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Tyrosinemia type 1 (TT1) is caused by fumarylacetoacetate hydrolase activity deficiency, resulting in tissue accumulation of upstream metabolites, including succinylacetone (SA), the pathognomonic compound of this disease. Since the pathogenesis of liver and kidney damage observed in the TT1-affected patients is practically unknown, this study assessed the effects of SA on important biomarkers of redox homeostasis in the liver and kidney of adolescent rats, as well as in hepatic (HepG2) and renal (HEK-293) cultured cells. SA significantly increased nitrate and nitrite levels and decreased the concentrations of reduced glutathione (GSH) in the liver and kidney, indicating induction of reactive nitrogen species (RNS) generation and disruption of antioxidant defenses. Additionally, SA decreased the GSH levels and the activities of glutathione peroxidase, glutathione S-transferase, glutathione reductase, and superoxide dismutase in hepatic and renal cells. Noteworthy, melatonin prevented the SA-induced increase of nitrate and nitrite levels in the liver. Therefore, SA-induced increase of RNS generation and impairment of enzymatic and nonenzymatic antioxidant defenses may contribute to hepatopathy and renal disease in TT1., (© 2024 John Wiley & Sons Ltd.)

It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls ( n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition ( p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity ( p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities ( p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels ( p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.

Background: Chronic pain (CP) and thyroid hormones' (TH) abnormalities are associated with depression, but the impact of pain and TH fluctuation on the response to depression treatment is uncertain., Methods: Eighty-eight patients with major depression were evaluated before and after 6 months of specific treatment, through scales of symptoms' severity (HAM-D-17), psychomotor disturbance (CORE), and quality of life (WHOQOL-Bref). We reviewed psychiatric medications and measured TSH, T3 and T4. We used Generalized Estimating Equations to assess the interaction effect between CP and treatment time on depression severity and TH levels, and Bonferroni to compare means., Results: 47.7 % of the patients had CP. Patients with and without CP did not differ at baseline. At follow-up, those with CP experienced a more modest decrease in symptoms' severity and no improvement in any domain of psychomotor disturbance, contrasting with a decrease of over 40 % from the baseline values of CORE in patients without CP (non-CP). Initial and final scores were respectively: HAM-D CP 24.06 and 19.3, Δ = -4.75; HAM-D non-CP 22.92 and 14.7, Δ = -8.21; CORE CP 5.36 and 5.24, Δ = -0.12; CORE non-CP 5.8 and 3.22, Δ = -2.57. There was no interaction with TH or life quality. Model adjustments for psychotropic drugs received and sensitivity analysis excluding somatic symptoms from severity scales did not impact the results., Limitations: Findings may not replicate in mildly depressed patients from primary care. Pain scales were not applied., Conclusions: Individuals with chronic pain showed a suboptimal response to depression treatment, regardless of the medications used or TH levels., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Refsum disease is an inherited peroxisomal disorder caused by severe deficiency of phytanoyl-CoA hydroxylase activity. Affected patients develop severe cardiomyopathy of poorly known pathogenesis that may lead to a fatal outcome. Since phytanic acid (Phyt) concentrations are highly increased in tissues of individuals with this disease, it is conceivable that this branched-chain fatty acid is cardiotoxic. The present study investigated whether Phyt (10-30 μM) could disturb important mitochondrial functions in rat heart mitochondria. We also determined the influence of Phyt (50-100 μM) on cell viability (MTT reduction) in cardiac cells (H9C2). Phyt markedly increased mitochondrial state 4 (resting) and decreased state 3 (ADP-stimulated) and uncoupled (CCCP-stimulated) respirations, besides reducing the respiratory control ratio, ATP synthesis and the activities of the respiratory chain complexes I-III, II, and II-III. This fatty acid also reduced mitochondrial membrane potential and induced swelling in mitochondria supplemented by exogenous Ca 2+ , which were prevented by cyclosporin A alone or combined with ADP, suggesting the involvement of the mitochondrial permeability transition (MPT) pore opening. Mitochondrial NAD(P)H content and Ca 2+ retention capacity were also decreased by Phyt in the presence of Ca 2+ . Finally, Phyt significantly reduced cellular viability (MTT reduction) in cultured cardiomyocytes. The present