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A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle
(Wiley, 2024-09-24) Díaz-Castro, Francisco; Tuñón-Suárez, Mauro; Rivera, Patricia; Botella, Javier; Cancino, Jorge; Figueroa, Ana María; Gutiérrez, Juan; Cantin, Claudette; Deldicque, Louise; Zbinden-Foncea, Hermann; Nielsen, Joachim; Henríquez-Olguín, Carlos; Morselli, Eugenia; Castro-Sepulveda, Mauricio
Aim The present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM). Methods Eight 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. Results Our 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. Conclusion The 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.
Association between adipose tissue characteristics and metabolic flexibility in humans: A systematic review
(Frontiers Media S.A., 2021-12-03) Glaves, Alice; Díaz-Castro, Francisco; Farías, Javiera; Ramírez-Romero, Rodrigo; Galgan, Jose E.; Fernández-Verdejo, Rodrigo
Adipose tissue total amount, distribution, and phenotype influence metabolic health. This may be partially mediated by the metabolic effects that these adipose tissue characteristics exert on the nearby and distant tissues. Thus, adipose tissue may influence the capacity of cells, tissues, and the organism to adapt fuel oxidation to fuel availability, i.e., their metabolic flexibility (MetF). Our aim was to systematically review the evidence for an association between adipose tissue characteristics and MetF in response to metabolic challenges in human adults. We searched in PubMed (last search on September 4, 2021) for reports that measured adipose tissue characteristics (total amount, distribution, and phenotype) and MetF in response to metabolic challenges (as a change in respiratory quotient) in humans aged 18 to <65 years. Any study design was considered, and the risk of bias was assessed with a checklist for randomized and non-randomized studies. From 880 records identified, 22 remained for the analysis, 10 of them measured MetF in response to glucose plus insulin stimulation, nine in response to dietary challenges, and four in response to other challenges. Our main findings were that: (a) MetF to glucose plus insulin stimulation seems inversely associated with adipose tissue total amount, waist circumference, and visceral adipose tissue; and (b) MetF to dietary challenges does not seem associated with adipose tissue total amount or distribution. In conclusion, evidence suggests that adipose tissue may directly or indirectly influence MetF to glucose plus insulin stimulation, an effect probably explained by skeletal muscle insulin sensitivity
BMAL1 and CLOCK proteins exhibit differential association with mitochondrial dynamics, protein synthesis pathways and muscle strength in human muscle
(The Physiological Society, 2024-06-26) Figueroa-Toledo, A. M.; Gutiérrez-Pino, J.; Carriel-Nesvara, A.; Marchese-Bittencourt, M.; Zbinden-Foncea, Hermann; Castro-Sepulveda, Mauricio
Murine models lacking CLOCK/BMAL1 proteins in skeletal muscle (SkM) present muscle deterioration and mitochondria abnormalities. It is unclear whether humans with lower levels of these proteins in the SkM have similar alterations. Here we evaluated the association between BMAL1 and CLOCK protein mass with mitochondrial dynamics parameters and molecular and functional SkM quality markers in males. SkM biopsies were taken from the vastus lateralis of 16 male (non-athletes, non-obese and non-diabetic) subjects (8–9 a.m.). The morphology of mitochondria and their interaction with the sarcoplasmic reticulum (mitochondria-SR) were determined using transmission electron microscopy images. Additionally, protein abundance of the OXPHOS complex, mitochondria fusion/fission regulators, mitophagy and signalling proteins related to muscle protein synthesis were measured. To evaluate the quality of SkM, the cross-sectional area and maximal SkM strength were also measured. The results showed that BMAL1 protein mass was positively associated with mitochondria-SR distance, mitochondria size, mitochondria cristae density and mTOR protein mass. On the other hand, CLOCK protein mass was negatively associated with mitochondria-SR interaction, but positively associated with mitochondria complex III, OPA1 and DRP1 protein mass. Furthermore, CLOCK protein mass was positively associated with the protein synthesis signalling pathway (total mTOR, AKT and P70S6K protein mass) and SkM strength. These findings suggest that the BMAL1 and CLOCK proteins play different roles in regulating mitochondrial dynamics and SkM function in males, and that modulation of these proteins could be a potential therapeutic target for treating muscle diseases.
Cholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic flux in skeletal muscle cells
(BMC, 2023-06-08) Abrigo, Johanna; Olguín, Hugo; Tacchi, Franco; Orozco-Aguilar, Josué; Valero, Mayalen; Soto, Jorge; Castro-Sepulveda, Mauricio; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, Claudio
Background Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. Methods We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. Results DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. Conclusion Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.
Concurrent training and interindividual response in women with a high number of metabolic syndrome risk factors
(Frontiers Media S.A., 2022-09-22) Delgado-Floody, Pedro; Chirosa-Ríos, Luis; Caamaño-Navarrete, Felipe; Valdés-Badilla, Pablo; Herrera-Valenzuela, Tomás; Monsalves-Álvarez, Matías; Núñez-Espinosa, Cristian; Castro-Sepulveda, Mauricio; Guzmán-Muñoz, Eduardo; Andrade, David C.; Álvarez, Cristian
The non-responders (NRs) after exercise training have been poorly studied in populations with morbid obesity. The purpose of this study was to determine the NR prevalence after 20 weeks of concurrent training of morbidly obese women with a high or low number of metabolic syndrome (MetS) risk factors. Twenty-eight women with morbid obesity participated in an exercise training intervention and were allocated into two groups distributed based on a high (≥3, n = 11) or low number (<3, n = 17) of MetS risk factors. The main outcomes were waist circumference (WC), fasting plasma glucose (FPG), high-density lipids (HDL-c), triglycerides (Tg), and systolic (SBP) and diastolic (DBP) blood pressure, and secondary outcomes were body composition, anthropometric and physical fitness, determined before and after 20 weeks of concurrent training. NRs were defined as previously used technical error cut-off points for the MetS outcomes. Significantly different (all p < 0.05) prevalences of NRs between the H-MetS vs. L-MetS groups (respectively) in WC (NRs 18.2 % vs. 41.1 %, p < 0.0001), SBP (NRs 72.7 % vs. 47.0 %, p = 0.022), DBP (NRs 54.5 % vs. 76.4 %, p < 0.0001), FPG (NRs 100% vs. 64.8 %, p < 0.0001), and HDL-c (NRs 90.9 % vs. 64.7 %, p = 0.012) were observed. In addition, the H-MetS group evidenced significant changes on ΔSBP (−10.2 ± 11.4 mmHg), ΔFPG (−5.8 ± 8.2 mg/dl), ΔHDL-c (+4.0 ± 5.9 mg/dl), and ΔTg (−8.8 ± 33.8 mg/dl), all p < 0.05. The L-MetS group only showed significant changes in ΔWC (−3.8 ± 5.0 cm, p = 0.009). Comparing H-MetS vs. L-MetS groups, significant differences were observed in ∆FPG (−5.8 ± 8.2 vs. +0.3 ± 3.2 mg/dl, p = 0.027), but not in other MetS outcomes. In conclusion, 20 weeks of concurrent training promotes greater beneficial effects in morbidly obese patients with a high number of MetS risk factors. However, the NR prevalence for improving MetS outcomes was significantly superior in these more-diseased groups in SBP, FPG, and HDL-c, independent of their major training-induced effects.
Creatine supplementation prior to strength exercise training is not superior in preventing muscle mass loss compared with standard nutritional recommendations in females after bariatric surgery: a pilot study
(Springer Nature, 2024) Díaz Pizarro, Marcelo; Pino Zúñiga, Johanna; Olivares Gálvez , Mariela; Rendón Vesga , Carolina; Luengas Tello, Rafael; Duque Seguro, Juan Camilo; Cancino, Jorge
Background: This study examines whether creatine supplementation combined with strength training mitigates muscle mass loss in women during early rehabilitation post-bariatric surgery, as its effectiveness remains untested in this context. Methods: Fifteen women (37.8 ± 9.6 years; BMI, 38.8 ± 5.6 kg/m2) completed the intervention (creatine group = 7; placebo group = 8). Both groups followed a strength training program three times a week for 8 weeks. The dosage for both the creatine and placebo was 8 g prior to each exercise session. Body weight, skeletal muscle mass, fat mass, handgrip strength, and physical activity levels were measured before and after the intervention. Results: The creatine group showed a reduction of 9.5 ± 1.5 kg in body weight, with a 0.72 ± 0.6 kg decrease in muscle mass and an 8.64 ± 1.2 kg reduction in fat mass. The placebo group had a reduction of 9.6 ± 3.5 kg in body weight, with a 0.6 ± 1.2 kg decrease in muscle mass and an 8.88 ± 3.2 kg reduction in fat mass, without significant differences between groups (p > 0.05). Conclusion: The pre-session strength exercise training creatine supplementation is not superior to placebo regarding body weight and fat mass losses and the attenuation of muscle mass loss during the first weeks of rehabilitation following bariatric surgery.
