The degree of food processing can influence serum fatty acid and lipid profiles in women with severe obesity.

Background: The increase in the prevalence of obesity is associated with the increase in the consumption of ultra-processed foods and may be related to the increase in the disorders involving metabolism and the transport and storage of fatty acids. Objective: To evaluate the effect of processed food consumption according to the degree of processing on the serum fatty acid levels and lipid profile of women with severe obesity. Methods: This was a cross-sectional study. Data were collected from anthropometric assessments, the food frequency questionnaire (FFQ), and blood tests for lipidogram studies and serum fatty acid measurements. The foods consumed were identified through the FFQ and classified according to the degree of processing based on the NOVA rating, and the frequencies of consumption were transformed into scores, as proposed by Fornés methodology. Data were analyzed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. Results: This study included 44 women with a mean age of 40.59 years and mean body mass index of 48.61 kg/m2. An inverse association was observed between the consumption of unprocessed and the occurrence of hypertriglyceridemia (p = 0.021) and levels of triglycerides (p = 0.047), total cholesterol (p = 0.030), and very low-density lipoprotein-cholesterol (p = 0.039). The consumption of processed foods was positively associated with the presence of hypertriglyceridemia (p = 0.044) and omega 6/3 ratio (p = 0.001) and negatively associated with total omega 3 levels (p = 0.011). The consumption of processed foods was positively associated with total cholesterol (p = 0.041) and negatively associated with the omega 3/6 ratio (p = 0.001). A negative correlation was found between the average consumption of ultra-processed foods (at least once a week) and serum level of high-density lipoprotein (p = 0.035). Conclusion: The consumption of processed and ultra-processed foods was associated with unfavorable lipid profiles and fatty acid levels in women with severe obesity. These results emphasize the importance of promoting the consumption of unprocessed food to mitigate metabolic disorders linked to processed food intake.

Body Weight Loss is not Different between Patients with Digestion Gastrointestinal and Accessory Organs Cancer With High or low Neutrophils to Lymphocytes Ratio / Perda de Peso Corporal não é Diferente Entre Pacientes com Câncer Gastrointestinal e de Órgãos Acessórios da Digestão com Alta ou Baixa Relação Neutrófilos/Linfócitos

This study sought to assess if patients with cancer with high neutrophils to lymphocytes ratio (NLR) leads to body weight loss. A crosssectional study was performed in a public hospital. A total of 97 patients with digestion gastrointestinal and accessory organs cancers were evaluated. Body mass index (kg/m2) was calculated using the body weight (kg) divided by square of height (m) and body weight loss was obtained by percentage of body weight loss in the last months. The systemic inflammation was measured using the NLR and ≥6.5 values were considered as a high inflammation. It was found out that 11.3% of the patients have NLR ≥6.5. The NLR group ≥6.5 was younger than the NLR group <6.5 (NLR ≥6.5: 51.7 ± 14.1 vs. NLR <6.5: 61.9 ± 11.9 y, p=0.01), but without differences among sex, alcohol consumption, smoking, physical activity, body weight, body weight loss percentage and body mass index. In conclusion, it was found out that patients with digestion gastrointestinal and accessory organs cancers with NLR ≥6.5 did not differ in body weight loss when compared to patients with NLR <6.5. (AU)

Este estudo procurou avaliar se pacientes com câncer com alta razão neutrófilos/linfócitos (RNL) apresentam maior perda de peso corporal. Foi realizado um estudo transversal em um hospital público. Foram avaliados total de 97 pacientes com cânceres gastrointestinais e de órgãos acessórios da digestão. O índice de massa corporal (kg/m2) foi calculado usando o peso corporal (kg) dividido pelo quadrado da altura (m) e a perda de peso corporal foi adquirida pela porcentagem de perda de peso corporal nos últimos meses. A inflamação sistêmica foi medida pelo RNL e valores ≥6,5 foram considerados como alta inflamação. Nós encontramos que 11,3% dos pacientes têm RNL ≥6,5. O grupo RNL ≥6,5 é composto de pacientes mais jovens do que o grupo RNL <6,5 (RNL ≥6,5: 51,7 ± 14,1 vs. RNL <6,5: 61,9 ± 11,9 anos, p=0,01), mas sem diferenças entre sexo, consumo de álcool, tabagismo, atividade física, peso corporal, porcentagem de perda de peso corporal e índice de massa corporal. Em conclusão, nós observamos que pacientes com cânceres gastrointestinais e de órgãos acessórios da digestão com RNL ≥6,5 não diferiram na perda de peso corporal quando comparados com pacientes com RNL <6,5. (AU)

Ursolic acid does not change the cytokine levels following resistance training in healthy men: A pilot balanced, double-blind and placebo-controlled clinical trial.

