Examinando por Autor "Castro-Sepulveda, Mauricio"

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    Ítem
    The fasting-feeding metabolic transition regulates mitochondrial dynamics
    (Federation of American Society of Experimental Biology (FASEB), 2021-10-10) Castro-Sepulveda, Mauricio; Morio, Béatrice; Tuñón-Suárez, Mauro; Jannas-Vela, Sebastian; Díaz-Castro, Francisco; Rieusset, Jennifer; Zbinden-Foncea, Hermann
    In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca2+ exchange in the mitochondrial dynamic response to substrate availability. To determine whether PBMCs could be used in obesity context (low MetFlex), we measured mitochondrial dynamics in mouse spleen-derived lymphocytes from WT and ob/ob mice. We demonstrated that the transition from fasting to feeding reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs. In addition, we demonstrated that IP3R activity is key in the mitochondrial dynamics response when PBMCs are treated with a fasting-substrate in vitro. In murine mononuclear-cells, we confirmed that mitochondria-ER interactions are regulated in the fasted-fed transition and we further highlight mitochondria-ER miscommunication in PBMCs of diabetic mice. In conclusion, our results demonstrate that the fasting/feeding transition reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs, and that IP3R activity may potentially play a central role.
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    Low abundance of Mfn2 protein correlates with reduced mitochondria-SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images
    (Wiley Open Access, 2021-03-08) Castro-Sepulveda, Mauricio; Fernández-Verdejo, Rodrigo; Tuñón-Suárez, Mauro; Morales-Zúñiga, Jorge; Troncoso, Mayarling; Jannas-Vela, Sebastian; Zbinden-Foncea, Hermann
    The role of mitofusin 2 (Mfn2) in the regulation of skeletal muscle (SM) mitochondria-sarcoplasmic (SR) juxtaposition, mitochondrial morphology, mitochondrial cristae density (MCD), and SM quality has not been studied in humans. In in vitro studies, whether Mfn2 increases or decreases mitochondria-SR juxtaposition remains controversial. Transmission electron microscopy (TEM) images are commonly used to measure the organelle juxtaposition, but the measurements are performed "by-hand," thus potentially leading to between-rater differences. The purposes of this study were to: (1) examine the repeatability and reproducibility of mitochondrial-SR juxtaposition measurement from TEM images of human SM between three raters with different experience and (2) compare the mitochondrial-SR juxtaposition, mitochondrial morphology, MCD (stereological-method), and SM quality (cross-sectional area [CSA] and the maximum voluntary contraction [MVC]) between subjects with high abundance (Mfn2-HA; n = 6) and low abundance (Mfn2-LA; n = 6) of Mfn2 protein. The mitochondria-SR juxtaposition had moderate repeatability and reproducibility, with the most experienced raters showing the best values. There were no differences between Mfn2-HA and Mfn2-LA groups in mitochondrial size, distance from mitochondria to SR, CSA, or MVC. Nevertheless, the Mfn2-LA group showed lower mitochondria-SR interaction, MCD, and VO2max . In conclusion, mitochondrial-SR juxtaposition measurement depends on the experience of the rater, and Mfn2 protein seems to play a role in the metabolic control of human men SM, by regulating the mitochondria-SR interaction.
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    Microencapsulated pomegranate peel extract induces mitochondrial complex IV activity and prevents mitochondrial cristae alteration in brown adipose tissue in mice fed on a high-fat diet
    (Cambridge University Press, 2021-09-28) Echeverria, Francisca; Jimenez Patino, Paula; Castro-Sepulveda, Mauricio; Bustamante, Andres; Garcia Concha, Paula; Poblete-Aro, Carlos; Valenzuela, Rodrigo; Garcia-Diaz, Diego F.
    Pomegranate peel is an agro-industrial residue obtained after fruit processing with high total polyphenol (TP) content, making it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favouring mitochondrial biogenesis and function have also been described. However, once phenolic compounds are extracted, their stability can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation into functional foods. Nevertheless, studies on the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. This study aims to evaluate the effect of MPPE on brown adipose tissue (BAT) mitochondrial structure and function and metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a wall material and physically-chemically characterised. Eight-week-old male C57BL/6J mice (n 40) were randomly distributed into five groups: control diet (CD), HFD, HFD + IN, HFD + PPE (50 mg/kg per d TP) and HFD + MPPE (50 mg/kg per d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. Blood and adipose tissue samples were obtained. MPPE supplementation prevented HFD-induced body weight gain (P < 0·001), fasting glycaemia (P = 0·007) and total cholesterol rise (P = 0·001). MPPE resulted in higher BAT mitochondrial complex IV activity (P = 0·03) and prevented HFD-induced mitochondrial cristae alteration (P = 0·02). In conclusion, MPPE prevented HFD-induced excessive body weight gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae structure in BAT in mice fed with a HFD.
