Insulin in combination with pioglitazone prevents advanced cachexia in 256-Walker tumor-bearing rats: effect is greater than treatment alone and is associated with improved insulin sensitivity.

BACKGROUND: Insulin (INS) resistance and hypoinsulinemia commonly observed in cancer-carrying, can contribute to cachexia. However, the effects of INS and INS sensitizers, such as pioglitazone (PIO), particularly when used in combination therapy, on cancer cachexia have not been evaluated sufficiently. We investigated the effects of INS and PIO, at various doses, either isolated or combined, on cachexia in Walker-256 tumor-bearing rats (TB rats). METHODS: INS or INS + PIO were administered in TB rats, for 6 or 12 days, starting from the day of tumor cells inoculation. RESULTS: INS at 18 or 27 U/kg (12-days treatment), but not 9 U/kg, reduced fat loss and slightly prevented weight loss. However, INS 18 U/kg + PIO 5, 10, 20, or 40 mg/kg (6 or 12-day treatment) reduced fat loss and markedly prevented weight loss but did not affect muscle wasting. While TB rats lost weight (37.9% in 12 days), TB rats treated with INS 18 U/kg + PIO 5 mg/kg showed pronounced weight gain (73.7%), which was greater than the sum (synergism) of the weight gains promoted by isolated treatments with INS 18 U/kg (14.7%) or PIO 5 mg/kg (13.1%). The beneficial effect of the INS 18 U/kg + PIO 5 mg/kg on weight loss was associated with improved INS sensitivity, as indicated by the higher blood glucose clearance constant (kITT), decreased levels of free fatty acids and triacylglycerols (INS resistance-inducing factors) in the blood, and increased expression of p-Akt (INS signaling pathway protein) in adipose tissue. CONCLUSIONS: The combined treatment with INS 18 U/kg + PIO 5 mg/kg was more effective in preventing advanced cachexia in TB rats than each treatment alone, emerging as the best approach, considering the lower dosage and higher efficacy. This combination completely preserved adipose mass and markedly reduced weight loss through a synergistic mechanism linked to improved insulin sensitivity. These findings provide new insights into the importance of drug combinations in effectively combating fat loss in advanced cachexia.

The effectiveness of high-intensity interval training on body composition of rodent models of obesity: A systematic review and meta-analysis.

The present systematic review was compiled to analyze the effectiveness of High-intensity interval training (HIIT) protocols on the body composition of rodents with obesity. Databases were searched until February 2021 for experimental trials in rodents with a minimum duration of four weeks of HIIT and endpoints associated with obesity. The data were analyzed by meta-analysis performed for comparisons of body composition. Sensitivity analysis was performed to investigate the consistency of individual researches. Of all of the 524 studies found, only 14 were included. The analysis showed a significant reduction in body weight ([CI 95%: -8.35; -1.98] P ≤ 0.01), adiposity index ([IC 95%: -1.04; -0.80] P ≤ 0.01), and fat pads ([IC 95%: -0.59; -0.06] P ≤ 0.01). HIIT performed on treadmill or water was effective to reduce body weight (P < 0.05). In conclusion, HIIT attenuated both body weight and adiposity induced either by HFD (high-fat diet) or by GOM (genetic obese model), thereby inducing positive changes in body composition.

Effects of exercise modality and intensity on the CD4 count in people with HIV: a systematic review and meta-analysis.

The purpose of this study was to assess the effect of training modality and exercise intensity on the modulation of lymphocytes CD4 count in people living with HIV (PLWH). A search for randomised controlled trials was performed using five databases (PubMed/Medline, Cochrane, LILACS, Scielo and CAPES). Meta-analyses of mean differences (MD) were conducted using a random-effects model to compare the effects of training modality and intensity on CD4 count. The CD4 count comparing physical training vs. control group (MD of CD4 was 54.58 cell/ml³ [CI 95% 15.58-93.59], p =< 0.01). In according to the subgroup analysis, only aerobic exercise has proved to have a significant effect on CD4 (MD 79.91 cell/ml³ [CI 95% 19.30-140.52], p =< 0.01). When exercise intensities were stratified, only intense training proved to have a significant effect on CD4 (MD 64.87 cell/ml³ [CI 95% 15.79-113.95], p =< 0.01). In meta-regression analysis showed that the aerobic training, as well, high the intensity training were predictors significant to the improvement of CD4 (p =< 0.01). Exercise training is an important strategy to assist in the treatment of PLWH. The aerobic training modality and the high intensity training were able to promote improve the modulation of CD4 count chronically in PLWH.