Ursolic acid (UA) is a natural compound that shows anti-inflammatory actions. However, no human studies have investigated the cytokine profile during the RT and UA consumption. The purpose of this study was to verify if UA is able to potentiate the anti-inflammatory activity after RT, reflecting in the reduction of blood inflammatory markers in healthy men. Twenty-seven participants were allocated to two groups: control (CON) (n = 13) and UA (n = 14). For 8weeks, each group performed RT and consumed capsules containing a placebo (400 mg/day) or UA (400 mg/day). Serum cytokine concentrations were evaluated before and after the training period. There was no difference in the serum cytokine concentrations of TNF-α, IL-10 and IL-6 (p > 0.05). In conclusion, UA supplementation for 8weeks was not able to change the blood TNF-α, IL-10, and IL-6 concentrations in healthy men undergoing RT. However, further studies are warranted to investigate other inflammatory markers.

Sodium Bicarbonate Supplementation Does Not Improve Running Anaerobic Sprint Test Performance in Semiprofessional Adolescent Soccer Players.

Ergogenic strategies have been studied to alleviate muscle fatigue and improve sports performance. Sodium bicarbonate (NaHCO3) has improved repeated sprint performance in adult team-sports players, but the effect for adolescents is unknown. The aim of the present study was to evaluate the effect of NaHCO3 supplementation on repeated sprint performance in semiprofessional adolescent soccer players. In a double-blind, placebo-controlled, crossover trial, 15 male semiprofessional adolescent soccer players (15 ± 1 years; body fat 10.7 ± 1.3%) ingested NaHCO3 or a placebo (sodium chloride) 90 min before performing the running anaerobic sprint test (RAST). A countermovement jump was performed before and after the RAST, and ratings of perceived exertion, blood parameters (potential hydrogen and bicarbonate concentration), and fatigue index were also evaluated. Supplementation with NaHCO3 promoted alkalosis, as demonstrated by the increase from the baseline to preexercise, compared with the placebo (potential hydrogen: +0.07 ± 0.01 vs. -0.00 ± 0.01, p < .001 and bicarbonate: +3.44 ± 0.38 vs. -1.45 ± 0.31 mmol/L, p < .001); however, this change did not translate into an improvement in RAST total time (32.12 ± 0.30 vs. 33.31 ± 0.41 s, p = .553); fatigue index (5.44 ± 0.64 vs. 6.28 ± 0.64 W/s, p = .263); ratings of perceived exertion (7.60 ± 0.33 vs. 7.80 ± 0.10 units, p = .525); countermovement jump pre-RAST (32.21 ± 3.35 vs. 32.05 ± 3.51 cm, p = .383); or countermovement jump post-RAST (31.70 ± 0.78 vs. 32.74 ± 1.11 cm, p = .696). Acute NaHCO3 supplementation did not reduce muscle fatigue or improve RAST performance in semiprofessional adolescent soccer players. More work assessing supplementation in this age group is required to increase understanding in the area.

Creatine supplementation does not promote additional effects on inflammation and insulin resistance in older adults: A pilot randomized, double-blind, placebo-controlled trial.