data indicate that Phyt, at concentrations found in the plasma of patients with Refsum disease, disrupts by multiple mechanisms mitochondrial bioenergetics and Ca 2+ homeostasis, which could presumably be involved in the cardiomyopathy of this disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Accumulation of D-2-hydroxyglutaric acid (D-2-HG) is the biochemical hallmark of D-2-hydroxyglutaric aciduria type I and, particularly, of D-2-hydroxyglutaric aciduria type II (D2HGA2). D2HGA2 is a metabolic inherited disease caused by gain-of-function mutations in the gene isocitrate dehydrogenase 2. It is clinically characterized by neurological abnormalities and a severe cardiomyopathy whose pathogenesis is still poorly established. The present work investigated the potential cardiotoxicity D-2-HG, by studying its in vitro effects on a large spectrum of bioenergetics parameters in heart of young rats and in cultivated H9c2 cardiac myoblasts. D-2-HG impaired cellular respiration in purified mitochondrial preparations and crude homogenates from heart of young rats, as well as in digitonin-permeabilized H9c2 cells. ATP production and the activities of cytochrome c oxidase (complex IV), alpha-ketoglutarate dehydrogenase, citrate synthase and creatine kinase were also inhibited by D-2-HG, whereas the activities of complexes I, II and II-III of the respiratory chain, glutamate, succinate and malate dehydrogenases were not altered. We also found that this organic acid compromised mitochondrial Ca 2+ retention capacity in heart mitochondrial preparations and H9c2 myoblasts. Finally, D-2-HG reduced the viability of H9c2 cardiac myoblasts, as determined by the MTT test and by propidium iodide incorporation. Noteworthy, L-2-hydroxyglutaric acid did not change some of these measurements (complex IV and creatine kinase activities) in heart preparations, indicating a selective inhibitory effect of the enantiomer D. In conclusion, it is presumed that D-2-HG-disrupts mitochondrial bioenergetics and Ca 2+ retention capacity, which may be involved in the cardiomyopathy commonly observed in D2HGA2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Metabolic dysfunction-associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that thyroid hormone triiodothyronine (T3) regulates hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of type 3 deiodinase (D3) contributes to MAFLD, but its role is not fully understood., Objective: To evaluate the role of D3 in the progression of MAFLD in an animal model., Methodology: Male/adult Sprague Dawley rats (n = 20) were allocated to a control group (2.93 kcal/g) and high-fat diet group (4.3 kcal/g). Euthanasia took place on the 28th week. D3 activity and expression, Uncoupling Protein 2 (UCP2) and type 1 deiodinase (D1) expression, oxidative stress status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured., Results: We observed an increase in D3 activity/expression ( p < 0.001) related to increased thiobarbituric acid reactive substances (TBARS) and carbonyls and diminished reduced glutathione (GSH) in the MAFLD group ( p < 0.05). There was a D3-dependent decrease in UCP2 expression ( p = 0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group ( p < 0.001). Surprisingly, in an environment with lower T3 levels due to high D3 activity, we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydrogenase (GDH) enzymes activity ( p < 0.05)., Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability and hepatic mitochondrial capacity. The Krebs cycle enzymes were altered as well as endoplasmic reticulum stress. Taken together, these results shed new light on the role of D3 metabolism in MAFLD.

Low T3 syndrome occurs frequently in patients with sepsis. Type 3 deiodinase (DIO3) is present in immune cells, but there is no description of its presence in patients with sepsis. Here, we aimed to determine the prognostic impact of thyroid hormones levels (TH), measured on ICU admission, on mortality and evolution to chronic critical illness (CCI) and the presence of DIO3 in white cells. We used a prospective cohort study with a follow-up for 28 days or deceased. Low T3 levels at admission were present in 86.5% of the patients. DIO3 was induced by 55% of blood immune cells. The cutoff value of 60 pg/mL for T3 displayed a sensitivity of 81% and specificity of 64% for predicting death, with an odds ratio of 4.89. Lower T3 yielded an area under the receiver operating characteristic curve of 0.76 for mortality and 0.75 for evolution to CCI, thus displaying better performance than commonly used prognostic scores. The high expression of DIO3 in white cells provides a novel mechanism to explain the reduction in T3 levels in sepsis patients. Further, low T3 levels independently predict progression to CCI and mortality within 28 days for sepsis and septic shock patients.

