Molecular and physiologic changes in the SpaceX Inspiration4 civilian crew.

Human spaceflight has historically been managed by government agencies, such as the NASA Twins Study1, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first-ever all civilian crew to low Earth orbit, which included the youngest American astronaut (age 29), novel in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables, and immune profiling), ocular alignment measurements, and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match long-term spaceflight2, but almost all of which did not differ from baseline (pre-flight) after return to Earth. Overall, these preliminary civilian spaceflight data suggest that short-duration missions do not pose a significant health risk, and moreover present a rich opportunity to measure the earliest phases of adaptation to spaceflight in the human body at anatomical, cellular, physiologic, and cognitive levels. Finally, these methods and results lay the foundation for an open, rapidly expanding biomedical database for astronauts3, which can inform countermeasure development for both private and government-sponsored space missions.

Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies.

Decreased skeletal muscle contractile activity (disuse) or unloading leads to muscle mass loss, also known as muscle atrophy. The balance between muscle protein synthesis (MPS) and muscle protein breakdown (MPB) is the primary determinant of skeletal muscle mass. A reduced mechanical load on skeletal muscle is one of the main external factors leading to muscle atrophy. However, endocrine and inflammatory factors can act synergistically in catabolic states, amplifying the atrophy process and accelerating its progression. In addition, older individuals display aging-induced anabolic resistance, which can predispose this population to more pronounced effects when exposed to periods of reduced physical activity or mechanical unloading. Different cellular mechanisms contribute to the regulation of muscle protein balance during skeletal muscle atrophy. This review summarizes the effects of muscle disuse on muscle protein balance and the molecular mechanisms involved in muscle atrophy in the absence or presence of disease. Finally, a discussion of the current literature describing efficient strategies to prevent or improve the recovery from muscle atrophy is also presented.

Insulin rapidly increases skeletal muscle mitochondrial ADP sensitivity in the absence of a high lipid environment.

Reductions in mitochondrial function have been proposed to cause insulin resistance, however the possibility that impairments in insulin signaling negatively affects mitochondrial bioenergetics has received little attention. Therefore, we tested the hypothesis that insulin could rapidly improve mitochondrial ADP sensitivity, a key process linked to oxidative phosphorylation and redox balance, and if this phenomenon would be lost following high-fat diet (HFD)-induced insulin resistance. Insulin acutely (60 min post I.P.) increased submaximal (100-1000 µM ADP) mitochondrial respiration ∼2-fold without altering maximal (>1000 µM ADP) respiration, suggesting insulin rapidly improves mitochondrial bioenergetics. The consumption of HFD impaired submaximal ADP-supported respiration ∼50%, however, despite the induction of insulin resistance, the ability of acute insulin to stimulate ADP sensitivity and increase submaximal respiration persisted. While these data suggest that insulin mitigates HFD-induced impairments in mitochondrial bioenergetics, the presence of a high intracellular lipid environment reflective of an HFD (i.e. presence of palmitoyl-CoA) completely prevented the beneficial effects of insulin. Altogether, these data show that while insulin rapidly stimulates mitochondrial bioenergetics through an improvement in ADP sensitivity, this phenomenon is possibly lost following HFD due to the presence of intracellular lipids.

A higher energy-adjusted Dietary Inflammatory Index is positively associated with total and visceral body fat in young male adults.