Detraining’s effects on cardiorespiratory fitness and maximal and explosive strength in army soldiers: does age matter?
(MDPI, 2024-07-01) Arce-Álvarez, Alexis; Zaio, Ángelo; Salazar-Ardiles, Camila; Álvarez, Cristian; Merino-Muñoz, Pablo; Vasquez-Muñoz, Manuel; Izquierdo, Mikel; Castro-Sepulveda, Mauricio; Andrade, David C.
Purpose: This study investigated the impact of four weeks of age-dependent detraining on army soldiers’ cardiorespiratory fitness and maximal and explosive strength. Methods: Fourteen volunteer tactical athletes participated, divided into two age groups (20 to 29 and 30 to 40 years). Before and after the detraining period, we assessed their anthropometric measurements (weight, height, body mass index, fat mass, and fat-free mass), cardiorespiratory fitness (maximal oxygen uptake [VO2max] and ventilatory thresholds [VT1 and VT2]), and kinematic properties during a single-leg counter-moving jump (CMJ) test for both the dominant and non-dominant legs. Two-way ANOVA followed by the Holm–Sidak post hoc test was used. Results: The anthropometric and cardiovascular variables did not show significant differences between the groups. However, both groups exhibited a significantly reduced maximum time and speed at the VO2max. Furthermore, the flight time and maximum height during the CMJ significantly decreased in the non-dominant leg for both age groups. Notably, the dominant leg’s concentric impulse (CI) significantly reduced during the CMJ, but this effect was observed only in the 30–40 age group. There were significant differences between the two age groups. Conclusions: Our findings suggest that four weeks of detraining negatively impacts aerobic fitness and muscular strength, independently of age. However, the dominant leg may be more susceptible to detraining effects in army soldiers aged 30–40. Furthermore, as a perspective, our results strongly suggest that a detraining period could affect successful missions (aerobic performance deterioration), as well as promote a muscle imbalance between the legs, which could encourage muscle injuries and endanger combat missions.
Early exercise through telerehabilitation after bariatric surgery: is it feasible?
(Springer, 2024) Pino Zúñiga, Johanna; Olivares, Mariela; Muñoz, Giselle; Boza, Camilo; Duque, Camilo; Cancino, Jorge
Purpose: The feasibility of early telerehabilitation after bariatric surgery is unknown. The objective of this study was to assess the feasibility and perception of engaging in the online exercise protocol in patients during the first month after bariatric surgery. Material and methods: A total of 67 patients, enrolled in a telerehabilitation program following bariatric surgery, completed a survey assessing their perception of the intensity, discomfort, and safety during exercise sessions. Results: Forty percent of participants began exercising between 5 and 10 days after surgery. Seventy-one percent of patients did not experience discomfort during the first month of exercise, and those who reported discomfort mainly mentioned dizziness and abdominal pain. No significant differences were found in the presence of discomfort among different types of surgeries performed. There was a significant difference in the presence of discomfort between patients who started exercising before and after 15 days of surgery, with less discomfort reported in the group that started after 15 days. Ninety-eight percent of patients felt safe during online exercise sessions. Most participants perceived the intensity of the sessions as moderate. The most frequently mentioned benefits of exercise were increased energy, mood, and feeling more active. Conclusion: Telerehabilitation conducted during the first month after bariatric surgery was feasible and well tolerated by patients, providing a safe alternative for those patients who face difficulties with in-person interventions.