Propionic acid (PA) predominantly accumulates in tissues and biological fluids of patients affected by propionic acidemia that may manifest chronic renal failure along development. High urinary excretion of maleic acid (MA) has also been described. Considering that the underlying mechanisms of renal dysfunction in this disorder are poorly known, the present work investigated the effects of PA and MA (1-5 mM) on mitochondrial functions and cellular viability in rat kidney and cultured human embryonic kidney (HEK-293) cells. Mitochondrial membrane potential (∆ψm), NAD(P)H content, swelling and ATP production were measured in rat kidney mitochondrial preparations supported by glutamate or glutamate plus malate, in the presence or absence of Ca 2+ . MTT reduction and propidium iodide (PI) incorporation were also determined in intact renal cells pre-incubated with MA or PA for 24 h. MA decreased Δψm and NAD(P)H content and induced swelling in Ca 2+ -loaded mitochondria either respiring with glutamate or glutamate plus malate. Noteworthy, these alterations were fully prevented by cyclosporin A plus ADP, suggesting the involvement of mitochondrial permeability transition (mPT). MA also markedly inhibited ATP synthesis in kidney mitochondria using the same substrates, implying a strong bioenergetics impairment. In contrast, PA only caused milder changes in these parameters. Finally, MA decreased MTT reduction and increased PI incorporation in intact HEK-293 cells, indicating a possible association between mitochondrial dysfunction and cell death in an intact cell system. It is therefore presumed that the MA-induced disruption of mitochondrial functions involving mPT pore opening may be involved in the chronic renal failure occurring in propionic acidemia., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Cardiac rehabilitation with aerobic exercises is the first strategy for nonpharmacological treatment in the postoperative period of individuals undergoing coronary artery bypass grafting (CABG) to improve functional capacity and vascular health. However, other exercise modalities remain uncertain regarding the same benefits. Objectives: Evaluation of the effect of different modalities of exercise, such as early cardiac rehabilitation on subjects submitted to CABG in the six-minute walk test (6-MWT) and on the percentage of flow-mediated dilatation (FMD) of the brachial artery. Methods: A randomized clinical trial in which 15 patients (62.7 ± 6.7 years) who underwent CABG were randomly assigned to the following groups: isometric (IG, Handgrip Jamar®), ventilatory muscle training (VG, PowerBreathe®) and control (CG, conventional respiratory and motor physiotherapy). All patients were attended to physically twice a day (20 min/session) for a consecutive week after the CABG (hospital admission). Functional capacity was assessed by 6-MWT and endothelial function was assessed through the technique of FMD, before and after (~7 days) admission to CABG. The doppler ultrasound videos were analyzed by Cardiovascular Suite® software (Quipu, Pisa, Italy) to measure %FMD. Statistics: Generalized estimation equation, followed by Bonferroni post hoc (p < 0.05). Results: Systolic, diastolic and mean arterial pressure (SBP/DBP/MAP, respectively) were 133, 76 and 95 mmHg. The groups presented walking meters (m) distance before and after intervention of: IGbasal 357.80 ± 47.15 m vs. IGpost 306.20 ± 61.63 m, p = 0.401 (+51 m); VGbasal 261.50 ± 19.91 m vs. VGpost 300.75 ± 26.29 m, p = 0.052 (+39 m); CG basal 487.83 ± 83.23 m vs. CGpost 318.00 ± 31.08, p = 0.006 (−169 m). %FMD before and after intervention was IGbasal 10.4 ± 4.8% vs. IGpost 2.8 ± 2.5%, p = 0.152; VGbasal 9.8 ± 5.1% vs. VGpost 11.0 ± 6.1%, p = 0.825; CGbasal 9.2 ± 15.8% vs. CGpost 2.7 ± 2.6%, p = 0.710 and resting mean basal blood flow was IGbasal 162.0 ± 55.0 mL/min vs. IGpost 129.9 ± 63.7 mL/min, p = 0.662; VGbasal 83.74 ± 12.4 mL/min vs. VGpost 58.7 ± 17.1 mL/min, p = 0.041; CGbasal 375.6 ± 183.7 mL/min vs. CGpost 192.8 ± 115.0 mL/min, p = 0.459. Conclusions: Ventilatory muscle training for early cardiac rehabilitation improved acute functional capacity and modulated mean flow of individuals undergoing CABG.

