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It is unclear how skeletal muscle metabolism and mitochondrial function adapt to long duration bed rest and whether changes can be prevented by nutritional intervention. The present study aimed (1) to assess the effect of prolonged bed rest on skeletal muscle mitochondrial function and dynamics and (2) to determine whether micronutrient supplementation would mitigate the adverse metabolic effect of bed rest. Participants were maintained in energy balance throughout 60 days of bed rest with micronutrient supplementation (INT) (body mass index: 23.747 ± 1.877 kg m-2 ; 34.80 ± 7.451 years; n = 10) or without (control) (body mass index: 24.087 ± 2.088 kg m-2 ; 33.50 ± 8.541 years; n = 10). Indirect calorimetry and dual-energy x-ray absorptiometry were used for measures of energy expenditure, exercise capacity and body composition. Mitochondrial respiration was determined by high-resolution respirometry in permeabilized muscle fibre bundles from vastus lateralis biopsies. Protein and mRNA analysis further examined the metabolic changes relating to regulators of mitochondrial dynamics induced by bed rest. INT was not sufficient in preserving whole body metabolic changes conducive of a decrease in body mass, fat-free mass and exercise capacity within both groups. Mitochondrial respiration, OPA1 and Drp1 protein expression decreased with bed rest, with an increase pDrp1s616 . This reduction in mitochondrial respiration was explained through an observed decrease in mitochondrial content (mtDNA:nDNA). Changes in regulators of mitochondrial dynamics indicate an increase in mitochondrial fission driven by a decrease in inner mitochondrial membrane fusion (OPA1) and increased pDrp1s616 . KEY POINTS: Sixty days of -6° head down tilt bed rest leads to significant changes in body composition, exercise capacity and whole-body substrate metabolism. Micronutrient supplementation throughout bed rest did not preserve whole body metabolic changes. Bed rest results in a decrease in skeletal muscle mitochondrial respiratory capacity, mainly as a result of an observed decrease in mitochondrial content. Prolonged bed rest ensues changes in key regulators of mitochondrial dynamics. OPA1 and Drp1 are significantly reduced, with an increase in pDrp1s616 following bed rest indicative of an increase in mitochondrial fission. Given the reduction in mitochondrial content following 60 days of bed rest, the maintenance of regulators of mitophagy in line with the increase in regulators of mitochondrial fission may act to maintain mitochondrial respiration to meet energy demands.
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Muscle atrophy is a deleterious consequence of physical inactivity and is associated with increased morbidity and mortality. The aim of this study was to decipher the mechanisms involved in disuse muscle atrophy in eight healthy men using a 21 day bed rest with a cross-over design (control, with resistive vibration exercise (RVE), or RVE combined with whey protein supplementation and an alkaline salt (NEX)). The main physiological findings show a significant reduction in whole-body fat-free mass (CON -4.1%, RVE -4.3%, NEX -2.7%, p < 0.05), maximal oxygen consumption (CON -20.5%, RVE -6.46%, NEX -7.9%, p < 0.05), and maximal voluntary contraction (CON -15%, RVE -12%, and NEX -9.5%, p < 0.05) and a reduction in mitochondrial enzyme activity (CON -30.7%, RVE -31.3%, NEX -17%, p < 0.05). The benefits of nutrition and exercise countermeasure were evident with an increase in leg lean mass (CON -1.7%, RVE +8.9%, NEX +15%, p < 0.05). Changes to the vastus lateralis muscle proteome were characterized using mass spectrometry-based label-free quantitative proteomics, the findings of which suggest alterations to cell metabolism, mitochondrial metabolism, protein synthesis, and degradation pathways during bed rest. The observed changes were partially mitigated during RVE, but there were no significant pathway changes during the NEX trial. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD006882. In conclusion, resistive vibration exercise, when combined with whey/alkalizing salt supplementation, could be an effective strategy to prevent skeletal muscle protein changes, muscle atrophy, and insulin sensitivity during medium duration bed rest.