BACKGROUND: A chronic, low-grade inflammation is commonly present in older adults and has been associated with the onset of age-related chronic diseases. Resistance training (RT) and creatine (CR) supplementation emerged as promising strategies to reduce circulating pro-inflammatory cytokines. This study aimed to investigate the effects of CR supplementation combined with RT on markers of inflammation and insulin resistance in community-dwelling older adults. METHODS: In a pilot randomized, double-blind, placebo-controlled trial, participants were allocated to one of the following groups: 1) Creatine supplementation and resistance training (CR + RT, n = 13); 2) Placebo and resistance training (PL + RT, n = 14). While engaged in a 12-week RT program, participants from CR + RT group received 5 g/day of CR monohydrate and participants from PL + RT group received the same dose of maltodextrin. At baseline and at week 12, blood samples were collected for glucose, insulin, adiponectin, leptin, interleukin 6, interleukin 10, monocyte chemo-attractant protein-1 and C-reactive protein analysis. RESULTS: After 12 weeks of intervention, there were no differences between groups in any of the variables analyzed. Monocyte chemoattractant protein-1 was reduced in both groups (CR + RT: -55.66 ± 48.93 pg/mL, p < 0.01, dz = 1.13; PL + RT: -46.52 ± 55.21 pg/mL, p < 0.01, dz = 0.84). CONCLUSION: Resistance training, regardless of CR supplementation, decreased MCP-1 concentration in older adults.

Effects of turmeric extract supplementation on inflammation and muscle damage after a half-marathon race: a randomized, double-blind, placebo-controlled trial.

PURPOSE: Strenuous exercise induces inflammation and muscle damage. Turmeric (Curcuma longa L.) is a widely used spice that exhibits potent anti-inflammatory response and appears to decrease indirect markers of muscle damage. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the effects of Curcuma longa L. extract (CLE) on inflammation and muscle damage after a half-marathon race. METHODS: Twenty-eight healthy, normal-weight men were randomly assigned to one of two groups: (1) CLE (3 capsules per day, 500 mg each); or (2) placebo (PLA, 3 capsules per day, 500 mg of microcrystalline cellulose). Participants received the intervention for 4 weeks and immediately before and after the half-marathon race. Creatine kinase, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, myoglobin, interleukins 6 and 10 were assessed at baseline, immediately before, after, and at 2, 24, and 48 h after the half-marathon race. RESULTS: The half-marathon race increased markers of inflammation and muscle damage. A greater increase in interleukin-10 was observed in the CLE group immediately after the competition compared to the PLA group (7.54 ± 1.45 vs 5.25 ± 0.59 pg/mL; p < 0.05; d = 0.55). Myoglobin concentration was lower 2 h after the race in participants from the CLE group compared to the PLA group (62.10 ± 8.26 vs 107.85 ± 18.45 ng/mL; p = 0.01; d = 0.86). CONCLUSION: Curcuma longa L. extract supplementation leads to an increase in IL-10 and decreased myoglobin in recreational male runners after a half-marathon race. TRIAL REGISTRATION NUMBER: U1111-1179-6335, February 13, 2016.

Short-Term Creatine Supplementation May Alleviate the Malnutrition-Inflammation Score and Lean Body Mass Loss in Hemodialysis Patients: A Pilot Randomized Placebo-Controlled Trial.

BACKGROUND: Creatine supplementation has been proposed to alleviate muscle loss in various populations, but has not been investigated in hemodialysis (HD) patients. Thus, our objective was to evaluate whether creatine supplementation could attenuate the loss of lean body mass (LBM) and malnutrition-inflammation score (MIS) in HD patients. METHODS: A randomized, placebo-controlled, double blind, parallel-design study included HD patients, of both sexes, aged 18-59 years. The patients were allocated to a Placebo Group (PG; n = 15; received maltodextrin, 1st week: 40 g/day and 2nd-4th weeks: 10 g/day) and a Creatine Group (CG; n = 15; received creatine plus maltodextrin, 1st week: 20 g/day of creatine plus 20 g/day of maltodextrin and 2nd-4th weeks: 5 g/day of creatine plus 5 g/day of maltodextrin). Pre and post the intervention, patients were evaluated for food intake, MIS, body composition and biochemical parameters. RESULTS: CG group attenuated the MIS (Pre: 5.57 ± 0.72 vs. Post: 3.85 ± 0.47 score, P = 0.003) compared with PG (Pre: 5.71 ± 0.97 vs. Post: 5.36 ± 0.95 score, P = 0.317) (supplement × time P = 0.017, effect size: 0.964). The change of LBM was greater in CG than in PG (CG: Δ0.95 vs PG: Δ0.13 kg). At post-intervention, 28.6% of PG patients presented LBM loss and 71.4% remain stable. In contrast, 14.4% of CG patients had LBM loss, 42.8% remain stable and 42.8% gained. Food intake and quality of life did not change. CG increased the BMI and gait speed in post-compared to pre-moment, but no difference among the groups. CONCLUSION: In HD patients, four weeks of creatine supplementation may alleviate the MIS as well as attenuate the LBM loss compared to placebo.