Are rating of perceived exertion and heart rate methods useful to monitor the internal training load in functional training?

Abstract Aim: The study aimed to quantify and characterize the Training Load (TL) in a Functional Training (FT) model using Heart Rate (HR) and Session Rating of Perceived Exertion (sRPE) methods, and to verify whether these methods could be valid to monitor the TL during a FT program. Methods: The study design consisted of two phases: phase 1 - composed of a single training session of FT (FTSESSION), in which HR, sRPE, and pre- and post-exercise lactate [La] levels were assessed; phase 2 - composed of a FT program (FTPROGRAM) with eight weeks of duration and two sessions per week. The HR and SRPE were utilized to monitor all training sessions, and the results between sessions 1 vs. 8, 8 vs. 9, and 9 vs. 16 were compared. Results: On phase 1, HR distribution demonstrated that the participants spent about 75% of the total training time above 80% HRmax. Post-exercise [La] values were significantly higher (p < 0.05) than pre-exercise. The mean sRPE score was 8.5 ± 1.2. In phase 2, HR distribution was different between sessions 1-8 and 8-9 (p < 0.05). A strong correlation (r = 0.790) between the internal training load (ITL) and Training impulse (TRIMP) was observed. Conclusion: Our data demonstrated that the FTSESSION can be characterized as a high-intensity exercise, based on the pattern of HR responses and sRPE, and was reinforced by the [Lapeak]. Also, the TL monitoring methods (sRPE and TRIMP) proved to be valid for monitoring FT programs.

Resistance exercise training induces subcutaneous and visceral adipose tissue browning in Swiss mice.

Aerobic exercise training (AER) may promote several adaptations in white adipose tissue (WAT), including a phenotypic change known as browning. The present study aimed at assessing if resistance exercise training (RES) would be as efficient as AER in inducing a brown-like adipocyte reprogramming in WAT. Thirty Swiss male mice were randomly divided into 3 groups with 10 animals each: 1) sedentary (SED), 2) AER, and 3) RES. After the adaptation training, an incremental test was performed at the beginning of each week to adjust training load. Mice were submitted to 8 wk of AER or RES. After the experimental period, inguinal and retroperitoneal WAT (iWAT and rpWAT) and brown adipose tissue (BAT) were collected. The prescription of AER and RES was effective in increasing the performance of both groups. Also, RES presented a lower body weight than AER/SED. AER and RES reduced the area of iWAT and rpWAT adipocytes and the lipid area of BAT, induced an increase of vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) and uncoupling protein 1 (UCP-1), and increased the expression of selective genes of brown and beige phenotype in adipocytes after 8 wk. In general, we demonstrated here that AER and RES training similarly induced the browning of iWAT and rpWAT.NEW & NOTEWORTHY Aerobic exercise training (AER) induces the browning of white adipose tissue, turning adipocytes multilocular, highly vascularized and expressing uncoupling protein 1 (UCP-1). The current study compared the efficiency of resistance to aerobic exercise training to promote a brown-like phenotype. Our results suggest that both types of training similarly induce subcutaneous and visceral adipose tissue browning.

LLC tumor cells-derivated factors reduces adipogenesis in co-culture system.

Cancer cachexia (CC) is a multifactorial syndrome with an unknown etiology. The primary symptom is the progressive reduction of the body weight. Recently, down-regulation of adipogenic and lipogenic genes were demonstrated to be early affected during cachexia progression in adipose tissue (AT), resulting in AT remodeling. Thus, this study aimed to evaluate in a co-culture system the influence of the Lewis Lung Carcinoma (LLC) tumor cells (c/c-LLC) in an established pre-adipocyte cell line 3T3-L1 adipogenic capacity. c/c-LLC in the presence of 3T3-L1 caused a reduction in lipids accumulation, suggesting that secretory tumor cells products may affect adipogenesis. Interestingly, a very early (day 2) down-regulation of proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), followed by late genes (day 4 and 8), adiponectin, perilipin, and fatty acid-binding protein 4 (FABP4). Caspase-3 expression was increased on the last day of cell differentiation; it occurred in the expression of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Overall, our results suggest that LLC secretory products impair adipocyte differentiation in a co-culture system and increased apoptosis. In summary, our study has shown the inhibition of the adipogenic process in the 3T3-L1 co-culture system with LLC cells.

Effect of combined training on body composition and metabolic variables in people living with HIV: A randomized clinical trial.