BACKGROUND: The energy-adjusted Dietary Inflammatory Index (E-DII™) has been associated with a high body mass index and markers of chronic diseases. Also, pro-inflammatory diets with a high E-DII have been positively associated with metabolic disturbances such as glucose intolerance and type II diabetes mellitus. However, it is unclear whether E-DII scores are positively associated with body fat percentage and visceral fat per se. This cross-sectional study aimed to evaluate whether the E-DII is associated with body fat content and metabolic health indicators in lean and obese young men. METHODS: The present study was conducted on 59 participants, without comorbidities, not using tobacco, medication and nutritional supplements. Dietary data were obtained by 3-day food records to calculate E-DII scores based on 28 food parameters. Body composition was assessed by dual X-ray absorptiometry (DXA). Blood samples were taken to measure fasting glucose, insulin, triacylglycerols, total cholesterol, and low- and high-density lipoprotein cholesterol. An oral glucose tolerance test also was performed. Associations were determined by mixed-effects linear regression. RESULTS: E-DII scores ranged from -3.48 to +3.10. Energy intake was similar across E-DII tertiles. After adjusting for covariates, the highest E-DII tertile was associated with increased body fat, visceral adipose tissue and waist circumference. There was no association between E-DII scores and glycaemic parameters. CONCLUSIONS: In young participants, a dietary pattern with a higher E-DII (i.e., pro-inflammatory) score was associated with high body fat and markers of central adiposity assessed by DXA, regardless of body mass.

In vitro ketone-supported mitochondrial respiration is minimal when other substrates are readily available in cardiac and skeletal muscle.

KEY POINTS: Ketone bodies are proposed to represent an alternative fuel source driving energy production, particularly during exercise. Biologically, the extent to which mitochondria utilize ketone bodies compared to other substrates remains unknown. We demonstrate in vitro that maximal mitochondrial respiration supported by ketone bodies is low when compared to carbohydrate-derived substrates in the left ventricle and red gastrocnemius muscle from rodents, and in human skeletal muscle. When considering intramuscular concentrations of ketone bodies and the presence of other carbohydrate and lipid substrates, biological rates of mitochondrial respiration supported by ketone bodies are predicted to be minimal. At the mitochondrial level, it is therefore unlikely that ketone bodies are an important source for energy production in cardiac and skeletal muscle, particularly when other substrates are readily available. ABSTRACT: Ketone bodies (KB) have recently gained popularity as an alternative fuel source to support mitochondrial oxidative phosphorylation and enhance exercise performance. However, given the low activity of ketolytic enzymes and potential inhibition from carbohydrate oxidation, it remains unknown if KBs can contribute to energy production. We therefore determined the ability of KBs (sodium dl-ß-hydroxybutyrate, ß-HB; lithium acetoacetate, AcAc) to stimulate in vitro mitochondrial respiration in the left ventricle (LV) and red gastrocnemius (RG) of rats, and in human vastus lateralis. Compared to pyruvate, the ability of KBs to maximally drive respiration was low in isolated mitochondria and permeabilized fibres (PmFb) from the LV (∼30-35% of pyruvate), RG (∼10-30%), and human vastus lateralis (∼2-10%). In PmFb, the concentration of KBs required to half-maximally drive respiration (LV: 889 µm ß-HB, 801 µm AcAc; RG: 782 µm ß-HB, 267 µm AcAc) were greater than KB content representative of the muscle microenvironment (∼100 µm). This would predict low rates (∼1-4% of pyruvate) of biological KB-supported respiration in the LV (8-14 pmol s-1 mg-1 ) and RG (3-6 pmol s-1 mg-1 ) at rest and following exercise. Moreover, KBs did not increase respiration in the presence of saturating pyruvate, submaximal pyruvate (100 µm) reduced the ability of physiological ß-HB to drive respiration, and addition of other intracellular substrates (succinate + palmitoylcarnitine) decreased maximal KB-supported respiration. As a result, product inhibition is likely to limit KB oxidation. Altogether, the ability of KBs to drive mitochondrial respiration is minimal and they are likely to be outcompeted by other substrates, compromising their use as an important energy source.

Nitrate attenuates high fat diet-induced glucose intolerance in association with reduced epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission.