Effect of supervised resistance training on arm volume, quality of life and physical perfomance among women at high risk for breast cancer-related Lymphedema: A study protocol for a randomized controlled Trial (STRONG-B)
(Frontiers Media S.A., 2022-03) Ramírez-Parada, Karol; Lopez-Garzon, Maria; Sanchez-Rojel, Cesar; Petric-Guajardo, Militza; Alfaro-Barra, Margarita; Fernández-Verdejo, Rodrigo; Reyes-Ponce, Alvaro; Merino-Pereira, Gina; Cantarero-Villanueva, Irene
Objectives: To determine the preventive effects of supervised resistance training on arms volume, quality of life, physical performance, and handgrip strength in Chilean women at high risk for breast cancer-related lymphedema (BCRL) undergoing chemotherapy. Design: Randomized control trial. Participants: One hundred and six women at high risk for breast cancer-related lymphedema aged 18 to 70 years. Interventions: Participants will be randomized into two groups: [a] intervention, who will receive 12 weeks of supervised resistance training (STRONG-B) during adjuvant chemotherapy; and [b] control, who will receive education to promote lymphatic and venous return, maintain range of motion, and promote physical activity. Main Outcome Measures: The primary outcome will be arms volume measured with an optoelectric device (perometer NT1000). Secondary outcomes will be quality of life, handgrip strength, and physical performance. Primary and secondary outcomes will be measured at baseline, just after the intervention, and 3 and 6 months after. Statistical analysis will be performed following intention-to-treat and per-protocol approaches. The treatment effect will be calculated using linear mixed models. Discussion: The STRONG-B will be a tailored supervised resistance training that attempts to prevent or mitigate BCRL in a population that, due to both intrinsic and extrinsic factors, will commonly suffer from BCRL.
Effects of an antioxidants cocktail on glucose metabolism at rest, during exercise, and during a glucose load in healthy young subjects
(Sociedad Chilena de Nutrición, Bromatología y Toxicología, 2023-12-15) Rodríguez, Ivan; Paez Espinosa, Enma Verónica; Zbinden-Foncea, Hermann; Echeverria, Francisca; Castro-Sepulveda, 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.
Effects of ketone bodies on energy expenditure, substrate utilization, and energy intake in humans
(American Society for Biochemistry and Molecular Biology, 2023-09-11) Fernández-Verdejo, Rodrigo; Mey, Jacob T.; Ravussin, Eric
Recientemente se ha prestado atención al potencial de los enfoques cetogénicos para regular el equilibrio energético, ya que las cetonas pueden influir tanto en el gasto como en la ingesta de energía. En esta revisión narrativa, resumimos la evidencia más relevante sobre el papel de la cetosis en el gasto de energía, la utilización de sustratos y la ingesta de energía en humanos. Consideramos diferentes estrategias para inducir la cetosis, como el ayuno, la manipulación dietética y las fuentes exógenas de cetonas. En general, la cetosis no tiene una influencia importante en el gasto energético, pero promueve un cambio en la utilización del sustrato hacia la oxidación de los cuerpos cetónicos. Las estrategias para inducir la cetosis mediante la reducción de la disponibilidad de carbohidratos en la dieta (p. ej., dietas cetogénicas) no influyen de forma independiente en la ingesta de energía, por lo que son igualmente efectivas para perder peso que las dietas con mayor contenido de carbohidratos. Por el contrario, la ingesta de triglicéridos de cadena media y ésteres de cetonas induce cetosis y parece aumentar el gasto energético y reducir la ingesta energética en el contexto de una alta disponibilidad de carbohidratos. Estas últimas estrategias conducen a una pérdida de peso ligeramente mayor. Desafortunadamente, distinguir los efectos de las diversas estrategias cetogénicasper se de los efectos de otras respuestas fisiológicas no es posible con los datos humanos disponibles. Se necesitan estudios hospitalarios altamente controlados que utilicen estrategias específicas para aislar los efectos independientes de las cetonas para abordar adecuadamente esta brecha de conocimiento.