We performed a systematic review of the mechanisms of thyroid hormones (THs) associated with metabolic dysfunction associated with fatty liver disease (MAFLD). This systematic review was registered under PROSPERO (CRD42022323766). We searched the MEDLINE (via PubMed) and Embase databases from their inception to March 2022. We included studies that assessed thyroid function by measuring the serum level of THs and those involved in MAFLD. We excluded reviews, case reports, editorials, letters, duplicate studies and designed controls. Forty-three studies included MAFLD, eleven analyzed THs, and thirty-two evaluated the mechanisms of THs in MAFLD. Thyroid hormones are essential for healthy growth, development and tissue maintenance. In the liver, THs directly influence the regulation of lipid and carbohydrate metabolism, restoring the homeostatic state of the body. The selected studies showed an association of reduced levels of THs with the development and progression of MAFLD. In parallel, reduced levels of T3 have a negative impact on the activation of co-regulators in the liver, reducing the transcription of genes important in hepatic metabolism. Overall, this is the first review that systematically synthesizes studies focused on the mechanism of THs in the development and progression of MAFLD. The data generated in this systematic review strengthen knowledge of the impact of TH changes on the liver and direct new studies focusing on therapies that use these mechanisms.

The muscle stem-cell niche comprises numerous cell types, which coordinate the regeneration process after injury. Thyroid hormones are one of the main factors that regulate genes linked to skeletal muscle. In this way, deiodinase types 2 and 3 are responsible for the fine-tuning regulation of the local T3 amount. Although their expression and activity have already been identified during muscle regeneration, it is of utmost importance to identify the cell type and temporal pattern of expression after injury to thoroughly comprehend their therapeutic potential. Here, we confirmed the expression of Dio2 and Dio3 in the whole tibialis anterior muscle. We identified, on a single-cell basis, that Dio2 is present in paired box 7 (PAX7)-positive cells starting from day 5 after injury. Dio2 is present in platelet derived growth factor subunit A (PDGFA)-expressing fibro-adipogenic progenitor cells between days 7 and 14 after injury. Dio3 is detected in myogenic differentiation (MYOD)-positive stem cells and in macrophages immediately post injury and thereafter. Interestingly, Dio2 and Dio3 RNA do not appear to be present in the same type of cell throughout the process. These results provide further insight into previously unseen aspects of the crosstalk and synchronized regulation of T3 in injured muscle mediated by deiodinases. The set of findings described here further define the role of deiodinases in muscle repair, shedding light on potential new forms of treatment for sarcopenia and other muscular diseases.

We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of non-thyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone (TH) level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients from 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% CI, 0.41-1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31-0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in thyrotropin levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (odds ratio (OR) = 2.21, 95% CI, 1.64-2.97, I2 = 65% P < 0.01). The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.

To examine the acute effects of aerobic exercise (AE), resistance exercise (RE) or combined exercise (CE) on flow-mediated dilation (FMD), progenitor cells (PCs), endothelial progenitor cells (EPCs), oxidative stress markers and endothelial-cell derived microvesicles (EMVs) in patients with hypertension. This is a randomized, parallel-group clinical trial involving an intervention of one session of three different modalities of exercise. Thirty-three males (43 ± 2y) were randomly divided into three groups: a session of AE (n = 11, 40 min, cycle ergometer, 60% HRR); a session of RE (n = 11, 40 min, 4 × 12 lower limb repetitions, 60% 1-RM); or a session of CE (n = 11, 20-min RE + 20-min AE). FMD was assessed 10 min before and 10, 40 and 70 min post-intervention. Blood samples were collected at the same time points (except 40 min). FMD were similar in all groups and from baseline (within each group) after a single exercise bout (AE, RE or CE). At 70 min, RE group showed higher levels of PCs compared to the AE (81%) and CE group (60%). PC levels were reduced from baseline in all groups (AE: 32%, p = 0.037; RE: 15%, p = 0.003; CE: 17%, p = 0.048). The levels of EPCs, EMVs and oxidative stress were unchanged. There were no acute effects of moderate-intensity exercise on FMD, EPCs, EMVs and oxidative stress, but PCs decreased regardless of the exercise modality. Individuals with controlled hypertension do not seem to have impaired vascular function in response to a single exercise bout.