KEY POINTS: Dietary nitrate is a prominent therapeutic strategy to mitigate some metabolic deleterious effects related to obesity. Mitochondrial dysfunction is causally linked to adipose tissue inflammation and insulin resistance. Whole-body glucose tolerance is prevented by nitrate independent of body weight and energy expenditure. Dietary nitrate reduces epididymal adipose tissue inflammation and mitochondrial reactive oxygen species emission while preserving insulin signalling. Metabolic beneficial effects of nitrate consumption are associated with improvements in mitochondrial redox balance in hypertrophic adipose tissue. ABSTRACT: Evidence has accumulated to indicate that dietary nitrate alters energy expenditure and the metabolic derangements associated with a high fat diet (HFD), but the mechanism(s) of action remain incompletely elucidated. Therefore, we aimed to determine if dietary nitrate (4 mm sodium nitrate via drinking water) could prevent HFD-mediated glucose intolerance in association with improved mitochondrial bioenergetics within both white (WAT) and brown (BAT) adipose tissue in mice. HFD feeding caused glucose intolerance (P < 0.05) and increased body weight. As a result of higher body weight, energy expenditure increased proportionally. HFD-fed mice displayed greater mitochondrial uncoupling and a twofold increase in uncoupling protein 1 content within BAT. Within epididymal white adipose tissue (eWAT), HFD increased cell size (i.e. hypertrophy), mitochondrial H2 O2 emission, oxidative stress, c-Jun N-terminal kinase phosphorylation and leucocyte infiltration, and induced insulin resistance. Remarkably, dietary nitrate consumption attenuated and/or mitigated all these responses, including rendering mitochondria more coupled within BAT, and normalizing mitochondrial H2 O2 emission and insulin-mediated Akt-Thr308 phosphorylation within eWAT. Intriguingly, the positive effects of dietary nitrate appear to be independent of eWAT mitochondrial respiratory capacity and content. Altogether, these data suggest that dietary nitrate attenuates the development of HFD-induced insulin resistance in association with attenuating WAT inflammation and redox balance, independent of changes in either WAT or BAT mitochondrial respiratory capacity/content.

Cardiovascular and metabolic consequences of the association between chronic stress and high-fat diet in rats.

Obesity and chronic stress are considered independent risk factors for the development of cardiovascular diseases and changes in autonomic system activity. However, the cardiovascular consequences induced by the association between high-fat diet (HFD) and chronic stress are not fully understood. We hypothesized that the association between HFD and exposure to a chronic variable stress (CVS) protocol for four weeks might exacerbate the cardiovascular and metabolic disturbances in rats when compared to these factors singly. To test this hypothesis, male Wistar rats were divided into four groups: control-standard chow diet (SD; n = 8); control-HFD (n = 8); CVS-SD (n = 8); and CVS-HFD (n = 8). The CVS consisted of repeated exposure of the rats to different inescapable and unpredictable stressors (restraint tress; damp sawdust, cold, swim stress and light cycle inversion). We evaluated cardiovascular function, autonomic activity, dietary intake, adiposity and metabolism. The HFD increased body weight, adiposity and blood glucose concentration (∼15%) in both control and CVS rats. The CVS-HFD rats showed decreased insulin sensitivity (25%) compared to CVS-SD rats. The control-HFD and CVS-HFD rats presented increased intrinsic heart rate (HR) values (∼8%). CVS increased cardiac sympathetic activity (∼65%) in both SD- and HFD-fed rats. The HFD increased basal HR (∼10%). Blood pressure and baroreflex analyzes showed no differences among the experimental groups. In conclusion, the present data indicate absence of interaction on autonomic imbalance evoked by either CVS or HFD. Additionally, HFD increased HR and evoked metabolic disruptions which are independent of stress exposure.

Does L-leucine supplementation cause any effect on glucose homeostasis in rodent models of glucose intolerance? A systematic review.