PURPOSE: The aim of this study was to conduct a randomized clinical trial to assess the effects of 16 weeks of combined training on body composition, lipid profile, adiponectin, C-reactive protein (CRP), and leptin levels in people living with HIV/AIDS (PLWHA). METHODS: Fifty-eight HIV-infected individuals were randomized into a training group (T) or a control group (C). Combined training consisted of aerobic and resistance exercises performed at the same training session, applied at a frequency of three times a week for a total of 16 weeks. Waist circumference, body mass, body fat percentage (%fat), fat mass, lipid profile, adiponectin, CRP, and leptin levels were measured pre- and post-training in both groups. RESULTS: Sixteen weeks of combined training decreased (P < 0.05) body fat in different body segments in PLWHA. Lipodystrophic PLWHA experienced greater reduction in body fat in the android region than non-lipodystrophic PLWHA after combined training. Lipid profile and circulating levels of adiponectin, leptin, and CRP remained unchanged. CONCLUSIONS: Sixteen weeks of combined training was effective to reduce body fat in different body segments, without altering plasma lipid and cytokine levels.

Aerobic exercise training performed by parents reduces mice offspring adiposity.

The present study aimed to determine the effects of physical training performed by parents on mice offspring adiposity. Male and female parents underwent an aerobic training protocol for 7 weeks. The trained and sedentary parents were allowed to mate and the resultant offspring divided in: S (Offspring from Sedentary Parents), T (Offspring from Trained Parents), ST (Offspring from Sedentary Father and Trained Mother) and TS (Offspring from Trained Father and Sedentary Mother). After weaning, offspring was euthanized, blood collected and samples of mesenteric and inguinal fat pads used to isolate adipocytes for morphologic and histological analyses. Lee index, mesenteric fat pad, sum of visceral fat and total fat weight of female T was reduced in comparison to the other groups (p < 0.05). Periepididymal and sum of visceral fat in male T group was also reduced when compared to the other groups (p < 0.05). The diameter of mesenteric and inguinal adipocytes of T group was smaller compared to all groups comparisons for both sexes (p < 0.05). In summary, exercise training performed by parents reduced visceral offspring adiposity, the diameter of subcutaneous adipocytes and improved metabolic parameters associated to metabolic syndrome.

Exercise improves cytokine profile in HIV-infected people: A randomized clinical trial.

PURPOSE: Verify the effects of concurrent training on cytokines in people living with HIV under antiretroviral therapy (ART) treatment. METHODS: This was a blinded, parallel-group, clinical trial, where 49 participants, divided in two groups, either control group or concurrent training group, took part in the intervention. The control group performed recreational activities and concurrent training group participated of 16-week, 3 times per week of heart rate guided-aerobic plus resistance training for major muscular groups. Cytokines (interleukins 4, 5, 6, 8, 10, tumor necrosis factor-α, interferon-γ, and granulocyte-macrophage colony-stimulating factor) were measured before and after 16-week experimental period using flow cytometry. RESULTS: From 49 participants who took part in the intervention, 28 completed the program and had data analyzed. There was a significant interaction for IL-8, which increased for control group: 7.1±5.1 vs. 8.1±6.0 and a decrease for concurrent training: 8.0±4.4 vs. 5.4±2.3. In addition, magnitude-based inference showed a likely beneficial effect for the training group when compared to the control group for IL-8, IL-5, and IL-10. The difference perceptual: mean and [CI 90%] between delta of difference within groups was -43.1 [-64.0 to -10.0] and -6.6 [-14.7 to 2.3], respectively. CONCLUSION: Short-term exercise is able to decrease the levels of IL-5, IL-8, and IL-10 in HIV-infected people undergoing ART.

RESPOSTAS AGUDAS DO EXERCÍCIO FÍSICO EM PESSOAS INFECTADAS PELO HIV: UMA REVISÃO SISTEMÁTICA / ACUTE RESPONSES OF PHYSICAL EXERCISE IN PEOPLE INFECTED BY HIV: A SYSTEMATIC REVIEW / RESPUESTAS AGUDAS AL EJERCICIO FÍSICO EN PERSONAS INFECTADAS POR EL VIH: UNA REVISIÓN SISTEMÁTICA

