola Llanos Vidal Sergio Wehinger |
| author_sort | Paloma Lillo Urzúa |
| collection | DOAJ |
| description | Elevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-out (CAV1 KO) mice subjected to a high fat diet (HFD) should suffer less damage to beta cells than wild type (WT) mice. Here, we evaluated the in vivo response of beta cells in the pancreatic islets of 8-week-old C57Bl/6J CAV1 KO mice subjected to a control diet (CD, 14% kcal fat) or a HFD (60% kcal fat) for 12 weeks. We observed that CAV1 KO mice were resistant to weight gain when on HFD, although they had high serum cholesterol and FFA levels, impaired glucose tolerance and were insulin resistant. Some of these alterations were also observed in mice on CD. Interestingly, KO mice fed with HFD showed an adaptive response of the pancreatic beta cells and exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice. These in vivo results suggest that although the CAV1 KO mice are metabolically unhealthy, they adapt better to a HFD than WT mice. To shed light on the possible signaling pathway(s) involved, MIN6 murine beta cells expressing (MIN6 CAV) or not expressing (MIN6 Mock) CAV1 were incubated with the saturated fatty acid palmitate in the presence of mitogen-activated protein kinase inhibitors. Western blot analysis revealed that CAV1 enhanced palmitate-induced JNK, p38 and ERK phosphorylation in MIN6 CAV1 cells. Moreover, all the MAPK inhibitors partially restored MIN6 viability, but the effect was most notable with the ERK inhibitor. In conclusion, our results suggest that CAV1 KO mice adapted better to a HFD despite their altered metabolic state and that this may at least in part be due to reduced beta cell damage. Moreover, they indicate that the ability of CAV1 to increase sensitivity to FFAs may be mediated by MAPK and particularly ERK activation. |
| first_indexed | 2024-03-10T18:15:20Z |
| format | Article |
| id | doaj.art-b9dc68a03f644b55b91f2838ed44bcae |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:15:20Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b9dc68a03f644b55b91f2838ed44bcae2023-11-20T07:44:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-07-012115522510.3390/ijms21155225Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat DietPaloma Lillo Urzúa0Olinda Núñez Murillo1Mauricio Castro-Sepúlveda2María A. Torres-Quintana3Álvaro Lladser Caldera4Andrew F. G. Quest5Carolina Espinoza Robles6Paola Llanos Vidal7Sergio Wehinger8Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago 8370146, ChileEscuela de Microbiología, Universidad Nacional Autónoma de Honduras, Tegucigalpa 11101, HondurasEscuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago 7501015, ChileDepartamento de Patología y Medicina Oral, Facultad de Odontología, Universidad de Chile, Santiago 8380491, ChileLaboratory of Immunoncology, Fundación Ciencia & Vida, Santiago 7780272, ChileLaboratory of Cellular Communication, Program of Cell and Molecular Biology, Faculty of Medicine, Center for studies on Exercise, Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), University of Chile, Santiago 8380453, ChileThrombosis Research Center, Medical Technology School, Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, Talca 3460000, ChileInstitute for Research in Dental Sciences, Facultad de Odontología, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Universidad de Chile, Santiago 8380544, ChileThrombosis Research Center, Center for Studies on Exercise, Metabolism and Cancer (CEMC), Medical Technology School, Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Universidad de Talca, Talca 3481118, ChileElevated free fatty acids (FFAs) impair beta cell function and reduce beta cell mass as a consequence of the lipotoxicity that occurs in type 2 diabetes (T2D). We previously reported that the membrane protein caveolin-1 (CAV1) sensitizes to palmitate-induced apoptosis in the beta pancreatic cell line MIN6. Thus, our hypothesis was that CAV1 knock-out (CAV1 KO) mice subjected to a high fat diet (HFD) should suffer less damage to beta cells than wild type (WT) mice. Here, we evaluated the in vivo response of beta cells in the pancreatic islets of 8-week-old C57Bl/6J CAV1 KO mice subjected to a control diet (CD, 14% kcal fat) or a HFD (60% kcal fat) for 12 weeks. We observed that CAV1 KO mice were resistant to weight gain when on HFD, although they had high serum cholesterol and FFA levels, impaired glucose tolerance and were insulin resistant. Some of these alterations were also observed in mice on CD. Interestingly, KO mice fed with HFD showed an adaptive response of the pancreatic beta cells and exhibited a significant decrease in beta cell apoptosis in their islets compared to WT mice. These in vivo results suggest that although the CAV1 KO mice are metabolically unhealthy, they adapt better to a HFD than WT mice. To shed light on the possible signaling pathway(s) involved, MIN6 murine beta cells expressing (MIN6 CAV) or not expressing (MIN6 Mock) CAV1 were incubated with the saturated fatty acid palmitate in the presence of mitogen-activated protein kinase inhibitors. Western blot analysis revealed that CAV1 enhanced palmitate-induced JNK, p38 and ERK phosphorylation in MIN6 CAV1 cells. Moreover, all the MAPK inhibitors partially restored MIN6 viability, but the effect was most notable with the ERK inhibitor. In conclusion, our results suggest that CAV1 KO mice adapted better to a HFD despite their altered metabolic state and that this may at least in part be due to reduced beta cell damage. Moreover, they indicate that the ability of CAV1 to increase sensitivity to FFAs may be mediated by MAPK and particularly ERK activation.https://www.mdpi.com/1422-0067/21/15/5225ERK activitycaveolin-1high fat dietinsulin resistancediabetes |
| spellingShingle | Paloma Lillo Urzúa Olinda Núñez Murillo Mauricio Castro-Sepúlveda María A. Torres-Quintana Álvaro Lladser Caldera Andrew F. G. Quest Carolina Espinoza Robles Paola Llanos Vidal Sergio Wehinger Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet International Journal of Molecular Sciences ERK activity caveolin-1 high fat diet insulin resistance diabetes |
| title | Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet |
| title_full | Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet |
| title_fullStr | Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet |
| title_full_unstemmed | Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet |
| title_short | Loss of Caveolin-1 Is Associated with a Decrease in Beta Cell Death in Mice on a High Fat Diet |
| title_sort | loss of caveolin 1 is associated with a decrease in beta cell death in mice on a high fat diet |
| topic | ERK activity caveolin-1 high fat diet insulin resistance diabetes |
| url | https://www.mdpi.com/1422-0067/21/15/5225 |
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