L-Leucine has been used to improve metabolic outcomes in glucose-intolerant rodent models. However, because studies have used different experimental models and conditions it is difficult to establish the best approach for new clinical trials evaluating the potential effects of L-leucine on glucose homeostasis. We performed a systematic review to report the effect of L-leucine supplementation on glucose homeostasis in rodents with glucose intolerance. The search engines MEDLINE and ScienceDirect were applied using MeSH terms. Thirty-four studies were included in this systematic review. Based on the current data, ingestion of 90-140 mg day-1 of isolated L-leucine in diet-induced obesity (DIO) models shows improvement in metabolic markers if offered during the development of the metabolic disorder in almost all the studies, but not after. Branched-chain amino acid supplementation was effective in streptozotocin-induced ß-cells death but not in DIO models. L-Leucine supplementation seems to have an optimal dose and timing for supplementation to improve glucose homeostasis in DIO.

Interference of in vitro hemolysis complete blood count.

BACKGROUND: Hemolysis may occur in vivo, under pathological conditions, or in vitro, related to pre-analytical errors. Hemolyzed samples may produce unreliable results, leading to errors in diagnostic and monitoring evaluations. This study aims to evaluate the interference of in vitro hemolysis on the interpretation of the parameters of the blood cell-counting performed by the impedance method. METHODS: Peripheral blood samples were collected in anticoagulant K2-EDTA and subsequently divided into three 1.0 mL aliquots. The first aliquot was not subjected to any intervention, and the second and third aliquots were passed 5 and 10 times through a small-gauge needle to produce scalar amounts of hemolysis. Hematological tests were performed by Hemacounter 60-RT 7600® . RESULTS: Comparison of the samples with different degrees of hemolysis showed a decrease in red blood cells count and hematocrit counts and increase in mean corpuscular hemoglobin concentration and platelet count in samples with a high degree of hemolysis. According to the accepted clinical point of view, the samples with a high degree of hemolysis exceeded the desirable bias, presenting decrease in red blood cells count, hematocrit and mean corpuscular volume, and increase in red cell distribution width, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet counts. However, samples with a mild degree of hemolysis showed only a slight increase in mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and platelet count. CONCLUSION: This study demonstrated that in vitro hemolysis can decrease the clinical and analytical reliability of the assessment of the blood count.

Glucose homeostasis in two degrees of sepsis lethality induced by caecum ligation and puncture in mice.

Sepsis is associated with high mortality. Both critically ill humans and animal models of sepsis exhibit changes in their glucose homeostasis, that is, hypoglycaemia, with the progression of infection. However, the relationship between basal glycaemia, glucose tolerance and insulin sensitivity is not well understood. Thus, we aimed to evaluate this glucose homeostasis triad at the late stage of sepsis (24 h after surgery) in male Swiss mice subjected to lethal and sublethal sepsis by the caecal ligation and puncture (CLP) model. The percentage of survival 24 h after CLP procedure in the Lethal and Sublethal groups was around 66% and 100% respectively. Both Lethal and Sublethal groups became hypoglycaemic in fasting and fed states 24 h after surgery. The pronounced fed hypoglycaemia in the Lethal group was not due to worsening anorexic behaviour or hepatic inability to deliver glucose in relation to the Sublethal group. Reduction in insulin sensitivity in CLP mice occurred in a lethality-dependent manner and was not associated with glucose intolerance. Analysis of oral and intraperitoneal glucose tolerance tests, as well as the gastrointestinal motility data, indicated that CLP mice had reduced intestinal glucose absorption. Altogether, we suggest cessation of appetite and intestinal glucose malabsorption are key contributors to the hypoglycaemic state observed during experimental severe sepsis.

Does Oil Rich in Alpha-Linolenic Fatty Acid Cause the Same Immune Modulation as Fish Oil in Walker 256 Tumor-Bearing Rats?

OBJECTIVE: Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid. METHODS: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated. RESULTS: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8+) subpopulation, and increased TNF-α production. CONCLUSIONS: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.

Effects of Prebiotic and Synbiotic Supplementation on Inflammatory Markers and Anthropometric Indices After Roux-en-Y Gastric Bypass: A Randomized, Triple-blind, Placebo-controlled Pilot Study.

