Browsing by Author "Zbinden-Foncea, Hermann"

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    A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle
    (2024) Diaz-Castro, Francisco; Tunon-Suarez, Mauro; Rivera, Patricia; Botella, Javier; Cancino, Jorge; Figueroa, Ana Maria; Gutierrez, Juan; Cantin, Claudette; Deldicque, Louise; Zbinden-Foncea, Hermann; Nielsen, Joachim; Henriquez-Olguin, Carlos; Morselli, Eugenia; Castro-Sepulveda, Mauricio
    AimThe present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM).MethodsEight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex-leg). Mitophagy was assessed using protein-related abundance, transmission electron microscopy (TEM), and fluorescence microscopy.ResultsOur results show that acute resistance exercise increased pro-fission protein phosphorylation (DRP1Ser616) and decreased mitophagy markers such as PARKIN and BNIP3L/NIX protein abundance in the Ex-leg. Additionally, mitochondrial complex IV decreased in the Ex-leg when compared to the Rest-leg. In the Ex-leg, TEM and immunofluorescence images showed mitochondrial cristae abnormalities, a mitochondrial fission phenotype, and increased mitophagosome-like structures in both subsarcolemmal and intermyofibrillar mitochondria. We also observed increased mitophagosome-like structures on the subsarcolemmal cleft and mitochondria in the extracellular space of SkM in the Ex-leg. We stimulated human primary myotubes with CCCP, which mimics mitophagy induction in the Ex-leg, and found that BNIP3L/NIX protein abundance decreased independently of lysosomal degradation. Finally, in another human cohort, we found a negative association between BNIP3L/NIX protein abundance with both mitophagosome-like structures and mitochondrial cristae density in the SkM.ConclusionThe findings suggest that a single bout of resistance exercise can initiate mitophagy, potentially involving mitochondrial ejection, in human skeletal muscle. BNIP3L/NIX is proposed as a sensitive marker for assessing mitophagy flux in SkM.
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    Cardiorespiratory fitness and fat oxidation during exercise as protective factors for insulin resistance in sedentary women with overweight or obesity
    (2018) Cancino-Ramirez, Javiera; Soto-Sanchez, Johana; Zbinden-Foncea, Hermann; Moreno González, Manuel I.; Leyton-Dinamarca, Barbara; Gonzalez-Rojas, Luis
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    Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects
    (2023) Rodríguez, Iván; Paez Espinosa, Enma Verónica; Zbinden-Foncea, Hermann; EcheverrÍa González, Francisca Cecilia; Castro-Sepúlveda, Mauricio
    Background: Reactive oxygen species (ROS) regulate glucose metabolism (GM) in skeletal muscle by improving the translocation of GLUT4. Antioxidant supplementation could block this physiological effect, altering glucose signaling during exercise. However, there is limited evidence in humans on whether antioxidant intake affects GM. Therefore, we aimed to determine the effect of an antioxidant cocktail (AOC) on GM at rest and during metabolic challenges. Methods: Ten healthy male subjects received AOC supplementation (1000 mg of Vitamin C, 600 IU of Vitamin E, and 600 mg of α-lipoic acid) or placebo (2.000 mg of talc) before two trials conducted 7 days apart. Trial 1: AOC 120 and 90 minutes before an endurance exercise (EEX) bout at 60 % of maximal oxygen uptake (VO2max ); Trial 2: AOC 120 and 90 minutes before an oral glucose tolerance test (OGTT; 75 g glucose). Measurements of gas exchange and capillary blood samples were collected every 15 minutes during both trials. Results: AOC supplementation increased resting glucose levels (p<0.05). During Trial 1 (EEX), the AOC increased carbohydrate oxidation (CHOox) (p= 0.03), without effect in glucose blood levels. During Trial 2 (OGTT), the AOC supplementation had no significant effect on GM parameters. Conclusion: Acute supplementation with AOC increased resting glucose levels and CHOox during EEX in healthy subjects, with no effect on GM during the OGTT. Keywords: α-lipoic acid; Glucose metabolism; Substrate oxidation; Vitamin C, Vitamin E.
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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
    (2021) Castro-Sepulveda, Mauricio; Fernandez-Verdejo, Rodrigo; Tunon-Suarez, Mauro; Morales-Zuniga, 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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    The fasting-feeding metabolic transition regulates mitochondrial dynamics
    (2021) Castro-Sepulveda, Mauricio; Morio, Beatrice; Tunon-Suarez, Mauro; Jannas-Vela, Sebastian; Diaz-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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    Time reallocation of physical behaviours induced by endurance exercise in physically active individuals
    (2023) Hayes-Ortiz, Thomas; Suarez-Reyes, Monica; Galgani Fuentes, José Eduardo; Zbinden-Foncea, Hermann; Fernandez-Verdejo, Rodrigo
    Increasing moderate-vigorous physical activity (MVPA) through exercise requires reallocating time from other physical behaviour(s). We aimed to determine the reallocations induced by endurance exercise in physically active individuals. We also searched for behavioural compensatory responses, and explored the effect of exercise on daily energy expenditure. Fourteen participants (8 women; median age 37.8 [IQR 29.9-48.5] yr) exercised on Monday, Wednesday, and Friday mornings (cycling MVPA, 65 min/session; "exercise days"), and avoided exercising on Tuesday and Thursday ("rest days"). Time spent on sleep, sedentary behaviour, light-intensity physical activity, and MVPA was determined each day by accelerometers and logs. An energy expenditure index was computed considering minutes spent on each behaviour and fixed metabolic equivalents. We found that all participants had lower sleep and higher total (including exercise) MVPA on exercise days compared to rest days. Thus, on exercise vs. rest days, sleep was lower (490 [453-553] vs. 553 [497-599] min/day, respectively, P < 0.001), and total MVPA was higher (86 [80-101] vs. 23 [15-45] min/day, respectively; P < 0.001). No differences in other physical behaviours were detected. Notably, exercise not only induced reallocations (i.e. less time in other behaviours) but also behavioural compensatory responses in some participants (e.g. increased sedentary behaviour). This rearrangement of physical behaviours manifested in exercise-induced increases in energy expenditure from 96 to 232 MET x min/day. In conclusion, active individuals reallocated time from sleep to accommodate morning exercise. Yet exercise induced variable rearrangements of behaviours, with some individuals manifesting compensatory responses. Understanding individual rearrangements may help improve exercise interventions.