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Reposo en Cama , Vibración , Reposo en Cama/efectos adversos , Estudios Cruzados , Suplementos Dietéticos , Humanos , Masculino , Músculo Esquelético , Proteoma , Suero Lácteo , Proteína de Suero de LecheRESUMEN
Individuals that are capable of accumulating appropriate fat stores are assumed to have selective advantages when food becomes scarce. Similarly to species from temperate zones, some species inhabiting arid areas accumulate fat stores prior to periods of food limitation. Yet, we have little knowledge concerning seasonal variation in body composition and the relationship between fat store size and disappearance risk in species from arid habitats. Using the water dilution method, we examined the body composition of African striped mice (Rhabdomys pumilio) living in a seasonal habitat with a long food-restricted dry season. We tested for seasonal changes in body composition (N=159 measurements of 113 individuals) and whether dry season survival was related to fat mass (N=66 individuals). Fat stores were similar in size at the onset and the end of the dry season, but surprisingly smaller at the onset of the moist breeding season. Fat stores showed a negative relationship with food availability. Individual variation in fat stores was not associated with disappearance risk, but there was a positive association of disappearance risk with body mass. Increased disappearance risk of heavy individuals suggests elevated dispersal rates in competitive individuals. This study suggests that non-breeding philopatric striped mice do not accumulate large fat stores prior to the food-limited dry season but that they might mobilize fat stores at the onset of the breeding season to satisfy the energetic demands of reproduction and/or to decrease costs associated with larger fat stores, such as increased predation risk.
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Composición Corporal , Conducta Alimentaria , Longevidad , Murinae/fisiología , Reproducción , Adiposidad , Animales , Femenino , Masculino , Estado de Hidratación del Organismo , Estaciones del Año , Sudáfrica , AguaRESUMEN
Parasites affect many aspects of host physiology and behavior, and thus are generally thought to negatively impact host fitness. However, changes in form of short-term parasite effects on host physiological markers have generally been overlooked in favor of fitness measures. Here, we studied flea (Oropsylla idahoensis and Oropsylla opisocroistis tuberculata) parasitism on a natural population of Columbian ground squirrels (Urocitellus columbianus) in Sheep River Provincial Park, AB, Canada. Fleas were experimentally added to adult female U. columbianus at physiologically demanding times, including birth, lactation and weaning of their young. The body mass of adult females, as well as their oxidative stress and immunity were recorded multiple times over the active season under flea-augmented and control conditions. We also measured the prevalence of an internal parasite (Trypanosoma otospermophili). Doubly labeled water (DLW) was intra-peritoneally injected at peak lactation to examine energy expenditure. Effects of parasites on oxidative stress were only observed after offspring were weaned. There was no direct effect of experimentally heightened flea prevalence on energy use. A short-term 24â h mass loss (-17â g) was detected briefly after parasite addition, likely due to U. columbianus preferentially allocating time for grooming. Our parasite augmentation did not strongly affect hosts and suggested that short-term physiological effects were unlikely to culminate in long-term fitness consequences. Columbian ground squirrels appear to rapidly manage parasite costs, probably through grooming.
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Metabolismo Energético , Infestaciones por Pulgas/veterinaria , Interacciones Huésped-Parásitos/fisiología , Enfermedades de los Roedores/parasitología , Sciuridae , Alberta , Animales , Infestaciones por Pulgas/parasitología , Siphonaptera/fisiologíaRESUMEN
Animals living in seasonal environments must adapt to a wide variation of temperature changes which requires flexible adjustments of time budget and metabolic processes for efficient thermoregulation. The Japanese macaque (Macaca fuscata) is one of only a handful of nonhuman primate species that experience seasonal climates over a wide temperature range. We used behavior observations, accelerometer sensors and the doubly-labelled water (DLW) method to measure activity and total daily energy expenditure (TDEE) of M. fuscata housed in captivity but exposed to natural seasonal variations at day lengths ranging from 10 to 12â¯h and temperature ranging from 0° to 32°C. Although overall activity was significantly lower in winter compared to summer and autumn, we found no effect of temperature on day-time activity. However nocturnal inactivity and mean length of sleeping bouts significantly increased along a gradient of decreasing temperatures from summer through winter, suggesting the importance of adaptive behavioral thermoregulation in this species. Energy expenditure that was unaccounted for by Basal Metabolic Rate (BMR) and physical activity i.e. expended through diet-induced thermogenesis or thermoregulation was between 14% and 32%. This residual energy expenditure differed between summer/autumn and winter and was relatively consistent across individuals (approximately 5-8% higher in winter). The percentage of body fat and residual energy expenditure were negatively correlated, supporting that fat storage was higher when less energy was required for thermoregulation. Our results suggest that physiological mechanisms like behavioral and autonomic thermoregulation enable M. fuscata to adapt to wide fluctuations in environmental conditions which provide insights into the evolutionary adaptations of nonhuman primates in seasonal climate.