BACKGROUND: Studies have shown that prebiotics and synbiotics modulate the intestinal microbiota and may have beneficial effects on the immune response and anthropometric indices; however, the impact of the use of these supplements after bariatric surgery is not yet known. GOALS: This study investigated the effects of prebiotic and synbiotic supplementation on inflammatory markers and anthropometric indices in individuals undergoing open Roux-en-Y gastric bypass (RYGB). STUDY: In this randomized, controlled, and triple-blind trial conducted as a pilot study, individuals undergoing RYGB (n=9) and healthy individuals (n=9) were supplemented with 6 g/d of placebo (maltodextrin), prebiotic (fructo-oligosaccharide, FOS), or synbiotic (FOS+Lactobacillus and Bifidobacteria strains) for 15 days. RESULTS: Interleukin-1ß, interleukin-6, tumor necrosis factor-α, C-reactive protein, albumin, and the C-reactive protein/albumin ratio showed no significant changes on comparison between groups after supplementation. The reduction in the body weight of patients undergoing RYGB was 53.8% higher in the prebiotic group compared with the placebo group (-0.7 kg, P=0.001), whereas the reduction in the BMI and the increase in the percentage of excess weight loss were higher in the placebo and the prebiotic groups compared with the synbiotic group (P<0.05). CONCLUSIONS: Supplementation of FOS increased weight loss, whereas both prebiotics and synbiotics were not able to promote significant changes in inflammatory markers, although in most analyses, there was a reduction in their absolute values. The use of FOS may represent a potential adjunct in the treatment of obesity.

Disruption of glucose tolerance caused by glucocorticoid excess in rats is partially prevented, but not attenuated, by arjunolic acid.

Arjunolic acid (AA) obtained from plants of the Combretaceae family has shown anti-diabetic effects. Here, we analyzed whether the diabetogenic effects of dexamethasone (DEX) treatment on glucose homeostasis may be prevented or attenuated by the concomitant administration of AA. Adult Wistar rats were assigned to the following groups: vehicle-treated (Ctl), DEX-treated (1 mg/kg body weight intraperitoneally for 5 days) (Dex), AA-treated (30 mg/kg body weight by oral gavage twice per day) (Aa), AA treatment previous to and concomitant to DEX treatment (AaDex), and AA treatment after initiation of DEX treatment (DexAa). AA administration significantly ameliorated (AaDex) (P > 0.05), but did not attenuate (DexAa), the glucose intolerance induced by DEX treatment. AA did not prevent or attenuate the elevation in hepatic glycogen and triacylglycerol content caused by DEX treatment. All DEX-treated rats exhibited hepatic steatosis that seemed to be more pronounced when associated with AA treatment given for a prolonged period (AaDex). Markers of liver function and oxidative stress were not significantly altered among the groups. Therefore, AA administered for a prolonged period partially prevents the glucose intolerance induced by DEX treatment, but it fails to produce this beneficial effect when given after initiation of GC treatment. Since AA may promote further hepatic steatosis when co-administered with GCs, care is required when considering this phytochemical as a hypoglycemiant and/or insulin-sensitizing agent.

Solubilization of sugarcane bagasse by mono and cocultures of thermophilic anaerobes with and without cotreatment.

Cotreatment, mechanical disruption of lignocellulosic biomass during microbial fermentation, is a potential alternative to thermochemical pretreatment as a means of increasing the accessibility of lignocellulose to biological attack. Successful implementation of cotreatment requires microbes that can withstand milling, while solubilizing and utilizing carbohydrates from lignocellulose. In this context, cotreatment with thermophilic, lignocellulose-fermenting bacteria has been successfully evaluated for a number of lignocellulosic feedstocks. Here, cotreatment was applied to sugarcane bagasse using monocultures of the cellulose-fermenting Clostridium thermocellum and cocultures with the hemicellulose-fermenting Thermoanaerobacterium thermosaccharolyticum. This resulted in 76 % carbohydrate solubilization (a 1.8-fold increase over non-cotreated controls) on 10 g/L solids loading, having greater effect on the hemicellulose fraction. With cotreatment, fermentation by wild-type cultures at low substrate concentrations increased cumulative product formation by 45 % for the monoculture and 32 % for the coculture. These findings highlight the potential of cotreatment for enhancing deconstruction of sugarcane bagasse using thermophilic bacteria.