Acute Caffeine and Coconut Oil Intake, Isolated or Combined, Does Not Improve Running Times of Recreational Runners: A Randomized, Placebo-Controlled and Crossover Study.

The aim was to evaluate the effect of caffeine (CAF) and extra virgin coconut oil (CO), isolated or combined, on running performance in runners. Methods: A randomized, placebo-controlled, and crossover study was conducted with thirteen recreational runners aged 18-40. All volunteers performed a 1600 m time trial at a 400 m track, each ingesting four different substances: (1) placebo (water), (2) decaffeinated coffee plus isolated CAF (DECAF + CAF), (3) decaffeinated coffee plus isolated CAF plus soy oil (DECAF + CAF + SO), and (4) decaffeinated coffee plus isolated CAF plus extra virgin coconut oil (DECAF + CAF + CO). The substances were ingested 60 min before the trials, the order of the situations was randomized, and there were one-week intervals between them. At the end of the trials, the Borg scale was applied to evaluate the rating of perceived exertion (RPE) and the time was measured. Results: Our data did not show differences in running time among the trials (placebo: 7.64 ± 0.80, DECAF + CAF: 7.61 ± 1.02, DECAF + CAF + SO: 7.66 ± 0.89, and DECAF + CAF + CO: 7.58 ± 0.74 min; p = 0.93), nor RPE (placebo: 6.15 ± 2.03, DECAF + CAF: 6.00 ± 2.27, DECAF + CAF + SO: 6.54 ± 2.73, and DECAF + CAF + CO: 6.00 ± 2.45 score; p = 0.99). Lactate concentrations (placebo: 6.23 ± 2.72, DECAF + CAF: 4.43 ± 3.77, DECAF + CAF + SO: 5.29 ± 3.77, and DECAF + CAF + CO: 6.17 ± 4.18 mmol/L; p = 0.55) also was not modified. Conclusion: Our study shows that ingestion of decaffeinated coffee with the addition of isolated CAF and extra virgin CO, either isolated or combined, does not improve 1600 m running times, nor influence RPE and lactate concentrations in recreational runners. Thus, combination of coffee with CO as a pre-workout supplement seems to be unsubstantiated for a short-distance race.

Effects of placebo on bench throw performance of Paralympic weightlifting athletes: a pilot study.

BACKGROUND: The aim of the present study was to analyse the effects of placebo on bench throw performance in Paralympic weightlifting athletes. METHODS: The study involved four Paralympic weightlifting male athletes (age: 40.25 ± 9.91 years, weight: 60.5 ± 8.29 kg, height: 1.60 ± 0.15 m) that visited the laboratory in three occasions, separated by 72 h. In the first session, the athletes were tested for bench press one repetition maximum (1RM). The other two sessions were performed in a randomized counter-balanced order and involved bench throw tests performed either after taking placebo while being informed that the capsule contained caffeine or without taking any substance (control). The bench throw tests were performed with loads corresponding to 50, 60, 70 and 80% of the bench press 1RM. RESULTS: According to the results, mean velocity (∆: 0.08 m/s, ES 0.36, p < 0.05) and mean propulsive velocity (∆: 0.11 m/s, ES 0.49, p < 0.05) at 50% of 1RM were significantly higher during placebo than control (p < 0.05). However, there were no difference between control and placebo for 60, 70 and 80% of 1RM (p > 0.05). CONCLUSION: Our results suggest that placebo intake, when the athletes were informed they were taking caffeine, might be an efficient strategy to improve the performance of explosive movements in Paralympic weightlifting athletes when using low-loads. This brings the possibility of using placebo in order to increase performance, which might reduce the risks associated with ergogenic aids, such as side-effects and positive doping testing.

Impact to short-term high intensity intermittent training on different storages of body fat, leptin and soluble leptin receptor levels in physically active non-obese men: A pilot investigation.

