Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy
LMNA mutation is associated with type-2 familial partial lipodystrophy (<i>FPLD2</i>). The disease causes a disorder characterized by anomalous accumulation of body fat in humans. The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism....
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Cristina Algieri Chiara Bernardini Fabiana Trombetti Elisa Schena Augusta Zannoni Monica Forni Salvatore Nesci |
| author_facet | Cristina Algieri Chiara Bernardini Fabiana Trombetti Elisa Schena Augusta Zannoni Monica Forni Salvatore Nesci |
| author_sort | Cristina Algieri |
| collection | DOAJ |
| description | LMNA mutation is associated with type-2 familial partial lipodystrophy (<i>FPLD2</i>). The disease causes a disorder characterized by anomalous accumulation of body fat in humans. The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism. In human fibroblasts and preadipocytes, a trend for ATP production, mainly supported by mitochondrial oxidative metabolism, is detected. Moreover, primary cell lines with <i>FPLD2</i> mutation decrease the mitochondrial ATP production if compared with the <i>control</i>, even if no differences are observed in the oxygen consumption rate of bioenergetic parameters (i.e., basal and maximal respiration, spare respiratory capacity, and ATP turnover). Conversely, glycolysis is only inhibited in <i>FPLD2</i> fibroblast cell lines. We notice that the amount of ATP produced in the fibroblasts is higher than in the preadipocytes, and likewise in the <i>control</i>, with respect to <i>FPLD2</i>, due to a more active oxidative phosphorylation (OXPHOS) and glycolysis. Moreover, the proton leak parameter, which characterizes the transformation of white adipose tissue to brown/beige adipose tissue, is unaffected by <i>FPLD2</i> mutation. The metabolic profile of fibroblasts and preadipocytes is confirmed by the ability of these cell lines to increase the metabolic potential of both OXPHOS and glycolysis under energy required independently by the <i>FPLD2</i> mutation. |
| first_indexed | 2024-03-09T12:31:02Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:31:02Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ba0b70d6f9544e51978bc55c476fb81c2023-11-30T22:30:04ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012315865910.3390/ijms23158659Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial LipodystrophyCristina Algieri0Chiara Bernardini1Fabiana Trombetti2Elisa Schena3Augusta Zannoni4Monica Forni5Salvatore Nesci6Department of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyCNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Unit of Bologna, 40126 Bologna, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyDepartment of Veterinary Medical Sciences, University of Bologna, 40064 Ozzano Emilia, ItalyLMNA mutation is associated with type-2 familial partial lipodystrophy (<i>FPLD2</i>). The disease causes a disorder characterized by anomalous accumulation of body fat in humans. The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism. In human fibroblasts and preadipocytes, a trend for ATP production, mainly supported by mitochondrial oxidative metabolism, is detected. Moreover, primary cell lines with <i>FPLD2</i> mutation decrease the mitochondrial ATP production if compared with the <i>control</i>, even if no differences are observed in the oxygen consumption rate of bioenergetic parameters (i.e., basal and maximal respiration, spare respiratory capacity, and ATP turnover). Conversely, glycolysis is only inhibited in <i>FPLD2</i> fibroblast cell lines. We notice that the amount of ATP produced in the fibroblasts is higher than in the preadipocytes, and likewise in the <i>control</i>, with respect to <i>FPLD2</i>, due to a more active oxidative phosphorylation (OXPHOS) and glycolysis. Moreover, the proton leak parameter, which characterizes the transformation of white adipose tissue to brown/beige adipose tissue, is unaffected by <i>FPLD2</i> mutation. The metabolic profile of fibroblasts and preadipocytes is confirmed by the ability of these cell lines to increase the metabolic potential of both OXPHOS and glycolysis under energy required independently by the <i>FPLD2</i> mutation.https://www.mdpi.com/1422-0067/23/15/8659mitochondrial oxidative metabolismglycolysistype-2 familial partial lipodystrophyATP productionfibroblastspre-adipocytes |
| spellingShingle | Cristina Algieri Chiara Bernardini Fabiana Trombetti Elisa Schena Augusta Zannoni Monica Forni Salvatore Nesci Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy International Journal of Molecular Sciences mitochondrial oxidative metabolism glycolysis type-2 familial partial lipodystrophy ATP production fibroblasts pre-adipocytes |
| title | Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy |
| title_full | Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy |
| title_fullStr | Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy |
| title_full_unstemmed | Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy |
| title_short | Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy |
| title_sort | cellular metabolism and bioenergetic function in human fibroblasts and preadipocytes of type 2 familial partial lipodystrophy |
| topic | mitochondrial oxidative metabolism glycolysis type-2 familial partial lipodystrophy ATP production fibroblasts pre-adipocytes |
| url | https://www.mdpi.com/1422-0067/23/15/8659 |
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