Whey Protein Supplementation with or without Vitamin D on Sarcopenia-Related Measures: A Systematic Review and Meta-Analysis.

The effects of supplementation with whey protein alone or with vitamin D on sarcopenia-related outcomes in older adults are unclear. We aimed to assess the effect of whey protein supplementation alone or with vitamin D on lean mass (LM), strength, and function in older adults with or without sarcopenia or frailty. We searched PubMed, Web of Science, and SCOPUS databases. Randomized controlled trials (RCT) that investigated the effect of whey protein supplementation with or without vitamin D on sarcopenia outcomes in healthy and sarcopenic or frail older adults were included. Standardized mean differences (SMDs) were calculated for LM, muscle strength, and physical function data. The analysis showed that whey protein supplementation had no effect on LM and muscle strength; nevertheless, a significant improvement was found in physical function (SMD = 0.561; 95% confidence interval [CIs]: 0.256, 0.865, n = 33), particularly gait speed (GS). On the contrary, whey protein supplementation significantly improved LM (SMD = 0.982; 95% CI: 0.228, 1.736; n = 11), appendicular lean mass and physical function (SMD = 1.211; 95% CI: 0.588, 1.834; n = 16), and GS in sarcopenic/frail older adults. By contrast, co-supplementation with vitamin D enhanced LM gains (SMD =0.993; 95% CI: 0.112, 1.874; n = 11), muscle strength (SMD =2.005; 95% CI: 0.975, 3.035; n = 11), and physical function (SMD = 3.038; 95% CI: 2.196, 3.879; n = 18) significantly. Muscle strength and physical function improvements after whey protein supplementation plus vitamin D were observed without resistance exercise (RE) and short study duration subgroups. Moreover, the combination of whey protein and vitamin D with RE did not enhance the effect of RE. Whey protein supplementation improved LM and function in sarcopenic/frail older adults but had no positive effect in healthy older persons. By contrast, our meta-analysis showed that co-supplementation with whey protein and vitamin D is effective, particularly in healthy older adults, which is likely owing, we propose, to the correction of vitamin D insufficiency or deficiency. The trial was registered at https://inplasy.com as INPLASY202240167.

Dietary acid load is positively associated with insulin resistance: a population-based study.

BACKGROUND & AIMS: Diabetes mellitus (DM) and cardiovascular disease (CVD) are among the biggest causes of death and health expenses worldwide. A higher dietary acid load (DAL) is associated with chronic low-grade metabolic acidosis, and may increase the risk of insulin resistance (IR), DM, hypertension, and CVD mortality. However, the association between DAL and IR still lacks population-based studies to confirm laboratory findings. METHODS: This is a population-based observational study including a sample of 545 individuals aged 25-64 years from Florianópolis (Southern Brazil) who participated in the EpiFloripa cohort study. All diet variables were obtained through two 24-h Food Recalls adjusted to obtain an estimate of habitual food consumption. DAL was measured by Potential Renal Acid Load (PRAL) and Net Endogenous Acid production (NEAP). Fasting blood samples were obtained from all participants. The primary outcome was IR, which was estimated by HOMA-IR. Secondary outcomes included HOMA-ß, glycosylated hemoglobin, and fasting blood glucose and insulin. Multiple linear regression models adjusted for sociodemographics, lifestyle, and clinical variables were used for analysis, with exposure and outcome variables standardized as Z-scores to allow comparability of the results. RESULT: The mean PRAL and NEAP in the sample were 16.9 ± 4.8 and 66.1 ± 7.1 mEq/day, respectively. The average HOMA-IR score was 2.4 ± 1.6. In adjusted analyses, PRAL was positively associated with HOMA-IR, fasting insulin, and fasting blood glucose (p-value <0.05 in all cases), but not with HOMA-ß or glycated hemoglobin. NEAP also showed a direct-trend relationship with HOMA-IR and fasting insulin, but not with fasting blood glucose or the other outcomes. The strongest association was between PRAL and HOMA-IR (ß, 0.20; 95% CI, 0.06-0.35). CONCLUSIONS: A higher DAL was consistently associated with higher IR and insulin levels but not with other glycaemic parameters. Apparently, ß-pancreatic cells function is not affected by DAL in this population. This is the first study that describes the DAL in a population-based sample of adults in Latin America and in a middle-income country population. Further longitudinal and interventional studies are required to establish a better causal effect between DAL and IR.