BACKGROUND & AIMS: Studies have postulated High Intensity Intermittent Training (HIIT) as a superior strategy to reduce body fat. The purpose of this study was to compare the effects HIIT and steady-state training (SST) on body composition, leptin, soluble leptin receptor (sOB-R) levels, and hunger perception in physically active non-obese men. METHODS: Twenty men performed five weeks of HIIT (5 km - 1 min running at 100% speed correspondent to VÈ©O2peak - v VÈ©O2peak - interspersed with 1-min passive recovery; n = 10) or SST (5 km at 70% of vVÈ©O2peak continuously; n = 10) three times a week. Body composition, and hunger perception were assessed at pre- and post-training and were compared by a two-way analysis (group and training period) with repeated measures in the second factor. A fasting time-course (baseline, 24 h, and 48 h after an experimental session of exercise) of leptin and sOB-R levels were measured at pre- and post-five weeks of training and assessed by a three-way analysis (group, period and time of measurement) with repeated measures in the second and third factors. RESULTS: There was no effect on body composition and hunger perception. Leptin was reduced in both groups, while sOB-R was increased post-five weeks of training in HIIT but not in the SST. CONCLUSIONS: Although both training groups exerted alterations in leptin levels, only HIIT was able increased sOB-R levels, this suggest a superior impact on central responses in physically active non-obese men.

Quality of Life Is Influenced by Body Weight, Education, and Family Income in Adolescents with Chronic Diseases.

OBJECTIVE: To evaluate the health-related quality of life (HRQoL) of adolescents diagnosed with different chronic conditions and to identify demographic, socioeconomic, and health-status outcomes associated with the impairment in HRQoL. STUDY DESIGN: Cross-sectional study. METHODS: We evaluated 276 adolescents (50.7% male) aged 14 ± 2 years that were assisted by healthcare public service and diagnosed with cancer (CA), type 1 diabetes mellitus (DM1), overweight (OW), asthma (AS), and no chronic health condition-control group (CG). Adolescents and parent-proxy completed age-appropriate self-report and/or parent-proxy report on generic HRQoL measures using PedsQL™. RESULTS: Adolescents with CA had lower overall HRQoL as well as poorer scores in all dimensions than either healthy participants or other chronic disease sufferers. HRQoL scores reported by parent-proxy were similar to those reported by adolescents across all chronic diseases. CG members reported better scores in all dimensions. Maternal education, family income, and marital status of parents were correlated with HRQoL scores in all dimensions. The risk of having an affected HRQoL score was higher in adolescents with CA than in adolescents with other chronic diseases. CONCLUSIONS: The likelihood of cancer affecting HRQoL was higher when compared to other chronic diseases, and the OW group had a worse overall score compared to CG. Adolescents with CA, AS, and OW reported worse school dimensions when compared to healthy adolescents. The education of adolescents and their parent-proxy, body weight, and family income influence the dimensions of HRQoL in adolescents with chronic diseases.

Low Handgrip Strength Is Not Associated with Type 2 Diabetes Mellitus and Hyperglycemia: a Population-Based Study.

Type 2 diabetes mellitus (DM) is commonly linked to muscle weakness and metabolic abnormalities which increase healthcare costs. The study was undertaken to investigate if low handgrip strength, as a marker of muscle weakness, is associated with hyperglycemia and/or DM in Brazilian subjects. In a cross-sectional design, 415 individuals of both sexes (46.7% male) were interviewed by a questionnaire and the DM diagnostic was self-reported. Anthropometric measurements, such as weight, height, body mass index (BMI), arm circumference, mid-arm and calf circumference and handgrip strength, were obtained by trained nutritionists. Blood glucose concentrations were determined by portable monitor analysis. Student's t-test was applied to compare DM cases with non-diabetic individuals, and logistic regression analysis was performed to verify the odds for becoming diabetic or having altered glycemia and p < 0.05 was considered as significant. From 415 subjects, 9.2% (n = 35) were classified as DM. DM patients had significantly higher age, BMI, casual glycemia and lower handgrip strength and normalized (to body weight) handgrip strength (NHS) when compared with non-diabetic patients. Individuals with low NHS have 2.7 odds ratio to DM without adjustment for covariate (crude model, p = 0.006) and have 2.7 times higher the likelihood of DM than individuals with high NHS after adjusting for age (model 1, p = 0.006); however, this association disappeared after further adjusting for sex. In conclusion, low handgrip strength normalized or not to body weight, was not associated with hyperglycemia and DM diagnosis.