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Aclimatación , Metabolismo Energético , Macaca/metabolismo , Estaciones del Año , Animales , Regulación de la Temperatura Corporal , Peso Corporal , Femenino , Masculino , TemperaturaRESUMEN
BACKGROUND: Dispersal is often associated with a suite of phenotypic traits that might reduce dispersal costs, but can be energetically costly themselves outside dispersal. Hence, dispersing and philopatric individuals might differ throughout their life cycle in their management of energy production. Because higher energy expenditure can lead to the production of highly reactive oxidative molecules that are deleterious to the organism if left uncontrolled, dispersing and philopatric individuals might differ in their management of oxidative balance. Here, we experimentally increased flight costs during reproduction via a wing load manipulation in female collared flycatchers (Ficedula albicollis) breeding in a patchy population. We measured the effects of the manipulation on plasmatic markers of oxidative balance and reproductive success in dispersing and philopatric females. RESULTS: The impact of the wing load manipulation on the oxidative balance differed according to dispersal status. The concentration of reactive oxygen metabolites (ROMs), a marker of pro-oxidant status, was higher in philopatric than dispersing females in the manipulated group only. Differences between dispersing and philopatric individuals also depended on habitat quality, as measured by local breeding density. In low quality habitats, ROMs as well as nestling body mass were higher in philopatric females compared to dispersing ones. Independently of the manipulation or of habitat quality, plasma antioxidant capacity differed according to dispersal status: philopatric females showed higher antioxidant capacity than dispersing ones. Nestlings raised by philopatric females also had a higher fledging success. CONCLUSIONS: Our results suggest that dispersing individuals maintain a stable oxidative balance when facing challenging environmental conditions, at the cost of lower reproductive success. Conversely, philopatric individuals increase their effort, and thus oxidative costs, in challenging conditions thereby maintaining their reproductive success. Our study sheds light on energetics and oxidative balance as possible processes underlying phenotypic differences between dispersing and philopatric individuals.
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Distribución Animal , Especies Reactivas de Oxígeno/metabolismo , Pájaros Cantores/fisiología , Animales , Femenino , Estadios del Ciclo de Vida , ReproducciónRESUMEN
Bedrest shifts fasting and postprandial fuel selection towards carbohydrate use over lipids, potentially affecting astronauts' performance and health. We investigated whether this change occurs in astronauts after at least 3 months onboard the International Space Station (ISS). We further explored the associations with diet, physical activity (PA), and body composition. Before and during spaceflight, respiratory quotient (RQ), carbohydrate, and fat oxidation were measured by indirect calorimetry before and following a standardized meal in 11 males (age = 45.7 [SD 7.7] years, BMI = 24.3 [2.1] kg m-²). Postprandial substrate use was determined by 0-to-260 min postprandial incremental area under the curve (iAUC) of nutrient oxidation and the difference between maximal postprandial and fasting RQ (ΔRQ). Food quotient (FQ) was calculated from diet logs. Fat (FM) and fat-free mass (FFM) were measured by hydrometry and PA by accelerometry and diary logs. Spaceflight increased fasting RQ (P = 0.01) and carbohydrate oxidation (P = 0.04) and decreased fasting lipid oxidation (P < 0.01). An increase in FQ (P < 0.001) indicated dietary modifications onboard the ISS. Spaceflight-induced RQ changes adjusted for ground RQ correlated with inflight FQ (P < 0.01). In postprandial conditions, nutrient oxidation and ΔRQ were unaffected on average. Lipid oxidation changes negatively correlated with FFM changes and inflight aerobic exercise and positively with FM changes. The opposite was observed for carbohydrate oxidation. ΔRQ changes were negatively and positively related to FM and FFM changes, respectively. In conclusion, fasting substrate oxidation shift observed during spaceflight may primarily result from dietary modifications. Between-astronaut variability in postprandial substrate oxidation depends on body composition changes and inflight PA.
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Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss. Each of these adaptations could turn to serious health deterioration during the long-term spaceflight needed for planetary exploration. We hypothesized that resveratrol (RES), a natural polyphenol, could be used as a nutritional countermeasure to prevent muscle metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment maintained a net protein balance, soleus muscle mass, and soleus muscle maximal force contraction. RES also fully maintained soleus mitochondrial capacity to oxidize palmitoyl-carnitine and reversed the decrease of the glutathione vs. glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular level, the protein content of Sirt-1 and COXIV in soleus muscle was also preserved. RES further protected whole-body insulin sensitivity and lipid trafficking and oxidation, and this was likely associated with the maintained expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in muscle. Finally, chronic RES supplementation maintained the bone mineral density and strength of the femur. For the first time, we report a simple countermeasure that prevents the deleterious adaptations of the major physiological functions affected by mechanical unloading. RES could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.