An umbrella review of systematic reviews of ß-hydroxy-ß-methyl butyrate supplementation in ageing and clinical practice.

The compound ß-hydroxy-ß-methyl butyrate (HMB) is proposed to increase or mitigate the loss of skeletal muscle and improve muscle function. We undertook a review of systematic reviews of HMB supplementation to promote gains or mitigate muscle loss in ageing and clinical populations. Following PRISMA guidelines, we searched for systematic reviews reporting the effect of HMB in our target populations. Dual-energy X-ray absorptiometry (DXA) measured lean soft-tissue mass (LSTM) was accepted as a proxy for muscle. We identified 15 systematic reviews that met our inclusion criteria, which were independently evaluated. The methodological quality of the reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and standardized effectiveness statements were generated. Five of 15 studies found some evidence that HMB augmented LSTM; the remaining 10 studies reported some evidence favouring no difference (6/10 studies) or insufficient evidence to determine an effect (4/10 studies). Of the 12 studies that evaluated strength, 4/12 found some evidence, 5/12 found some evidence of no effect with one article finding some evidence in favour of patients in peri-hospitalized and no evidence for those that are community-dwelling, 4/12 had insufficient evidence to determine an effect, and 1/12 had insufficient evidence. No]study reported a positive effect of HMB on physical function; however, 2/10 studies found some evidence favouring no effect, and 7/10 studies reported insufficient evidence to determine an effect. The effectiveness of HMB supplementation in augmenting LSTM was heterogeneous, with most reviews finding no effect or inconclusive evidence to determine an effect. Most reviews concluded that HMB supplementation did not affect strength outcome measures or studies were inconclusive. The current evidence is insufficient to assess the impact of HMB supplementation on functional outcome measures. Our analysis shows minor, inconsistent support for HMB as part of an oral nutritional supplement or as a stand-alone supplement (or combined with other amino acids) to increase or promote retention of LSTM, improve strength, and no evidence that it improves physical function in older persons or clinical populations.

Nitrate consumption preserves HFD-induced skeletal muscle mitochondrial ADP sensitivity and lysine acetylation: A potential role for SIRT1.