Endothelial dysfunction is a characteristic of systemic arterial hypertension (SAH) and an early marker of atherosclerosis. Aerobic exercise training (AT) improves endothelial function. However, the effects of resistance training (RT) and combined training (CT) on endothelial function remain controversial in individuals with SAH. We determined the effects of AT, RT, and CT on endothelial function and systolic (SBP)/diastolic blood pressure (DBP) in individuals with prehypertension or hypertension. Forty-two participants (54 ± 11 y, resting SBP/DBP 137 ± 9/86 ± 6 mmHg) were randomly allocated into AT (n = 14, 40 min of cycling, 50-75% heart rate reserve), RT (n = 14, 6 resistance exercises, 4 × 12 repetitions, 60% maximum strength) and CT (n = 14, 2 × 12 repetitions of RT + 20 min of AT). All participants performed a 40-minute exercise session twice a week for 8 weeks. Endothelial function was evaluated by brachial artery flow-mediated dilation (FMD). Blood pressure was evaluated through ambulatory monitoring for 24 hours. After 8 weeks of exercise training, blood pressure was reduced in all 3 groups: -5.1 mmHg in SBP (95%CI -10.1, 0.0; p = 0.003) in AT; -4.0 mmHg in SBP (95%CI -7.8, -0.5; p = 0.027) in RT; and -3.2 mmHg in DBP (95%CI -7.9, 1.5; p = 0.001) in CT. All 3 exercise training modalities produced similar improvements in FMD: + 3.2% (95%CI 1.7, 4.6) (p < 0.001) in AT; + 4.0% (95%CI 2.1, 5.7) (p < 0.001) in RT; and +6.8% (95%CI 2.6, 11.1) (p = 0.006) in CT. In conclusion, different exercise training modalities were similarly effective in improving endothelial function but impacts on ambulatory blood pressure appear to be variable in individuals with prehypertension or hypertension.

Aims: We assessed the effects of a short-term exercise training on cardiac function, oxidative stress markers, and type 3 iodothyronine deiodinase (D3) activity in cardiac tissue of spontaneously hypertensive rats (SHR) following experimental myocardial infarction (MI)., Methods: Twenty-four SHR (aged 3 months) were allocated to 4 groups: sham+sedentary, sham+trained, MI+sedentary and MI+trained. MI was performed by permanent ligation of the coronary artery. Exercise training (treadmill) started 96 hours after MI and lasted for 4 weeks (~60% maximum effort, 4x/week and 40 min/day). Cardiac function (echocardiography), thioredoxin reductase (TRx), total carbonyl levels, among other oxidative stress markers and D3 activity were measured. A Generalized Estimating Equation was used, followed by Bonferroni's test (p<0.05)., Results: MI resulted in an increase in left ventricular mass (p = 0.002) with decreased cardiac output (~22.0%, p = 0.047) and decreased ejection fraction (~41%, p = 0.008) as well as an increase in the carbonyl levels (p = 0.001) and D3 activity (~33%, p<0.001). Exercise training resulted in a decrease in left ventricular mass, restored cardiac output (~34%, p = 0.048) and ejection fraction (~20%, p = 0.040), increased TRx (~85%, p = 0.007) and reduced carbonyl levels (p<0.001) and D3 activity (p<0.001)., Conclusions: Our short-term exercise training helped reverse the effects of MI on cardiac function. These benefits seem to derive from a more efficient antioxidant response and lower D3 activity in cardiac tissue., Competing Interests: The authors declare that they have no competing interests and each one read and approved the contents of the manuscript.

We assessed cardiac function (echocardiographic) and glucose transporter 4 (GLUT4) expression (Western blot) in response to 10 weeks of aerobic training (treadmill) prior to acute myocardial infarction (AMI) by ligation of the left coronary artery in spontaneously hypertensive rats. Animals were allocated to sedentary+sham, sedentary+AMI, training+sham, and training+AMI. Aerobic training prior to AMI partially preserves heart function. AMI and/or aerobic training increased GLUT4 expression. However, those animals trained prior to AMI showed a greater increase in GLUT4 in cardiomyocytes.