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    ¿Los niveles de Testosterona y Cortisol influyen en el rendimiento en el rugby?: una mirada al rugby sevens
    (Sociedad Chilena de Medicina del Deporte, 2022-04-30) Zúñiga-Vergara., Pedro; Castro-Sepulveda, Mauricio
    Resumen: Introducción: El Rugby 7 (R7) es una rama del Rugby Unión (RU) y se caracteriza principalmente por ser un deporte de oposición con períodos de juego intensos y de corta duración, por lo tanto, los componentes psicológicos y fisiológicos juegan un rol en el rendimiento. En el R7, los deportistas compiten varias veces durante un mismo día, permitiendo la acumulación de fatiga. Esta acumulación de fatiga se puede explicar principalmente por la intensidad del juego y el número de colisiones a alta intensidad provocando perturbaciones a nivel muscular, endocrino y del sistema inmune. Sin embargo, a la fecha no existen trabajos que integren las respuestas fisiológicas como, por ejemplo, las respuestas hormonales de los jugadores a dichas demandas. Objetivo: Realizar una revisión de la literatura científica en relación al efecto de las hormonas T, C y el Ratio T/C en el rendimiento deportivo en el R7. Metodología: Revisión narrativa de la literatuta, se realizó una búsqueda durante los meses de abril a noviembre del 2021 en 4 bases de datos (Pubmed/Medline, Google Scholar, Scopus (Elsevier) y Scielo). Después de analizar 335 textos se consideró su utilidad y relevacia para la inclusión a esta revisión. 11 Estudios cumplierón con los criterios de inclusión. Resultados: Los trabajos incluidos asocián la relación hormonal con el rendimiento deportivo en el RU y R7. Se destaca la relación grande (r=0,80) de la T con el rendimiento deportivo en el RU. Conclusión: Según los estudios analizados se puede observar
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    Severe COVID-19 correlates with lower mitochondrial cristae density in PBMCs and greater sitting time in humans
    (Wiley; The Physiological Society and the American Physiological Society, 2022-05-27) Castro-Sepulveda, Mauricio; Tapia, German; Tuñón-Suárez, Mauro; Marambio, Hugo; Valero-Breton, Mayalen; Fernández-Verdejo, Rodrigo; Zbinden-Foncea, Hermann
    An interaction between mitochondrial dynamics, physical activity levels, andCOVID-19 severity has been previously hypothesized. However, this has notbeen tested. We aimed to compare mitochondrial morphology and cristae den-sity of PBMCs between subjects with non- severe COVID- 19, subjects with se-vere COVID- 19, and healthy controls. Additionally, we compared the level ofmoderate-vigorous physical activity (MVPA) and sitting time between groups.Blood samples were taken to obtain PBMCs. Mitochondrial dynamics were as-sessed by electron microscopy images and western blot of protein that regulatemitochondrial dynamics. The International Physical Activity Questionnaire(IPAQ; short version) was used to estimate the level of MVPA and the sitting timeThe patients who develop severe COVID-19 (COVID-19++) not present altera-tions of mitochondrial size neither mitochondrial density in comparison to non-severe patients COVID- 19 (COVID- 19) and control subjects (CTRL). However,compared to CTRL, COVID- 19 and COVID-19++ groups have lower mitochon-drial cristae length, a higher proportion of abnormal mitochondrial cristae. TheCOVID-19++ group has lower number (trend) and length of mitochondrial cris-tae in comparison to COVID- 19 group. COVID- 19, but not COVID- 19++ grouphad lower Opa 1, Mfn 2 and SDHB (Complex II) proteins than CTRL group.Besides, COVID-19++ group has a higher time sitting. Our results show that lowmitochondrial cristae density, potentially due to physical inactivity, is associatedwith COVID-19 severity.