Dietary nitrate supplementation, and the subsequent serial reduction to nitric oxide, has been shown to improve glucose homeostasis in several pre-clinical models of obesity and insulin resistance. While the mechanisms remain poorly defined, the beneficial effects of nitrate appear to be partially dependent on AMPK-mediated signaling events, a central regulator of metabolism and mitochondrial bioenergetics. Since AMPK can activate SIRT1, we aimed to determine if nitrate supplementation (4 mM sodium nitrate via drinking water) improved skeletal muscle mitochondrial bioenergetics and acetylation status in mice fed a high-fat diet (HFD: 60% fat). Consumption of HFD induced whole-body glucose intolerance, and within muscle attenuated insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity (higher apparent Km), submaximal ADP-supported respiration, mitochondrial hydrogen peroxide (mtH2O2) production in the presence of ADP and increased cellular protein carbonylation alongside mitochondrial-specific acetylation. Consumption of nitrate partially preserved glucose tolerance and, within skeletal muscle, normalized insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity, mtH2O2, protein carbonylation and global mitochondrial acetylation status. Nitrate also prevented the HFD-mediated reduction in SIRT1 protein, and interestingly, the positive effects of nitrate ingestion on glucose homeostasis and mitochondrial acetylation levels were abolished in SIRT1 inducible knock-out mice, suggesting SIRT1 is required for the beneficial effects of dietary nitrate. Altogether, dietary nitrate preserves mitochondrial ADP sensitivity and global lysine acetylation in HFD-fed mice, while in the absence of SIRT1, the effects of nitrate on glucose tolerance and mitochondrial acetylation were abrogated.

An Evidence-Based Narrative Review of Mechanisms of Resistance Exercise-Induced Human Skeletal Muscle Hypertrophy.

Skeletal muscle plays a critical role in physical function and metabolic health. Muscle is a highly adaptable tissue that responds to resistance exercise (RE; loading) by hypertrophying, or during muscle disuse, RE mitigates muscle loss. Resistance exercise training (RET)-induced skeletal muscle hypertrophy is a product of external (e.g., RE programming, diet, some supplements) and internal variables (e.g., mechanotransduction, ribosomes, gene expression, satellite cells activity). RE is undeniably the most potent nonpharmacological external variable to stimulate the activation/suppression of internal variables linked to muscular hypertrophy or countering disuse-induced muscle loss. Here, we posit that despite considerable research on the impact of external variables on RET and hypertrophy, internal variables (i.e., inherent skeletal muscle biology) are dominant in regulating the extent of hypertrophy in response to external stimuli. Thus, identifying the key internal skeletal muscle-derived variables that mediate the translation of external RE variables will be pivotal to determining the most effective strategies for skeletal muscle hypertrophy in healthy persons. Such work will aid in enhancing function in clinical populations, slowing functional decline, and promoting physical mobility. We provide up-to-date, evidence-based perspectives of the mechanisms regulating RET-induced skeletal muscle hypertrophy.

Heart rate reactivity to acute mental stress is associated with adiposity, carotid distensibility, sleep efficiency, and autonomic modulation in young men.

Acute mental stress (AMS) increases heart rate (HR) and blood pressure. Since obesity can impair the cardiovascular reactivity to AMS, a better understanding of the mechanisms involved in this response is needed. We aimed to evaluate the cardiovascular reactivity to AMS in young men with normal or excess body fat. We also assessed the association between cardiovascular reactivity to AMS and cardiovascular risk factors, including autonomic modulation, carotid artery distensibility, physical activity levels, and sleep efficiency. Sixty-six young men (26.1 ± 4.1 years old) underwent anthropometric and body fat assessment (dual-energy X-ray absorptiometry) and had right-carotid artery ultrasonography. Accelerometers assessed physical activity levels and sleep efficiency. AMS was induced through the Stroop color-word test while blood pressure, HR, and cardiac interval were measured. Analyses were performed in Normal and Excess fat groups divided by fat mass index (FMI). Continuous data was used for multiple linear regression analyses. An interaction between FMI and time for HR reactivity was observed. Cardiac interval variability analysis showed that only participants with normal fat displayed parasympathetic withdrawal during AMS (P < 0.05). Multiple linear regression analysis supported the role of adiposity and autonomic modulation in the HR reactivity to AMS and showed involvement of carotid distensibility and sleep efficiency (P < 0.05). Carotid distensibility was the only predictor for blood pressure reactivity (P < 0.05). Physical activity was not associated with AMS's cardiovascular reactivity. We conclude that increased adiposity is associated with reduced HR reactivity to AMS, which is possibly linked to an impaired parasympathetic withdrawal. Carotid distension and sleep efficiency seem to contribute to this response.