Effects of school closure on lifestyle behaviours and health outcomes in children during the COVID-19 pandemic in Chile: A time-matched analysis
(Wiley; World Obesity Federation, 2024-10-08) Suárez-Reyes, Mónica; Fernández-Verdejo, Rodrigo; Quintiliano, Daiana; Pinheiro, Anna Cristina; Pizarro, Tito
Background The COVID-19 pandemic led to school closures, potentially impairing children's behaviours and health. We aimed to explore the effects of school closure on lifestyle behaviours (dietary habits, physical activity) and health outcomes (adiposity, fitness, self-esteem, self-concept) in children. Methods We measured 247 children before school closure (October–November 2019) and after school reopening (October–November 2021) (COVID-19 group). To distinguish the changes due to school closure from changes due to growth, we included 655 age-matched children with cross-sectional measurements in October–November 2019 (control group). The response of this group (i.e., differences between children with 2 years of difference) was considered the expected response to growth. Two-way ANOVA was used to test age-by-group interactions, indicating an effect of school closure. Results In 7-to-9-year-old children, the COVID-19 group had larger-than-expected decreases in physical activity (by 0.4 points), resulting in higher physical inactivity prevalence (by 19 percent points) at 9 years. This was accompanied by larger-than-expected increases in fat percentage (by 6.1 percent point). In 8-to-10-year-old children, the COVID-19 group had higher physical inactivity prevalence at 10 years (by 20 percent points). This was accompanied by larger-than-expected increases in fat percentage (by 8.3 percent points), z-score BMI (by 0.90 units), and waist circumference (by 6.1 cm). In 9-to-11-year-old children, the COVID-19 group had larger-than-expected decreases in physical activity (by 0.3 points) and increases in self-concept (by 0.2 points). The response in dietary habits, fitness, or self-esteem was not different between groups. Conclusion Overall, school closure negatively impacted physical activity and adiposity, particularly in the youngest children.
Elevated Risk of Overweight/Obesity-Related Markers and Low Muscular Fitness in Children Attending Public Schools in Chile
(MDPI, 2022) Suárez-Reyes, Mónica; Fernández-Verdejo, Rodrigo
In Chile, children of low socioeconomic status usually attend public schools and have few opportunities to engage in healthy behaviors. This may increase their risk of overweight/obesity and low muscular fitness. Therefore, we aimed to determine the association between the school type attended with overweight/obesity-related markers and the muscular fitness of children in Chile. We included 1410 children (6–13 years old) attending public, subsidized, or private schools. Overweight/obesity-related markers included BMI Z-scores, waist circumference, and body fat percentage. Muscular fitness assessment included handgrip strength and standing long jump. The odds ratios [95% CI] of overweight/obesity, elevated waist circumference, elevated body fat, low handgrip strength, and low standing long jump were compared between school types. Compared with boys attending public schools, those attending subsidized or private schools had lower odds ratios of low handgrip strength (0.63 [0.42–0.94] and 0.44 [0.25–0.78], respectively). Girls attending subsidized schools, compared with those in public schools, had lower odds of overweight/obesity (0.63 [0.44–0.90]) and of having low handgrip strength (0.51 [0.34–0.78]). Compared with girls in public schools, those attending private schools had lower odds (vs. public schools) of overweight/obesity (0.45 [0.28–0.74]), of having elevated body fat (0.53 [0.29–0.96]), and of having low standing long jump (0.41 [0.21–0.77]). The elevated risk of overweight/obesity-related markers and lower muscular fitness in children, particularly girls, attending public schools increase their current and future disease risk. This suggests that childhood socioeconomic status plays a central role in determining disease risk. Health-promoting interventions specifically focused on children from disadvantaged contexts are required.
Energy expenditure in humans: principles, methods, and changes throughout the life course
(Annual Reviews Inc., 2024-05-17) Fernández-Verdejo, Rodrigo
Humans require energy to sustain their daily activities throughout their lives. This narrative review aims to (a) summarize principles and methods for studying human energy expenditure, (b) discuss the main determinants of energy expenditure, and (c) discuss the changes in energy expenditure throughout the human life course. Total daily energy expenditure is mainly composed of resting energy expenditure, physical activity energy expenditure, and the thermic effect of food. Total daily energy expenditure and its components are estimated using variations of the indirect calorimetry method. The relative contributions of organs and tissues determine the energy expenditure under different physiological conditions. Evidence shows that energy expenditure varies along the human life course, at least in part due to changes in body composition, the mass and specific metabolic rate of organs and tissues, and levels of physical activity. This information is crucial to estimate human energy requirements for maintaining health throughout the life course.