RESUMO O treinamento físico é uma estratégia importante para a saúde de pessoas que vivem com HIV/AIDS; contudo, suas respostas a curto prazo ainda não foram amplamente estudadas, o que limita o entendimento dos efeitos e da segurança da prescrição do treinamento para essa população. Portanto, objetivou-se revisar sistematicamente as respostas agudas decorrentes do exercício físico em pessoas com HIV sobre variáveis fisiológicas e imunológicas. Para isso, foi realizada uma revisão sistemática a partir de trabalhos indexados nas seguintes bases de dados: Medline, Lilacs, Scielo, Web of Science e Science Direct. Os descritores utilizados foram: acquired immunodeficiency syndrome, HIV, AIDS, seropositive, acute session, short, physical activity, exercise, training. As buscas foram realizadas em fevereiro de 2015 e atualizadas em dezembro de 2015 e foram conduzidas sem restrição de datas de publicação ou idioma específico. Foram incluídos para esta revisão artigos que avaliaram as respostas agudas decorrentes de algum modelo de prescrição de treinamento físico envolvendo exercícios aeróbicos, com pesos ou combinados (exercícios aeróbicos e com pesos) relacionados com variáveis fisiológicas e imunológicas em pessoas infectadas pelo HIV. Foram encontrados 2.422 títulos, dos quais, após exclusão das duplicatas e a aplicação dos critérios de elegibilidade, foram selecionados sete artigos para síntese qualitativa. De acordo com os resultados reportados pelos estudos há evidências de que, imediatamente após a realização do exercício físico, ocorre um aumento do número de células circulantes, incluindo leucócitos totais, neutrófilos, monócitos e linfócitos T CD8+ em pessoas infectadas pelo HIV. Além disso, também se observaram alterações significantes nas concentrações de lactato, triglicerídeos, epinefrina e norepinefrina imediatamente após a realização do treinamento aeróbico, independentemente do uso de TARV e/ou de hiperlactatemia. No entanto, não há evidências suficientes para afirmar que o treinamento físico seja totalmente seguro e eficaz para esta população.

ABSTRACT Physical training is an important strategy for the health of people living with HIV/aids; however, its short-term responses have not yet been extensively studied, which limits the understanding of the effects and safety training prescription for this population. Therefore, we aimed to systematically review the acute responses resulting from physical exercise in people with HIV on physiological and immunological variables. For this, a systematic review was carried out from works indexed in the following databases: Medline, Lilacs, Scielo, Web of Science and Science Direct. The keywords used were acquired immunodeficiency syndrome, HIV, AIDS, seropositive, acute session, short, physical activity, exercise, training. The searches were conducted in February 2015 and updated in December 2015 and were conducted without restriction of publication dates or specific language. We included for this review articles that evaluated the acute responses derived from some model of prescription of physical training involving aerobic, weight or combined exercises (aerobic and weight exercises) related to physiological and immunological variables in HIV infected individuals. We found 2,422 titles of which, after exclusion of the duplicates and the application of the eligibility criteria, seven articles were selected for qualitative synthesis. According to the results reported by the studies, there is evidence that immediately after physical exercise an increase in the number of circulating cells occurs, including total leukocytes, neutrophils, monocytes and T CD8+ lymphocytes in HIV-infected people. Furthermore, significant changes in the concentrations of lactate, triglycerides, epinephrine and norepinephrine were also observed immediately after aerobic training regardless the use of HAART and/or hyperlactatemia. However, there is insufficient evidence to state that physical training is totally safe and effective for this population.

RESUMEN El entrenamiento físico es una estrategia importante para la salud de las personas que viven con el VIH/SIDA. Sin embargo, sus respuestas a corto plazo no han sido ampliamente estudiadas, lo que limita la comprensión de los efectos y la seguridad de la prescripción de entrenamiento para esta población. Por lo tanto, el objetivo fue revisar sistemáticamente las respuestas agudas al ejercicio en personas con VIH en las variables fisiológicas e inmunológicas. Para esto, se realizó una revisión sistemática de artículos indexados en las siguientes bases de datos: Medline, Lilacs, Scielo, Web of Science y Science Direct. Los descriptores utilizados fueron: acquired immunodeficiency syndrome, HIV, AIDS, seropositive, acute session, short, physical activity, exercise, training. Las búsquedas se realizaron en febrero de 2015 y fueron actualizadas en diciembre de 2015, siendo llevadas a cabo sin restricciones de fecha de publicación o idioma específico. Se seleccionaran en esta revisión los artículos que evaluaron las respuestas agudas de algún modelo de entrenamiento físico que implica la prescripción de ejercicios aeróbicos, con pesas o combinados (práctica de ejercicio aeróbico y pesas) relacionadas con variables fisiológicas e inmunológicas en las personas con VIH. Se encontraron 2.422 títulos, de los cuales, después de la exclusión de duplicados y la aplicación de los criterios de elegibilidad, se seleccionaron siete artículos para síntesis cualitativa. De acuerdo con los resultados reportados por estudios hay pruebas de que inmediatamente después del ejercicio hay un aumento en el número de células circulantes, incluyendo leucocitos totales, neutrófilos, monocitos y linfocitos T CD8+ en individuos infectados por el VIH. Además, se observaron cambios significativos en las concentraciones de lactato, triglicéridos, epinefrina y norepinefrina inmediatamente después del entrenamiento aeróbico, independientemente del uso de HAART y/o hiperlactatemia. Sin embargo, no hay pruebas suficientes para afirmar que el entrenamiento físico es completamente seguro y eficaz para esta población.