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Inhibidores Enzimáticos/farmacología , Suspensión Trasera , Condicionamiento Físico Animal , Estilbenos/farmacología , Tejido Adiposo/metabolismo , Animales , Disponibilidad Biológica , Biomarcadores/sangre , Regulación de la Temperatura Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Inflamación/metabolismo , Resistencia a la Insulina , Masculino , Músculo Esquelético/efectos de los fármacos , Atrofia Muscular/tratamiento farmacológico , Ratas , Ratas Wistar , Resveratrol , Estilbenos/metabolismo , Estilbenos/farmacocinética , Estilbenos/orinaRESUMEN
OBJECTIVE: Body mass (BM) loss and body composition (BC) changes threaten astronauts' health and mission success. However, the energetic contribution of the exercise countermeasure to these changes has never been investigated during long-term missions. We studied energy balance and BC in astronauts during 6-month missions onboard the International Space Station. METHODS: Before and after at least 3 months in space, BM, BC, total and activity energy expenditure (TEE and AEE) were measured using the doubly labeled water method in 11 astronauts (2011-2017). Physical activity (PA) was assessed by the SensewearPro® activity-device. RESULTS: Three-month spaceflight decreased BM (- 1.20 kg [SE 0.5]; P = 0.04), mainly due to non-significant fat-free mass loss (FFM; - 0.94 kg [0.59]). The decrease in walking time (- 63.2 min/day [11.5]; P < 0.001) from preflight was compensated by increases in non-ambulatory activities (+ 64.8 min/day [18.8]; P < 0.01). Average TEE was unaffected but a large interindividual variability was noted. Astronauts were stratified into those who maintained (stable_TEE; n = 6) and those who decreased (decreased_TEE; n = 5) TEE and AEE compared to preflight data. Although both groups lost similar BM, FFM was maintained and FM reduced in stable_TEE astronauts, while FFM decreased and FM increased in decreased_TEE astronauts (estimated between-group-difference (EGD) in ΔFFMindex [FFMI] 0.87 kg/m2, 95% CI + 0.32 to + 1.41; P = 0.01, ΔFMindex [FMI] - 1.09 kg/m2, 95% CI - 2.06 to - 0.11 kg/m2; P = 0.03). The stable_TEE group had higher baseline FFMI, and greater baseline and inflight vigorous PA than the decreased_TEE group (P < 0.05 for all). ΔFMI and ΔFFMI were respectively negatively and positively associated with both ΔTEE and ΔAEE. CONCLUSION: Both ground fitness and inflight overall PA are associated with spaceflight-induced TEE and BC changes and thus energy requirements. New instruments are needed to measure real-time individual changes in inflight energy balance components.
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Astronautas , Composición Corporal , Humanos , Metabolismo Energético , Ejercicio FísicoRESUMEN
BACKGROUND: Fasting is attracting an increasing interest as a potential strategy for managing diseases, including metabolic disorders and complementary cancer therapy. Despite concerns of clinicians regarding protein catabolism and muscle loss, evidence-based clinical data in response to long-term fasting in healthy humans are scarce. The objective of this study was to measure clinical constants, metabolic, and muscular response in healthy men during and after a 10 day fast combined with a physical activity programme. METHODS: Sixteen men (44 ± 14 years; 26.2 ± 0.9 kg/m2 ) fasted with a supplement of 200-250 kcal/day and up to 3 h daily low-intensity physical activity according to the peer-reviewed Buchinger Wilhelmi protocol. Changes in body weight (BW) and composition, basal metabolic rate (BMR), physical activity, muscle strength and function, protein utilization, inflammatory, and metabolic status were assessed during the 10 day fast, the 4 days of food reintroduction, and at 3 month follow-up. RESULTS: The 10 day fast decreased BW by 7% (-5.9 ± 0.2 kg, P < 0.001) and BMR by 12% (P < 0.01). Fat mass and lean soft tissues (LST) accounted for about 40% and 60% of weight loss, respectively, -2.3 ± 0.18 kg and -3.53 ± 0.13 kg, P < 0.001. LST loss was explained by the reduction in extracellular water (44%), muscle and liver glycogen and associated water (14%), and metabolic active lean tissue (42%). Plasma 3-methyl-histidine increased until Day 5 of fasting and then decreased, suggesting that protein sparing might follow early proteolysis. Daily steps count increased by 60% (P < 0.001) during the fasting period. Strength was maintained in non-weight-bearing muscles and increased in weight-bearing muscles (+33%, P < 0.001). Glycaemia, insulinemia, blood lipids, and blood pressure dropped during the fast (P < 0.05 for all), while non-esterified fatty acids and urinary beta-hydroxybutyrate increased (P < 0.01 for both). After a transient reduction, inflammatory cytokines returned to baseline at Day 10 of fasting, and LST were still lower than baseline values (-2.3% and -3.2%, respectively; P < 0.05 for both). CONCLUSIONS: A 10 day fast appears safe in healthy humans. Protein loss occurs in early fast but decreases as ketogenesis increases. Fasting combined with physical activity does not negatively impact muscle function. Future studies will need to confirm these first findings.