Estimation of ventilatory thresholds during exercise using respiratory wearable sensors
(Springer Nature, 2024) Contreras-Briceño, Felipe; Cancino, Jorge; Espinoza-Ramírez, Maximiliano; Fernández, Gonzalo; Johnson, Vader; Hurtado, Daniel
Ventilatory thresholds (VTs) are key physiological parameters used to evaluate physical performance and determine aerobic and anaerobic transitions during exercise. Current assessment of these parameters requires ergospirometry, limiting evaluation to laboratory or clinical settings. In this work, we introduce a wearable respiratory system that continuously tracks breathing during exercise and estimates VTs during ramp tests. We validate the respiratory rate and VTs predictions in 17 healthy adults using ergospirometry analysis. In addition, we use the wearable system to evaluate VTs in 107 recreational athletes during ramp tests outside the laboratory and show that the mean population values agree with physiological variables traditionally used to exercise prescription. We envision that respiratory wearables can be useful in determining aerobic and anaerobic parameters with promising applications in health telemonitoring and human performance.
Exploring the sequential accumulation of metabolic syndrome components in adults
(Springer Nature, 2022) Fernández-Verdejo, Rodrigo; Galgani, Jose E.
The metabolic syndrome (MetS) is diagnosed upon the manifestation of ≥ 3 out of 5 specific components, regardless of their combination. The sequence through which these components accumulate may serve to identify underlying pathophysiological mechanisms and improve MetS treatment. We aimed to explore whether there is a more frequent sequence of accumulation of components in adults. The cross-sectional data of the National Health Survey of Chile 2016–2017 was analyzed. Subjects aged 18 to < 65 years, with body mass index ≥ 18.5 kg/m2, having all MetS components measured, and not under drug treatment were included (n = 1944, 60% women). MetS components were operationalized based on harmonized criteria: elevated waist circumference (≥ 91 cm for men, ≥ 83 cm for women), reduced high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL for men, < 50 mg/dL for women), elevated triglycerides (≥ 150 mg/dL), elevated blood pressure (≥ 130 mmHg for systolic, or ≥ 85 mmHg for diastolic), and elevated glycemia (≥ 100 mg/dL). Subjects were grouped according to the number of components. Then, the prevalence of the observed combinations was determined. In subjects with one component, the most prevalent was waist circumference (56.7%). In subjects with two, the most prevalent combination was waist circumference and HDL-C (50.8%), while in subjects with three components was waist circumference, HDL-C, and triglycerides (54.0%). Finally, in subjects with four, the most prevalent combination was waist circumference, HDL-C, triglycerides, and blood pressure (40.8%). This pattern suggests that the most frequent accumulation sequence starts with abdominal obesity, followed by dyslipidemia, elevated blood pressure, and ultimately, dysglycemia. The factors that determine the sequence remain to be determined.
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.
Fibro-adipogenic progenitors in physiological adipogenesis and intermuscular adipose tissue remodeling
(Elsevier; International Union of Biochemistry and Molecular Biology, 2024-06) Flores-Opazo, Marcelo; Kopinke, Daniel; Helmbacher, Françoise; Fernández-Verdejo, Rodrigo; Tuñón-Suárez, Mauro; Lynch, Gordon S.; Contreras, Osvaldo
Excessive accumulation of intermuscular adipose tissue (IMAT) is a common pathological feature in various metabolic and health conditions and can cause muscle atrophy, reduced function, inflammation, insulin resistance, cardiovascular issues, and unhealthy aging. Although IMAT results from fat accumulation in muscle, the mechanisms underlying its onset, development, cellular components, and functions remain unclear. IMAT levels are influenced by several factors, such as changes in the tissue environment, muscle type and origin, extent and duration of trauma, and persistent activation of fibro-adipogenic progenitors (FAPs). FAPs are a diverse and transcriptionally heterogeneous population of stromal cells essential for tissue maintenance, neuromuscular stability, and tissue regeneration. However, in cases of chronic inflammation and pathological conditions, FAPs expand and differentiate into adipocytes, resulting in the development of abnormal and ectopic IMAT. This review discusses the role of FAPs in adipogenesis and how they remodel IMAT. It highlights evidence supporting FAPs and FAP-derived adipocytes as constituents of IMAT, emphasizing their significance in adipose tissue maintenance and development, as well as their involvement in metabolic disorders, chronic pathologies and diseases. We also investigated the intricate molecular pathways and cell interactions governing FAP behavior, adipogenesis, and IMAT accumulation in chronic diseases and muscle deconditioning. Finally, we hypothesize that impaired cellular metabolic flexibility in dysfunctional muscles impacts FAPs, leading to IMAT. A deeper understanding of the biology of IMAT accumulation and the mechanisms regulating FAP behavior and fate are essential for the development of new therapeutic strategies for several debilitating conditions.