Effects of anabolic steroid treatment associated with physical training in adipose tissue of male Wistar rats / Efeito do tratamento com anabolizante associado com atividade física no tecido adiposo de ratos machos Wistar

Anabolic androgenic-steroids (AAS) include a broad class of synthetic derivatives of testosterone, being nandrolone decanoate the most widely used in sports environment. The aim of this study was to evaluate the metabolic effects of nandrolone decanoate in sedentary and trained adult male rats. We established four experimental groups: sedentary control, sedentary treated, trained control and trained treated. The training had consisted of running on a treadmill for nine weeks. Treated animals received intramuscular injections of nandrolone decanoate (0.5 mg kg-1) during the last four weeks of physical training. The training time as the drug used were not sufficient to significantly reduce body weight gain, but caused a significative decrease on diameter of adipocytes and in the amount of adipose tissue stored, as well as decreased the plasma levels of glucose and total cholesterol.

Os esteróides anabólicos androgênios incluem uma ampla classe de derivados sintéticos da testosterona, sendo o decanoato de nandrolona um dos mais utilizados no meio esportivo. Este trabalho teve como objetivo avaliar os efeitos metabólicos desse anabolizante esteróide em ratos machos adultos sedentários e treinados. Foram estabelecidos quatro grupos experimentais: sedentário controle, sedentário tratado, treinado controle e treinado tratado. O treinamento consistiu de corrida em esteira ergométrica durante nove semanas. Os animais tratados receberam injeção intramuscular de decanoato de nandrolona (0.5 mg kg-1) durante as quatro últimas semanas de treinamento físico. Tanto o tempo de treinamento, quanto a dose de anabolizante utilizado não foi eficiente para reduzir significativamente o ganho de peso corporal, mas causou reduções significativas no diâmetro dos adipócitos e na quantidade de tecido adiposo armazenado, assim como diminuiu os valores plasmáticos de glicose e de colesterol total.

Testis morphophysiology of rats treated with nandrolone decanoate and submitted to physical training / Morfofisiologia testicular de ratos tratados com decanoato de nandrolona e submetidos ao treinamento físico

The mammalian testis is a complex organ with endocrine and exocrine functions. It consists of seminiferous tubules where the production of the male gametes called spermatogenesis occurs. This process is influenced by a number of factors including the use of physical performance-enhancing drugs. The objective of this study was to evaluate the effects of the anabolic steroid nandrolone decanoate on the morphofunctional structure of testes in sedentary rats and rats subjected to moderate aerobic exercise training. Twenty-four male rats were divided into four experimental groups: sedentary control, sedentary treated, trained control and trained treated.The training lasted eight weeks and consisted of running on a programmable ergometer treadmill, tailored to train eight rats simultaneously. Treated animals received intramuscular injections of nandrolone decanoate (0.5 mg kg-1 body weight) during the last four weeks of physical training, while the control groups received intramuscular injections of vehicle (vegetable oil).The male reproductive system morphology showed that treatment with nandrolone decanoate, in both sedentary and trained rats, promoted morphological and functional changes that result in reduced efficiency of spermatogenesis.