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Adaptación Fisiológica , Ayuno , Adulto , Ejercicio Físico , Humanos , Masculino , Persona de Mediana Edad , Músculos , Estudios ProspectivosRESUMEN
This study investigated the extent to which the increase in torpor expression in the grey mouse lemur, due to graded food restriction, is modulated by a trade-off between a whole body sparing of polyunsaturated dietary fatty acids and the related oxidative stress generated during daily torpor. We measured changes in torpor frequency, total energy expenditure (TEE), linoleate (polyunsaturated fatty acid) and palmitate (saturated fatty acid) oxidation, hexanoyl-lysine (HEL; the product of linoleate peroxidation), and 8-hydroxydeoxyguanosine (8OHdG; a marker of DNA damage). Animals under summer-acclimated long days (LD) or winter-acclimated short days (SD) were exposed to a 40% (LD40 and SD40) and 80% (LD80 and SD80) 35-day calorie restriction (CR). During CR, all groups reduced their body mass, but LD80 animals reached survival-threatened levels at day 22 and were then excluded from the CR trial. Only SD mouse lemurs increased their torpor frequency with CR and displayed a decrease in their TEE adjusted for fat-free mass. After CR, SD40 mouse lemurs shifted the dietary fatty acid oxidation toward palmitate and spared linoleate. Such a shift was not observed in LD animals and during severe CR, during which oxidation of both dietary fatty acids was increased. Concomitantly, HEL increased in both LD40 and SD80 groups, whereas DNA damage was only seen in SD80 food-restricted animals. HEL correlated positively with linoleate oxidation confirming in vivo the substrate/product relationship demonstrated in vitro, and negatively with TEE adjusted for fat-free mass, suggesting higher oxidative stress associated with increased torpor expression. This suggests a seasonal-dependant, cost-benefit trade-off between maximizing torpor propensity and minimizing oxidative stress that is associated with a shift toward sparing of dietary polyunsaturated fatty acids that is dependent upon the expression of a winter phenotype.
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Cheirogaleidae/metabolismo , Daño del ADN , Grasas de la Dieta/metabolismo , Privación de Alimentos , Hibernación , Ácido Linoleico/metabolismo , Estrés Oxidativo , Ácido Palmítico/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Biomarcadores/metabolismo , Peso Corporal , Restricción Calórica , Cheirogaleidae/genética , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , Metabolismo Energético , Lisina/análogos & derivados , Lisina/metabolismo , Masculino , Oxidación-Reducción , Fenotipo , Fotoperiodo , Estaciones del AñoRESUMEN
In many species, males follow alternative reproductive tactics (ARTs), where one tactic (called bourgeois) has much higher reproductive success than alternative tactics followed by males with lower competitive ability. The extent to which ARTs differ in energetic costs is unknown, but it is important to understand the fitness payoffs of ARTs. We studied male African striped mice (Rhabdomys pumilio) which follow one of three ARTs: heavy bourgeois males defend harems of females and have 10 times higher reproductive success than smaller roamers, which have ten times higher reproductive success than philopatric males, which remain in their natal group and are the smallest males. Bourgeois and philopatric males live in social groups that defend one territory, while roamers are solitary and roam over larger areas. We predicted that roamers will face higher energetic costs compared to group-living males because they do not gain thermoregulatory benefits of huddling in groups and might travel larger distances as they have larger home ranges. We measured daily energy expenditure (DEE) of 30 males, resting metabolic rate (RMR) of 79 males, travel distances and daily ranges of 31 males and changes in body mass of 51 males. Roamers had higher DEE and higher RMR than both types of group-living males. Philopatric males had shorter travel distances and smaller daily ranges than both roamers and bourgeois males, which did not differ from each other. This indicates that the higher DEE of roamers compared to bourgeois males cannot be explained by larger travel distances. Philopatrics gained body mass faster than bourgeois males and roamers, thereby increasing their competitive ability and thus the probability of later switching to a tactic of higher reproductive success. Our results suggest that roamers suffer energetic costs that might reduce their ability of gaining body mass and thus the likelihood of switching to the bourgeois tactic, indicating evolutionary trade-offs between investing energy into roaming versus gaining body mass.
