Nutrition, bioenergetics, and metabolic syndrome

According to the World Health Organization (WHO), the global nutrition report shows that whilst part of the world's population starves, the other part suffers from obesity and associated complications. A balanced diet counterparts these extreme conditions with the proper proportion, composition, quantity, and presence of macronutrients, micronutrients, and bioactive compounds. However, little is known on the way these components exert any influence on our health. These nutrients aiming to feed our bodies, our tissues, and our cells, first need to reach mitochondria, where they are decomposed into CO2 and H2O to obtain energy. Mitochondria are the powerhouse of the cell and mainly responsible for nutrients metabolism, but they are also the main source of oxidative stress and cell death by apoptosis. Unappropriated nutrients may support mitochondrial to become the Trojan horse in the cell. This review aims to provide an approach to the role that some nutrients exert on mitochondria as a major contributor to high prevalent Western conditions including metabolic syndrome (MetS), a constellation of pathologic conditions which promotes type II diabetes and cardiovascular risk. Clinical and experimental data extracted from in vitro animal and cell models further demonstrated in patients, support the idea that a balanced diet, in a healthy lifestyle context, promotes proper bioenergetic and mitochondrial function, becoming the best medicine to prevent the onset and progression of MetS. Any advance in the prevention and management of these prevalent complications help to face these challenging global health problems, by ameliorating the quality of life of patients and reducing the associated sociosanitary burden

Medicina interna y enfermedades raras. Transición niño-adulto

Most rare diseases (RD) are genetically based, occur with very different symptoms and may cause a different degree of disability, especially inborn errors of metabolism (IEM). The clinical transition process of a patient with a RD reaching adulthood aims to ensure uninterrupted, coordinated and psychologically-appropriate health care through multidisciplinary expert units (EU). The specialist in Internal Medicine has a central role, along with Nutrition and Dietetics, a specialized ECM laboratory, and other specialists (Neurology, Clinical Genetics, Pharmacy, Ophthalmology, Obstetrics, Psychiatry, Nursing, Social Work, with the support of pediatricians experienced in ECM). EU should organize the overall care, develop clinical guidelines for diagnosis, follow-up and treatment, adapt Pharmacy services, create patient registers, establish relationships with patients’ associations, develop a scientific training program, establish international partnerships, facilitate collaboration with the Pharmaceutical Industry and have its own research activity.La mayoría de las enfermedades raras (ER) son de base genética, cursan con síntomas muy diversos y a menudo ocasionan un grado variable de discapacidad, especialmente los errores congénitos del metabolismo (ECM). El proceso de transición clínica de un paciente con una ER que alcanza la edad adulta pretende garantizar una atención sanitaria ininterrumpida, coordinada y psicológicamente apropiada mediante unidades expertas (UE) multidisciplinares. El especialista en medicina interna tiene un papel central, junto a los de nutrición y dietética, laboratorio especializado en ECM y otros especialistas (neurología, genética clínica, farmacia, oftalmología, obstetricia, psiquiatría, enfermería, trabajo social, con el apoyo de pediatría experimentada en ECM). Las UE deberían organizar la asistencia, desarrollar guías clínicas de diagnóstico, seguimiento y tratamiento, adaptar los servicios de farmacia, crear un registro de pacientes, establecer relaciones con las asociaciones de pacientes, desarrollar un programa científico formativo, establecer colaboraciones internacionales, facilitar la colaboración con la industria farmacéutica y mantener una actividad investigadora propia

Comment on Yeste et al.: Polyphenols and IUGR Pregnancies: Intrauterine Growth Restriction and Hydroxytyrosol Affect the Development and Neurotransmitter Profile of the Hippocampus in a Pig Model

Intrauterine growth restriction (IUGR) affects 5-10% of newborns and increases the risks of intrauterine demise, neonatal morbidity, and death. In their recent publication, Yeste et al. found the benefits of hydroxytyrosol supplementation on brain remodeling from an IUGR pig model. Additionally, we found a significant decrease in phenolic alcohol (tyrosol and hydroxytyrosol) intake in IUGR pregnant women. Altogether, these findings support the notion that dietetic interventions, through supplementation but mostly via a balanced diet, can ameliorate IUGR complications. Furthermore, diet intervention combined with early biomarkers may allow clinicians to eventually anticipate IUGR diagnosis and help avoid one of the most frequent causes of newborn mortality and morbidity

Neuronal induction and bioenergetics characterization of human forearm adipose stem cells from Parkinson's disease patients and healthy controls

Neurodegenerative diseases, such as Parkinson's disease, are heterogeneous disorders with a multifactorial nature involving impaired bioenergetics. Stem-regenerative medicine and bioenergetics have been proposed as promising therapeutic targets in the neurologic field. The rationale of the present study was to assess the potential of human-derived adipose stem cells (hASCs) to transdifferentiate into neuronal-like cells (NhASCs and neurospheres) and explore the hASC bioenergetic profile. hASC neuronal transdifferentiation was performed through neurobasal media and differentiation factor exposure. High resolution respirometry was assessed. Increased MAP-2 neuronal marker protein expression upon neuronal induction (p<0.05 undifferentiated hASCs vs. 28-36 days of differentiation) and increased bIII-tubulin neuronal marker protein expression upon neuronal induction (p<0.05 undifferentiated hASCs vs. 6-28-36 days of differentiation) were found. The bioenergetic profile was detectable through high-resolution respirometry approaches in hASCs but did not lead to differential oxidative capacity rates in healthy or clinically diagnosed PD-hASCs. We confirmed the capability of transdifferentiation to the neuronal-like profile of hASCs derived from the forearms of human subjects and characterized the bioenergetic profile. Suboptimal maximal respiratory capacity trends in PD were found. Neuronal induction leading to positive neuronal protein expression markers is a relevant issue that encourages the suitability of NhASC models in neurodegeneration

Mitochondrial dysfunction: a common hallmark underlying comorbidity between sIBM and other degenerative and age-related diseases

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 O2/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