O testículo de mamíferos é um órgão complexo com funções endócrinas e exócrinas. É composto por túbulos seminíferos, local onde ocorre a espermatogênese, processo de produção dos gametas masculinos. Este processo é influenciado por uma série de drogas potencializadoras do desempenho físico, que são utilizadas para melhorar a performance. O objetivo deste estudo foi avaliar os efeitos do anabolizante esteróide decanoato de nandrolona sobre a estrutura morfofuncional de testículos de ratos sedentários e submetidos ao treinamento físico aeróbico moderado. Foram utilizados vinte e quatro ratos machos divididos em quatro grupos experimentais: sedentário controle, sedentário tratado, treinado controle e treinado tratado. O treinamento teve duração de oito semanas e consistiu de corrida em esteira ergométrica programável, adaptada para treinar oito ratos simultaneamente. Os grupos tratados receberam injeção intramuscular de decanoato de nandrolona (0,5 mg kg -1) durante as quatro últimas semanas de treinamento físico, enquanto os grupos controles receberam injeção intramuscular do veículo (óleo vegetal). Os resultados mostraram que o tratamento com o decanoato de nandrolona, tanto em ratos sedentários como submetidos ao exercício físico, promove alterações morfofuncionais que resultam na redução da eficiência da espermatogênese.

Use of the anabolic steroid nandrolone decanoate associated to strength training in Wistar rats / Uso do esteróide anabólico decanoato de nandrolona associado ao treinamento de força em ratos Wistar

Anabolic steroids have been constantly used among athletes and physically active individuals. Adverse effects of such use are reported in the literature. However, little is known about the effects of anabolic steroid use associated with strength training. Thus, this research aimed to identify possible morphophysiological alterations in Wistar rats treated with the anabolic steroid nandrolone decanoate and submitted to strength training. Twenty Wistar rats were divided in four groups: sedentary control (SC), sedentary hormone (SH), trained control (TC) and trained hormone (TH). After the experimental protocol period, animals were killed and body weight, adiposity, renal and hepatic injury markers, plasmatic lipid profile, glycemia, and insulinemia were determined. The experimental conditions strength training and nandrolone decanoate (isolated or associated) were positively correlated to a reduction on visceral and subcutaneous adipose tissue. The association of strength training with nandrolone decanoate was the most effective condition to increase muscle mass. Heart and kidneys weights, aspartate aminotransferase (AST) and high density lipoprotein (HDL) concentration were also negatively modified. The data demonstrated effects of anabolic steroids in body composition, with better results when associated with strength training, but collateral effects were observed.

Os esteróides anabólicos são usados indiscriminadamente entre atletas e praticantes de atividades físicas sendo que os efeitos adversos desse uso constam na literatura. Contudo, pouco se sabe dos efeitos do uso de esteróides anabólicos associados ao treinamento de força. Assim, este estudo objetivou identificar possíveis alterações morfofisiológicas em ratos Wistar tratados com decanoato de nandrolona e submetidos ao treinamento de força. Para atingir tal propósito, vinte ratos Wistar foram divididos em quatro grupos: sedentário controle (SC), sedentário hormônio (SH), treinado controle (TC) e treinado hormônio (TH). Após o período experimental, foram analisados o peso corporal, a adiposidade, marcadores de lesões hepáticas e renais, o perfil lipídico, a glicemia e a insulinemia. Foram observados efeitos do treinamento de força e do uso de decanoato de nandrolona (isolados ou associados) nos tecidos adiposos viscerais e subcutâneo. A associação de treinamento de força e uso de decanoato de nandrolona foi mais efetiva para aumentar a massa muscular. Os pesos dos rins e coração, e concentrações de aspartato aminotransferase (AST) e lipoproteína de alta densidade (HDL) foram negativamente modificados. Os dados demonstram efeitos do esteróide anabólico sobre a composição corporal, com melhores resultados obtidos com a associação ao treinamento de força, contudo efeitos colaterais foram observados.

Creatine supplementation in trained rats causes changes in myenteric neurons and intestinal wall morphometry.

Creatine is widely used by athletes as an ergogenic resource. The aim of this study was to evaluate the influence of creatine supplementation on the duodenum of rats submitted to physical training. The number and myenteric neuronal cell bodies as well mucosal and muscular tunic morphometry were evaluated. Control animals received a standard chow for 8 weeks, and the treated ones received the standard chow for 4 weeks and were later fed with the same chow but added with 2% creatine. Animals were divided in groups: sedentary, sedentary supplemented with creatine, trained and trained supplemented with creatine. The training consisted in treadmill running for 8 weeks. Duodenal samples were either processed for whole mount preparations or for paraffin embedding and hematoxylin-eosin staining for histological and morphometric studies of the mucosa, the muscular tunic and myenteric neurons. It was observed that neither creatine nor physical training alone promoted alterations in muscular tunic thickness, villus height or crypts depth, however, a reduction in these parameters was observed when both were associated. The number of myenteric neurons was unchanged, but the neuronal cell body area was reduced in trained animals but not when training and creatine was associated, suggesting a neuroprotector role of this substance.