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Metabolismo Energético/fisiología , Reproducción/fisiología , Conducta Sexual Animal/fisiología , Conducta Social , Animales , Peso Corporal/fisiología , Masculino , MurinaeRESUMEN
Agriculture intensification, marked by the generalization of crop monoculture, by the increase in plot size and by the reduction of plant diversity, has led to huge decline in wildlife in European farmlands. In such habitat, research has long been biased towards birds and invertebrates, while very few studies have investigated the effect on small mammals. Considering the European hamster, Cricetus cricetus, we therefore review the different techniques that can be used to investigate the impact of environmental changes and conservation measures in small and endangered wild mammals. We suggest that only a multidisciplinary approach will allow exploration of these effects, combining experimental laboratory work on captive-bred animals with the monitoring of wild individuals. In particular, individual energy balance has to be investigated and measured as accurately as possible, through either biochemical or bio-logging techniques. It is, indeed, the most affected physiological trait in a changing environment, as it determines both the reproductive output and the survival of the individual. We also discuss the inconvenience of capture-release approaches for such an endangered species and emphasize the disturbance that experimental protocols could impose on the hamster.
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Conservación de los Recursos Naturales/métodos , Cricetinae/fisiología , Especies en Peligro de Extinción , Animales , Animales Salvajes , Dinámica PoblacionalRESUMEN
Physical inactivity and sedentary behaviors are independent risk factors for numerous diseases. We examined the ability of a nutrient cocktail composed of polyphenols, omega-3 fatty acids, vitamin E, and selenium to prevent the expected metabolic alterations induced by physical inactivity and sedentary behaviors. Healthy trained men ( n = 20) (averaging â¼14,000 steps/day and engaged in sports) were randomly divided into a control group (no supplementation) and a cocktail group for a 20-day free-living intervention during which they stopped exercise and decreased their daily steps (averaging â¼3,000 steps/day). During the last 10 days, metabolic changes were further triggered by fructose overfeeding. On days 0, 10, and 20, body composition (dual energy X-ray), blood chemistry, glucose tolerance [oral glucose tolerance test (OGTT)], and substrate oxidation (indirect calorimetry) were measured. OGTT included 1% fructose labeled with (U-13C) fructose to assess liver de novo lipogenesis. Histological changes and related cellular markers were assessed from muscle biopsies collected on days 0 and 20. While the cocktail did not prevent the decrease in insulin sensitivity and its muscular correlates induced by the intervention, it fully prevented the hypertriglyceridemia, the drop in fasting HDL and total fat oxidation, and the increase in de novo lipogenesis. The cocktail further prevented the decrease in the type-IIa muscle fiber cross-sectional area and was associated with lower protein ubiquitination content. The circulating antioxidant capacity was improved by the cocktail following the OGTT. In conclusion, a cocktail of nutrient compounds from dietary origin protects against the alterations in lipid metabolism induced by physical inactivity and fructose overfeeding. NEW & NOTEWORTHY This is the first study to test the efficacy of a novel dietary nutrient cocktail on the metabolic and physiological changes occurring during 20 days of physical inactivity along with fructose overfeeding. The main findings of this study are that 1) reduction in daily steps leads to decreased insulin sensitivity and total fat oxidation, resulting in hyperlipemia and increased de novo lipogenesis and 2) a cocktail supplement prevents the alterations on lipid metabolism.
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Suplementos Dietéticos , Resistencia a la Insulina , Metabolismo de los Lípidos , Atrofia Muscular/prevención & control , Conducta Sedentaria , Antioxidantes/metabolismo , Fructosa , Voluntarios Sanos , Humanos , Masculino , Adulto JovenRESUMEN
Animals that spend more energy than they obtain risk entering allostatic overload, reducing survival and fitness. They are predicted to adjust their daily energy expenditure (DEE) during periods of food scarcity. Adjustments of DEE to changes in food availability have been well-studied in species in temperate zones during winter, but less so in species enduring seasonal droughts. Likely mechanisms regulating DEE involve adjustments of activity and maintenance metabolism. Species that experience seasonal droughts and changes in food availability, like the African striped mouse (Rhabdomys pumilio), are appropriate model organisms to study the regulation of seasonal changes of DEE. We quantified DEE using the 'doubly labelled water' method, measured resting metabolic rate (RMR), and concomitantly determined activity levels using all-day focal observations of 69 free-living striped mice in the cold moist season with high food availability and the hot dry season with low food availability. Striped mice decreased their DEE in the food scarce dry season using multiple mechanisms, especially reductions in RMR, and reduced overall physical activity. This was further facilitated passively by reduced thermoregulatory costs. Our study demonstrates that animals reduce DEE via active and passive mechanisms in food-restricted environments, and highlights that several environmental factors should be considered simultaneously when aiming to understand how animals cope with harsh environments.
