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Background:Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined.Materials and Methods:Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, β-oxidation, lipolysis and cysteine oxidation.Results:Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery.Conclusions:These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PurposeTo compare concentric and eccentric cycling performed by older adults for metabolic demand and post-exercise oxidative stress, inflammation and muscle damage.MethodsEight male and two female healthy older adults (60.4 ± 6.8 years) performed 30 min of moderate-intensity concentric (CONC-M: 50% maximum power output; POmax) and eccentric cycling (ECC-M: 50% POmax) and high-intensity eccentric cycling (ECC-H: 100% POmax) in a randomized order. Average power output (PO), oxygen consumption (VO2), heart rate (HR) and rate of perceived exertion were recorded during cycling. Some indirect markers of muscle damage were assessed before, and immediately, 24 and 48 h after cycling. Markers of oxidative stress (malondialdehyde: MDA, protein carbonyl), antioxidant (total antioxidant capacity, glutathione peroxidase activity: GPx) and inflammation (IL-6, TNF-α) were measured before and 5 min after cycling.ResultsPO in ECC-H (202.6 ± 78.5 W) was > 50% greater (P < 0.05) than that of CONC-M (98.6 ± 33.1 W) and ECC-M (112.0 ± 42.1 W). VO2 and HR were also greater (P < 0.05) for ECC-H than CONC-M (50% and 17%, respectively) and ECC-M (40% and 23%, respectively). Muscle strength loss at 1 day post-exercise (8–22%), peak soreness (10–62 mm) and creatine kinase activity (30–250 IU/L) after ECC-H were greater (P < 0.05) than those after ECC-M and CONC-M. MDA decreased (P < 0.05) after CONC-M (− 28%) and ECC-M (− 22%), but not after ECC-H. GPx activity increased after all exercises similarly (20–27%). IL-6 increased (P < 0.05) only after ECC-H (18%).ConclusionOxidative stress was minimal after eccentric cycling, but high-intensity eccentric cycling induced moderate muscle damage and inflammation, which is not desirable for older individuals.

Peripheral insulin resistance is linked to an increase in reactive oxygen species (ROS), leading in part to the production of reactive lipid aldehydes that modify the side chains of protein amino acids in a reaction termed protein carbonylation. The primary enzymatic method for lipid aldehyde detoxification is via glutathione S-transferase A4 (GSTA4) dependent glutathionylation. The objective of this study was to evaluate the expression of GSTA4 and the role(s) of protein carbonylation in adipocyte function. GSTA4-silenced 3T3-L1 adipocytes and GSTA4-null mice were evaluated for metabolic processes, mitochondrial function, and reactive oxygen species production. GSTA4 expression in human obesity was evaluated using microarray analysis. GSTA4 expression is selectively downregulated in adipose tissue of obese insulin-resistant C57BL/6J mice and in human obesity-linked insulin resistance. Tumor necrosis factor-alpha treatment of 3T3-L1 adipocytes decreased GSTA4 expression, and silencing GSTA4 mRNA in cultured adipocytes resulted in increased protein carbonylation, increased mitochondrial ROS, dysfunctional state 3 respiration, and altered glucose transport and lipolysis. Mitochondrial function in adipocytes of lean or obese GSTA4-null mice was significantly compromised compared with wild-type controls and was accompanied by an increase in superoxide anion. These results indicate that downregulation of GSTA4 in adipose tissue leads to increased protein carbonylation, ROS production, and mitochondrial dysfunction and may contribute to the development of insulin resistance and type 2 diabetes.

In potentially severe diseases in general and COVID-19 in particular, it is vital to early identify those patients who are going to progress to severe disease. A recent living systematic review dedicated to predictive models in COVID-19, critically appraises 145 models, 8 of them focused on prediction of severe disease and 23 on mortality. Unfortunately, in all 145 models, they found a risk of bias significant enough to finally \"not recommend any for clinical use\". Authors suggest concentrating on avoiding biases in sampling and prioritising the study of already identified predictive factors, rather than the identification of new ones that are often dependent on the database. Our objective is to develop a model to predict which patients with COVID-19 pneumonia are at high risk of developing severe illness or dying, using basic and validated clinical tools. We studied a prospective cohort of consecutive patients admitted in a teaching hospital during the “first wave” of the COVID-19 pandemic. Follow-up to discharge from hospital. Multiple logistic regression selecting variables according to clinical and statistical criteria. 404 consecutive patients were evaluated, 392 (97%) completed follow-up. Mean age was 61 years; 59% were men. The median burden of comorbidity was 2 points in the Age-adjusted Charlson Comorbidity Index, CRB was abnormal in 18% of patients and basal oxygen saturation on admission lower than 90% in 18%. A model composed of Age-adjusted Charlson Comorbidity Index, CRB score and basal oxygen saturation can predict unfavorable evolution or death with an area under the ROC curve of 0.85 (95% CI 0.80–0.89), and 0.90 (95% CI 0.86 to 0.94), respectively. Prognosis of COVID-19 pneumonia can be predicted without laboratory tests using two classic clinical tools and a pocket pulse oximeter.

