PMID- 32413985 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231103 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 9 IP - 5 DP - 2020 May 13 TI - Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases. LID - 10.3390/jcm9051446 [doi] LID - 1446 AB - Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer's disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 +/- 0.08 vs. 1.06 +/- 0.04 nmols O(2)/min; p = 0.024) and increased anaerobic metabolism (5.76 +/- 0.52 vs. 3.79 +/- 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (-12.13 +/- 21.86 vs. 199.22 +/- 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 +/- 82.77 vs. -69.55 +/- 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options. FAU - Catalan-Garcia, Marc AU - Catalan-Garcia M AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Garcia-Garcia, Francesc Josep AU - Garcia-Garcia FJ AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Moreno-Lozano, Pedro J AU - Moreno-Lozano PJ AUID- ORCID: 0000-0002-5501-5272 AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Alcarraz-Vizan, Gema AU - Alcarraz-Vizan G AD - Diabetes and Obesity Laboratory Research, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain. AD - CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, 28029 Madrid, Spain. FAU - Tort-Merino, Adria AU - Tort-Merino A AUID- ORCID: 0000-0002-5646-0482 AD - Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic and Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain. FAU - Milisenda, Jose Cesar AU - Milisenda JC AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Canto-Santos, Judith AU - Canto-Santos J AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Barcos-Rodriguez, Tamara AU - Barcos-Rodriguez T AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Cardellach, Francesc AU - Cardellach F AUID- ORCID: 0000-0003-3286-3436 AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Llado, Albert AU - Llado A AD - Alzheimer's Disease and Other Cognitive Disorders Unit, Hospital Clinic and Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain. FAU - Novials, Anna AU - Novials A AD - Diabetes and Obesity Laboratory Research, Institut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain. AD - CIBERDEM-Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, 28029 Madrid, Spain. FAU - Garrabou, Gloria AU - Garrabou G AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. FAU - Grau-Junyent, Josep M AU - Grau-Junyent JM AD - Muscle Research and Mitochondrial Function Laboratory, CELLEX-IDIBAPS, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain. AD - Internal Medicine Department, Hospital Clinic of Barcelona, 08036 Barcelona, Spain. AD - CIBERER-Spanish Biomedical Research Centre in Rare Diseases, 28029 Madrid, Spain. LA - eng GR - PIE14/00061/Integrated Projects of Excellence/ GR - PERIS SLT008/18/00061/CERCA programs from the Generalitat de Catalunya/ GR - PI1800498/Instituto de Salud Carlos III/ GR - PI1800451/Instituto de Salud Carlos III/ GR - 2017 SGR 893/Fundacion Cellex/ GR - PERIS SLT008/18/00061/Departament de Salut, Generalitat de Catalunya/ PT - Journal Article DEP - 20200513 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC7290779 OTO - NOTNLM OT - Alzheimer 2 OT - T2DM 3 OT - comorbidity 5 OT - mitochondria 4 OT - myositis 6 OT - sIBM 1 COIS- The authors declare no conflict of interest. EDAT- 2020/05/18 06:00 MHDA- 2020/05/18 06:01 PMCR- 2020/05/13 CRDT- 2020/05/17 06:00 PHST- 2020/03/31 00:00 [received] PHST- 2020/05/01 00:00 [revised] PHST- 2020/05/05 00:00 [accepted] PHST- 2020/05/17 06:00 [entrez] PHST- 2020/05/18 06:00 [pubmed] PHST- 2020/05/18 06:01 [medline] PHST- 2020/05/13 00:00 [pmc-release] AID - jcm9051446 [pii] AID - jcm-09-01446 [pii] AID - 10.3390/jcm9051446 [doi] PST - epublish SO - J Clin Med. 2020 May 13;9(5):1446. doi: 10.3390/jcm9051446.