Gaps between the indication and the home execution of massage therapy in children in the postsurgical stage of primary cheiloplasty or rhinocheiloplasty
(Mutaz B. Habal, 2023-09) Montero-Orellana, María José; Fuentes-Orellana, María Rosa; Ossa-Cox, Matías
Purpose: This study describes the compliance rate with home massage therapy in children in the postsurgical stage of primary cheiloplasty or rhinocheiloplasty and the factors that facilitate or hinder its execution. Methods: The parents of 15 children treated at the Gantz Foundation - Children’s hospital for cleft lip and palate in Santiago, Chile were recruited. Parents received instructions to perform massages at home 5 times daily and were followed up for 3 months by recording in a log. Qualitative information on facilitators and barriers was collected in a focus group session. Results: Compliance rate was close to 75%, and the factors that facilitated the execution were performing the massage with some distracting activity and noticing the positive changes in the appearance of the scars. The most important factors that hindered the execution were the infant’s crying and changes in the routine. Conclusion: The authors conclude that the compliance rate is high and suggest that parents and guardians identify and implement a routine with a distracting activity that allows the massage to be carried out effectively.
Gasto energético en reposo y concentración sérica de lipoproteínas de baja densidad en adultos con hipotiroidismo subclínico leve
(Sociedad Chilena de Nutrición, Bromatología y Toxicología, 2024-04-01) Fernández-Verdejo, Rodrigo
La alta prevalencia de hipotiroidismo subclínico en Chile puede deberse a que el límite superior normal de la hormona estimulante del tiroides (TSH) sérica es bajo. Personas con TSH levemente mayor al límite superior pueden ser metabólicamente similares a personas sanas. Se compararon marcadores de acción tiroidea (gasto energético en reposo [GER] y lipoproteína de baja densidad [LDL]) en adultos con hipotiroidismo subclínico leve y con función tiroidea normal con o sin tratamiento con levotiroxina. Se midió GER, perfil lipídico y tiroideo en personas sanas con función tiroidea normal (TSH ≥0,4-<4,5 µUI/ml; n=91); con hipotiroidismo subclínico leve (TSH ≥4,5-≤6,5 µUI/ml; n=5); y con hipotiroidismo clínico tratado con levotiroxina y TSH normal (n=13). Se analizó la LDL en 838 personas sanas con función tiroidea normal y 89 con hipotiroidismo subclínico leve de la Encuesta Nacional de Salud 2016/17 (ENS). El GER, ajustado por peso, sexo y edad, fue similar entre grupos (p=0,71). La LDL fue similar entre personas con función tiroidea normal e hipotiroidismo subclínico leve (91±24 vs. 101±17 mg/dl; p=0,67), y menor en hipotiroidismo tratado (64±22 mg/dl; p<0,01). La LDL no se asoció con TSH pero si inversamente con T4L en mujeres (r=-0,33; p=0,02; n=53). En la ENS, ambos grupos tuvieron similar LDL (p=0,34), la que se asoció inversamente con T4L en mujeres (r=-0,12; p=0,01; n=569) pero no con TSH. Personas sanas con función tiroidea normal y con hipotiroidismo subclínico leve tienen similar GER y LDL. Esto apoya la idea de redefinir el límite superior normal de TSH.

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