Creatine supplementation in trained rats causes changes in myenteric neurons and intestinal wall morphometry. / Creatine supplementation in trained rats causes changes in myenteric neurons and intestinal wall morphometry.

Creatine is widely used by athletes as an ergogenic resource. The aim of this study was to evaluate the influence of creatine supplementation on the duodenum of rats submitted to physical training. The number and myenteric neuronal cell bodies as well mucosal and muscular tunic morphometry were evaluated. Control animals received a standard chow for 8 weeks, and the treated ones received the standard chow for 4 weeks and were later fed with the same chow but added with 2

creatine. Animals were divided in groups: sedentary, sedentary supplemented with creatine, trained and trained supplemented with creatine. The training consisted in treadmill running for 8 weeks. Duodenal samples were either processed for whole mount preparations or for paraffin embedding and hematoxylin-eosin staining for histological and morphometric studies of the mucosa, the muscular tunic and myenteric neurons. It was observed that neither creatine nor physical training alone promoted alterations in muscular tunic thickness, villus height or crypts depth, however, a reduction in these parameters was observed when both were associated. The number of myenteric neurons was unchanged, but the neuronal cell body area was reduced in trained animals but not when training and creatine was associated, suggesting a neuroprotector role of this substance.

Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPbeta transcriptional activity.

Considering that melatonin has been implicated in body weight control, this work investigated whether this effect involves the regulation of adipogenesis. 3T3-L1 preadipocytes were induced to differentiate in the absence or presence of melatonin (10(-3) m). Swiss-3T3 cells ectopically and conditionally (Tet-off system) over-expressing the 34 kDa C/EBPbeta isoform (Swiss-LAP cells) were employed as a tool to assess the mechanisms of action at the molecular level. Protein markers of the adipogenic phenotype were analyzed by Western blot. At 36 hr of differentiation of 3T3-L1 preadipocytes, a reduction of PPARgamma expression was detected followed by a further reduction, at day 4, of perilipin, aP2 and adiponectin protein expression in melatonin-treated cells. Real-time PCR analysis also showed a decrease of PPARgamma (60%), C/EBPalpha (75%), adiponectin (30%) and aP2 (40%) mRNA expression. Finally, we transfected Swiss LAP cells with a C/EBPalpha gene promoter/reporter construct in which luciferase expression is enhanced in response to C/EBPbeta activity. Culture of such transfected cells in the absence of tetracycline led to a 2.5-fold activation of the C/EBPalpha promoter. However, when treated with melatonin, the level of C/EBPalpha promoter activation by C/EBPbeta was reduced by 50% (P = 0.05, n = 6). In addition, this inhibitory effect of melatonin was also reflected in the phenotype of the cells, since their capacity to accumulate lipids droplets was reduced as confirmed by the poor staining with Oil Red O. In conclusion, melatonin at a concentration of 10(-3 ) m works as a negative regulator of adipogenesis acting in part by inhibiting the activity of a critical adipogenic transcription factor, C/EBPbeta.

Melatonin and the circadian entrainment of metabolic and hormonal activities in primary isolated adipocytes.

The aim of this work was to investigate the effect of the in vitro circadian-like exposure to melatonin [in the presence or absence of insulin (Ins)] on the metabolism and clock gene expression in adipocytes. To simulate the cyclic characteristics of the daily melatonin profile, isolated rat adipocytes were exposed in a circadian-like pattern to melatonin added to the incubating medium for 12 hr (mimicking the night), followed by an equal period without melatonin (mimicking the day) combined or not with Ins. This intermittent incubation was interrupted when four and a half 24-hr cycles were fulfilled. At the end, either during the induced night (melatonin present) or the induced day (melatonin absent), the rates of lipolysis and D-[U-(14)C]-glucose incorporation into lipids were estimated, in addition to the determination of lipogenic [glucose-6-phosphate dehydrogenase and fatty acid synthase (FAS)] and lipolytic (hormone sensitive lipase) enzymes and clock gene (Bmal-1b, Clock, Per-1 and Cry-1) mRNA expression. The leptin release was also measured. During the induced night, the following effects were observed: an increase in the mRNA expression of Clock, Per-1 and FAS; a rise in lipogenic response and leptin secretion; and a decrease in the lipolytic activity. The intermittent exposure of adipocytes to melatonin temporally and rhythmically synchronized their metabolic and hormonal function in a circadian fashion, mimicking what is observed in vivo in animals during the daily light-dark cycle. Therefore, this work helps to clarify the physiological relevance of the circadian pattern of melatonin secretion and its interactions with Ins, contributing to a better understanding of the adipocyte biology.