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Metabolismo Energético , Estaciones del Año , Animales , Sequías , Femenino , Alimentos , Locomoción , Masculino , Ratones , Lluvia , TemperaturaRESUMEN
For hibernators, being born late in the active season may have important effects on growth and fattening, hence on winter survival and reproduction. This study investigated differences in growth, fattening, energetic responses, winter survival and fecundity between early-born ('EB') and late-born ('LB') juvenile garden dormice (Eliomys quercinus). LB juveniles grew and gained mass twice as fast as EB individuals. Torpor use was low during intensive growth, that are, first weeks of body mass gain, but increased during pre-hibernation fattening. LB juveniles showed higher torpor use, reached similar body sizes but lower fat content than EB individuals before hibernation. Finally, LB individuals showed similar patterns of hibernation, but higher proportion of breeders during the following year than EB dormice. These results suggest that torpor is incompatible with growth but promotes fattening and consolidates pre-hibernation fat depots. In garden dormice, being born late in the reproductive season is associated with a fast life history.
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Fertilidad , Hibernación , Myoxidae/fisiología , Sobrevida , Letargo , Aumento de Peso , Animales , Myoxidae/crecimiento & desarrollo , Estaciones del Año , Factores de TiempoRESUMEN
Context: The effects of energy-balanced bed rest on metabolic flexibility have not been thoroughly examined. Objective: We investigated the effects of 21 days of bed rest, with and without whey protein supplementation, on metabolic flexibility while maintaining energy balance. We hypothesized that protein supplementation mitigates metabolic inflexibility by preventing muscle atrophy. Design and Setting: Randomized crossover longitudinal study conducted at the German Aerospace Center, Cologne, Germany. Participants and Interventions: Ten healthy men were randomly assigned to dietary countermeasure or isocaloric control diet during a 21-day bed rest. Outcome Measures: Before and at the end of the bed rest, metabolic flexibility was assessed during a meal test. Secondary outcomes were glucose tolerance by oral glucose tolerance test, body composition by dual energy X-ray absorptiometry, ectopic fat storage by magnetic resonance imaging, and inflammation and oxidative stress markers. Results: Bed rest decreased the ability to switch from fat to carbohydrate oxidation when transitioning from fasted to fed states (i.e., metabolic inflexibility), antioxidant capacity, fat-free mass (FFM), and muscle insulin sensitivity along with greater fat deposition in muscle (P < 0.05 for all). Changes in fasting insulin and inflammation were not observed. However, glucose tolerance was reduced during acute overfeeding. Protein supplementation did not prevent FFM loss and metabolic alterations. Conclusions: Physical inactivity triggers metabolic inflexibility, even when energy balance is maintained. Although reduced insulin sensitivity and increased fat deposition were observed at the muscle level, systemic glucose intolerance was detected only in response to a moderately high-fat meal. This finding supports the role of physical inactivity in metabolic inflexibility and suggests that metabolic inflexibility precedes systemic glucose intolerance.
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Tejido Adiposo/metabolismo , Reposo en Cama/efectos adversos , Biomarcadores/metabolismo , Metabolismo Energético/fisiología , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/etiología , Resistencia a la Insulina/fisiología , Adiposidad/fisiología , Adulto , Biomarcadores/sangre , Composición Corporal/fisiología , Estudios Cruzados , Dieta , Diagnóstico Precoz , Intolerancia a la Glucosa/metabolismo , Humanos , Estudios Longitudinales , Masculino , Factores de TiempoRESUMEN
The health benefits of chronic caloric restriction resulting in lifespan extension are well established in many short-lived species, but the effects in humans and other primates remain controversial. Here we report the most advanced survival data and the associated follow-up to our knowledge of age-related alterations in a cohort of grey mouse lemurs (Microcebus murinus, lemurid primate) exposed to a chronic moderate (30%) caloric restriction. Compared to control animals, caloric restriction extended lifespan by 50% (from 6.4 to 9.6 years, median survival), reduced aging-associated diseases and preserved loss of brain white matter in several brain regions. However, caloric restriction accelerated loss of grey matter throughout much of the cerebrum. Cognitive and behavioural performances were, however, not modulated by caloric restriction. Thus chronic moderate caloric restriction can extend lifespan and enhance health of a primate, but it affects brain grey matter integrity without affecting cognitive performances.