Elevated serum retinol binding protein 4 (RBP4) levels were previously described in insulin-resistance states. Exercise training can improve insulin sensitivity and RBP4, but the time-response effect of exercise detraining on RBP4 has not been studied. Thus, we examined the effects of exercise training and short-term detraining on insulin resistance, serum RBP4 levels, and GLUT4 expression in spontaneously hypertensive rats (SHR). Thirty-two male SHR, 4 months old, were submitted to 10-week treadmill training, 5 times/week or kept sedentary, followed by a 2- and 4-day detraining period. Body weight, insulin tolerance test, maximum speed in a maximal exercise test, serum RBP4 (ELISA), and epididymal fat GLUT4 expression (Western blot) were measured. Although all rats gained weight (43%, p=0.004) only the trained group showed a reduction (p<0.001) of epididymal fat weight. Detraining did not change these parameters. Exercise training increased insulin sensitivity (26%, p=0.001) and maximum exercise capacity (80%, p<0.001), benefits not lost after detraining. RBP4 levels were reduced in response to exercise training (45%, p<0.001); detraining did not change these benefits. Trained rats had increased GLUT4 expression (microsomal, ~226%; p<0.001 and plasma membrane, ~55%; p=0.011). A slight reduction in GLUT4 expression in the plasma membrane (~28%, p=0.041), but not in the microsomal fraction, was observed after 4 days of detraining. Exercise training is associated with reduced RBP4 levels, increased insulin sensitivity, and epididymal fat GLUT4 expression. Even short periods of detraining (4 days) were shown to be associated with reversal of higher plasma membrane GLUT4., (© Georg Thieme Verlag KG Stuttgart · New York.)

The adaptations of the human body resulting from the aging process especially loss of flexibility can increase the risk of falls and the risk of developing other health conditions. Exercise training, in particular the Pilates exercise method, has become an important form of physical activity that minimizes the deleterious effects of aging on flexibility. Few studies have evaluated the effect of this training method on body flexibility among elderly. We aimed to evaluate the effects of physical training using the Pilates method on body flexibility of elderly individuals. Eighteen elderly women and two elderly men (aged 70 ± 4 years) followed a 10-week Pilates training program. Individuals were recruited from the local community via open invitations. At study entry, none of them had limited mobility (walking requiring the use of walkers or canes). Furthermore, those with neurologic, muscular, or psychiatric disorders as well as those using an assistive device for ambulation were excluded secondary to limited participation. Flexibility assessment tests (flexion, extension, right and left tilt, and right and left rotation of the cervical and thoracolumbar spine; flexion, extension, abduction, and lateral and medial right and left rotation of the glenohumeral joint; flexion, extension, abduction, adduction, and lateral and medial rotation of the right and left hip; and flexion of the right and left knee) were performed by a blinded evaluator using a flexometer before and after the training period. All assessments were carried out at the same time of day. There was an observed increase in flexion (22.86%; p < 0.001), extension (10.49%; p < 0.036), and rotation to the left side (20.45%; p < 0.019) of the cervical spine; flexion (16.45%; p < 0.001), extension (23.74%; p = 0.006), lateral bending right (39.52%; p < 0.001) and left (38.02%; p < 0.001), and right rotation (24.85%; p < 0.001) and left (24.24%; p < 0.001) of the thoracolumbar spine; flexion (right--8.80%, p = 0.034; left--7.03%, p = 0.050), abduction (right--20.69%, p < 0.001; left--16.26%, p = 0.005), and external rotation (right--116.07% and left--143%; p < 0.001 for both directions) of the glenohumeral joint; flexion (right--15.83%, p = 0.050; left--9.55%, p = 0.047) of the hips; and bending (right--14.20%, p = 0.006; left--15.20%, p = 0.017) the knees. The joint with the greatest magnitude of improvement was the thoracolumbar spine. Thus, this type of training may minimize the deleterious effects of aging and may improve the functionality of elderly individuals, which would reduce the likelihood of accidents (especially falls).