Background Hydration status affects endurance performance. Pre-exercise hydration recommendations target the consumption of high carbohydrate and sodium beverages. Milk, due to its carbohydrate and sodium content, may be considered an effective pre-exercise hydration beverage. Purpose In a randomized cross-over trial, we compared the effects of an isotonic sport drink (SPD) with skim milk (SM) consumption before a race, on fluid homeostasis and time-trial performance in road cyclists. Methods Male road cyclists ( n  = 9; age, 26.8 ± 4.78 years) with 10.8 ± 8.56 years of experience in national competitions, consumed either SPD or SM in doses of 350 mL at 3 h and 350 mL at 1.5 h before a 18.6 km time-trial race. Measurements of body mass, urine specific gravity (USG), urine color and time-trial were compared between drinks (group; g) before and after the race (time; t). Results The two-way ANOVA showed no differences between SPD and SM in body mass (t, p  < 0.0001; g, p  = 0.89; t × g, p  = 0.54), USG (t, p  = 0.01; g, p  = 0.63; t × g, p  = 0.29) and urine color (t, p  = 0.01; g, p  = 0.54; t × g, p  = 0.28) before or after race. Furthermore, no differences on water consumption during the race ( p  = 0.55) or time-trial performance ( p  = 0.84) were observed between trials. Conclusion Current results may help athletes with different beverages preferences to increase their options of hydration strategies.

Fluid and electrolyte status have a significant impact on physical performance and health. Pre-exercise recommendations cite the possibility of consuming beverages with high amounts of sodium. In this sense, non-alcoholic beer can be considered an effective pre-exercise hydration beverage. This double-blind, randomized study aimed to compare the effect of beer, non-alcoholic beer and water consumption before exercise on fluid and electrolyte homeostasis. Seven male soccer players performed 45 min of treadmill running at 65% of the maximal heart rate, 45 min after ingesting 0.7 L of water (W), beer (AB) or non-alcoholic beer (NAB). Body mass, plasma Na+ and K+ concentrations and urine specific gravity (USG) were assessed before fluid consumption and after exercise. After exercise, body mass decreased (p < 0.05) in W (−1.1%), AB (−1.0%) and NAB (−1.0%). In the last minutes of exercise, plasma Na+ was reduced (p < 0.05) in W (−3.9%) and AB (−3.7%), plasma K+ was increased (p < 0.05) in AB (8.5%), and USG was reduced in W (−0.9%) and NAB (−1.0%). Collectively, these results suggest that non-alcoholic beer before exercise could help maintain electrolyte homeostasis during exercise. Alcoholic beer intake reduced plasma Na+ and increased plasma K+ during exercise, which may negatively affect health and physical performance, and finally, the consumption of water before exercise could induce decreases of Na+ in plasma during exercise.

Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1-/- donors. PD-L1-deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1-/- donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell-mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD.

The aim of the present study was to test if the consumption of creatine incorporated in food bars modifies creatine plasma kinetics, erythrocyte retention and loss in urine and in feces when compared with its consumption in the form of an aqueous solution (AS). Seventeen healthy young men ingested 2 g creatine either in the form of AS, or incorporated in a protein (PP)- or in a beta-glucan (BG)-rich food bar. Kinetics of plasma creatine was measured for 8-h duration and urinary excretion for 24 h. Then, the subjects received the same treatment thrice a day for 1 week at the end of which creatine contents were determined in erythrocytes and in feces ( n  = 4 for feces). The three crossover treatments were interspaced by a 40 ± 1.2-day wash-out. Absorption of creatine was slowed down by 8-fold in the presence of BG ( P  < 0.001) and by 4-fold with PP ( P  < 0.001) whereas the velocity rate constant of elimination and the area under the curve were not modified. Urinary loss of creatine in the first 24 h following ingestion was 15 ± 1.9% in AS and 14 ± 2.2% in PP conditions (NS), whereas it was only 8 ± 1.2% with BG ( P  = 0.004). Increase in creatine concentration in erythrocyte was similar in whatever form the creatine was ingested. Creatine seems to be totally absorbed since no creatine or creatinine was detectable in feces. No side effects were reported. In conclusion, ingestion of creatine combined with BG facilitates its retention by slowing down its absorption rate and reducing its urinary excretion.

Dehydration in rodents induces anorexia. In humans however, the role of dehydration in energy intake is controversial. This study investigated the effect of extreme fluid restriction on acute energy intake during and after exercise-induced dehydration. Eight physically active participants performed two exercise sessions to induce dehydration. After the exercise, the men were allowed to either rehydrate for 2 h or were maintained in a hypohydrated state, in a randomized manner. After 2 h, they were given cereal bars ad libitum for 1 h. Blood and saliva samples of the participants were collected before the exercise session, after the exercise session, after rehydration, and after the meal. Post-exercise energy intake differed between hypohydrated (1430 ± 210 kcal) and rehydrated (2190 ± 780 kcal) trials (p = 0.01). For the concentrations of ghrelin and leptin, there were no significant effects of time (p = 0.94, p = 0.21), between trials (p = 0.09, p = 0.99), or due to a trial–time interaction (p = 0.64, p = 0.68), respectively. The concentrations of peptide YY (PYY) were not different between trials (p = 0.94) but there was a significant effect of time (p = 0.0001) and a trial–time interaction (p = 0.01), with higher levels in the rehydration trial after eating in response to a higher energy intake. For saliva production, there was a significant effect of time (p = 0.02) and a trial–time interaction (p = 0.04), but no between-trial effect (p = 0.08). In conclusion, extreme fluid restriction decreased acute food intake after exercise, which may be explained by a lower flow of saliva.