RESUMEN
BACKGROUND: Previous studies suggested that physical activity energy expenditure (AEE) is a major determinant of dietary fat oxidation, which is a central component of fat metabolism and body weight regulation. OBJECTIVE: We tested this hypothesis by investigating the effect of contrasted physical activity levels on dietary saturated and monounsaturated fatty acid oxidation in relation to insulin sensitivity while controlling energy balance. DESIGN: Sedentary lean men (n = 10) trained for 2 mo according to the current guidelines on physical activity, and active lean men (n = 9) detrained for 1 mo by reducing structured and spontaneous activity. Dietary [d31]palmitate and [1-¹³C]oleate oxidation and incorporation into triglyceride-rich lipoproteins and nonesterified fatty acid, AEE, and muscle markers were studied before and after interventions. RESULTS: Training increased palmitate and oleate oxidation by 27% and 20%, respectively, whereas detraining reduced them by 31% and 13%, respectively (P < 0.05 for all). Changes in AEE were positively correlated with changes in oleate (R² = 0.62, P < 0.001) and palmitate (R² = 0.66, P < 0.0001) oxidation. The d31-palmitate appearance in nonesterified fatty acid and very-low-density lipoprotein pools was negatively associated with changes in fatty acid translocase CD36 (R² = 0.30), fatty acid transport protein 1 (R² = 0.24), and AcylCoA synthetase long chain family member 1 (ACSL1) (R² = 0.25) expressions and with changes in fatty acid binding protein expression (R² = 0.33). The d31-palmitate oxidation correlated with changes in ACSL1 (R² = 0.39) and carnitine palmitoyltransferase 1 (R² = 0.30) expressions (P < 0.05 for all). Similar relations were observed with oleate. Insulin response was associated with AEE (R² = 0.34, P = 0.02) and oleate (R² = 0.52, P < 0.01) and palmitate (R² = 0.62, P < 001) oxidation. CONCLUSION: Training and detraining modified the oxidation of the 2 most common dietary fats, likely through a better trafficking and uptake by the muscle, which was negatively associated with whole-body insulin sensitivity.
Asunto(s)
Grasas de la Dieta/metabolismo , Metabolismo Energético , Ejercicio Físico/fisiología , Peroxidación de Lípido , Ácido Oléico/metabolismo , Palmitatos/metabolismo , Conducta Sedentaria , Acetato CoA Ligasa/metabolismo , Adulto , Carnitina O-Palmitoiltransferasa/metabolismo , Proteínas de Transporte de Ácidos Grasos/metabolismo , Proteínas de Unión a Ácidos Grasos/metabolismo , Ácidos Grasos no Esterificados/metabolismo , Humanos , Insulina/metabolismo , Secreción de Insulina , Lipoproteínas VLDL/metabolismo , Masculino , Oxidación-Reducción , Adulto JovenRESUMEN
A life-long follow-up of physiological and behavioural functions was initiated in 38-month-old mouse lemurs (Microcebus murinus) to test whether caloric restriction (CR) or a potential mimetic compound, resveratrol (RSV), can delay the ageing process and the onset of age-related diseases. Based on their potential survival of 12 years, mouse lemurs were assigned to three different groups: a control (CTL) group fed ad libitum, a CR group fed 70% of the CTL caloric intake and a RSV group (200 mg/kg.day(-1)) fed ad libitum. Since this prosimian primate exhibits a marked annual rhythm in body mass gain during winter, animals were tested throughout the year to assess body composition, daily energy expenditure (DEE), resting metabolic rate (RMR), physical activity and hormonal levels. After 1 year, all mouse lemurs seemed in good health. CR animals showed a significantly decreased body mass compared with the other groups during long day period only. CR or RSV treatments did not affect body composition. CR induced a decrease in DEE without changes in RMR, whereas RSV induced a concomitant increase in DEE and RMR without any obvious modification of locomotor activity in both groups. Hormonal levels remained similar in each group. In summary, after 1 year of treatment CR and RSV induced differential metabolic responses but animals successfully acclimated to their imposed diets. The RESTRIKAL study can now be safely undertaken on a long-term basis to determine whether age-associated alterations in mouse lemurs are delayed with CR and if RSV can mimic these effects.