Melatonin enhances leptin expression by rat adipocytes in the presence of insulin.

Leptin and melatonin play an important role in the regulation of body mass and energy balance. Both hormones show a circadian rhythm, with increasing values at night. In addition, melatonin receptors were recently described in adipocytes, where leptin is synthesized. Here, we investigated the influence of melatonin and its interaction with insulin and dexamethasone on leptin expression. Isolated rat adipocytes were incubated with melatonin (1 nM) alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) for 6 h. Melatonin or insulin alone did not affect leptin expression, but together they increased it by 120%. Dexamethasone increased leptin mRNA content (105%), and this effect was not enhanced by melatonin. Simultaneous treatment with the three hormones provoked a further increase in leptin release (250%) and leptin mRNA (100%). Melatonin prevented the forskolin-induced inhibition (95%) of leptin expression. In addition, melatonin's ability to stimulate leptin release (in the presence of insulin) was completely blocked by pertussis toxin and luzindole. To gain further insight into the molecular basis of melatonin and insulin synergism, the insulin-signaling pathway was investigated. Melatonin increased the insulin-induced insulin receptor-beta tyrosine phosphorylation, which led to an increased serine phosphorylation of the downstream convergent protein Akt. We concluded that melatonin interacts with insulin and upregulates insulin-stimulated leptin expression. These effects are caused by melatonin binding to the pertussis toxin-sensitive G(i) protein-coupled membrane receptor (MT1 subtype) and the cross talk with insulin, since insulin receptor and its convergent target Akt are coactivated by melatonin.

Pinealectomy alters adipose tissue adaptability to fasting in rats.

This study investigated the effects of pinealectomy and fasting on rat adipose tissue metabolism, as well as on profiles of the hormones directly involved in its regulation (insulin, leptin, and corticosterone). Pinealectomized (PINX) and sham-operated (CONTROL) adult male Wistar rats were killed 6 weeks after surgery, in either fed or fasted (12 and 36 hours) states. Blood samples (for glucose and hormone determinations) and peri-epididymal adipocytes (for in vitro insulin-stimulated glucose uptake, oxidation, and incorporation into lipids) were collected. Pineal ablation decreased insulin-stimulated glucose uptake in adipocytes of both fed and fasted animals without affecting insulin-binding capacity. Pinealectomy attenuated the reduction in the ability to oxidize glucose in both basal and insulin-stimulated states during fasting. This alteration in the ability of adipocytes to oxidize glucose appeared together with a decrease in insulin-induced glucose incorporation into lipids in PINX animals. Additionally, pinealectomized rats showed higher corticosterone levels in both fed and fasted states, and a lower leptinemia with 36 hours of fasting, in comparison to CONTROLs. In conclusion, our data reinforce the hypothesis that the pineal gland has a role in the modulation of adipocyte metabolism, and its absence alters metabolic adaptation to fasting in rats.

Influência de esteróide anabólico (deca-durabolin) sobre o metabolismo de ratos submetidos ao treinamento físico / Influence of anabolic steroid (deca-durabolin) on metabolism in rats submited to physical training

Os esteróides anabólicos têm sido descritos por aumentarem a massa muscular e o balanço nitrogenado positivo. Por outro lado, o treinamento físico aumenta as reservas de carboidratos, bem como a síntese de proteínas. O Objetivo deste traballio foi estudar a influência da deca-durabolin sobre o metabolismo em ratos submetidos ao treinamento físico. Os ratos foram distribuídos em sedentários nao tratados (SN); sedentários tratados (ST); treinados nao tratados (TN) e treinados tratados (TT). Os tratados receberam duas injeçoes subcutâneas por semana do decanoato de nandrolona (1 mg/kg p.c.) durante seis semanas. O programa de treinamento consistiu de nataçao com carga de 5 por cento do peso corporal, uma hora por dia, cinco dias por semana, durante seis semanas. Após o período experimental, os ratos foram sacrificados por decapitaçao, e o sangue e tecidos coletados para análises. Nao foram encontrados diferenças significativas nos níveis de glicose e proteínas circulantes. O grupo TT mostrou aumento no peso corporal e tecido adiposo epididimal. O glicogênio e proteínas no diafragma foi elevado nos grupos ST, TN e TT. Portanto, o esteróide anabolizante e a atividade física tiveram influências sobre o metabolismo de ratos Wistar.