Nuts and Human Health Outcomes: A Systematic Review.

There has been increasing interest in nuts and their outcome regarding human health. The consumption of nuts is frequently associated with reduction in risk factors for chronic diseases. Although nuts are high calorie foods, several studies have reported beneficial effects after nut consumption, due to fatty acid profiles, vegetable proteins, fibers, vitamins, minerals, carotenoids, and phytosterols with potential antioxidant action. However, the current findings about the benefits of nut consumption on human health have not yet been clearly discussed. This review highlights the effects of nut consumption on the context of human health.

Modulation of inflammatory response arising from high-intensity intermittent and concurrent strength training in physically active males.

The purposes of this study were to determine: (i) the extent of an acute session of high-intensity intermittent exercise (HIIE) followed by a concurrent strength session (Conc) on the increase of systemic inflammatory cytokines and chemokines, and (ii) whether eight weeks of high intensity interval training plus concurrent strength training alters the acute inflammatory response and immune status. Ten recreationally active males (aged 26.9±4.3years) performed two experimental exercise sessions interspersed by eight weeks of HIIT plus concurrent strength training. The experimental exercise session was composed of a 5-km run on a treadmill (1:1 at 100% of maximal aerobic speed (MAS)), and after 10min of passive recovery, back squat exercises were performed (80% 1RM, four sets until exhaustion). Serum samples were collected after fasting, pre-HIIE, post-HIIE, Pre-Conc, Post-Conc, and 30 and 60min post-exercise session. The comparison between both concurrent exercise sessions was performed using repeated measure ANOVA, with the Bonferroni Post-hoc when necessary. Interleukin-6 (IL-6) presented a moment effect (F=6.72; p<0.05), with Post-Conc significantly higher than pre-HIIE, Post-HIIE, and 60min, only a tendency was found between pre-HIIE and post-HIIE (difference=-5.99; p=0.09). MCP-1 and IL-1ra did not present effects for condition, moment, or interaction. Interleukin-10 (IL-10) presented both moment and interaction effects (F=5.31 and 2.50; p=0.005 and 0.036). Pre-Conc and Post-Conc were significantly higher than Pre-HIIE. The interaction between before and after eight weeks of concurrent training probably occurred at Post-Conc (11.42±3.09pgmL-1 and 8.88±1.29pgmL-1). In addition, maintenance of immune function was observed. Therefore, HIIE and concurrent strength exercise lead to an increase in cytokines response, but eight weeks of training program promoted anti-inflammatory response after an acute session of concurrent exercise.

Sarcopenia and chemotherapy-mediated toxicity / Sarcopenia e toxicidade mediada pela quimioterapia

ABSTRACT This narrative review focuses on the role of sarcopenia and chemotherapy-induced toxicity in cancer patients. Consistent evidence shows that sarcopenia in cancer patients leads to decreased overall survival by influencing treatment discontinuation and dose reduction. Therefore, sarcopenia should be considered a robust prognostic factor of negative outcome as well as a determinant of increased healthcare costs.

RESUMO Esta revisão narrativa descreve o papel da sarcopenia e a toxicidade mediada pela quimioterapia em pacientes com câncer. Diversas evidências consistentes mostram que a sarcopenia em pacientes com câncer induz à menor sobrevida global, por influenciar na interrupção do tratamento e na redução da dose. Portanto, a sarcopenia pode ser considerada um importante fator de prognóstico de desfecho negativo, além de um determinante de maiores custos em saúde.

Creatine supplementation and glycemic control: a systematic review.

The focus of this review is the effects of creatine supplementation with or without exercise on glucose metabolism. A comprehensive examination of the past 16 years of study within the field provided a distillation of key data. Both in animal and human studies, creatine supplementation together with exercise training demonstrated greater beneficial effects on glucose metabolism; creatine supplementation itself demonstrated positive results in only a few of the studies. In the animal studies, the effects of creatine supplementation on glucose metabolism were even more distinct, and caution is needed in extrapolating these data to different species, especially to humans. Regarding human studies, considering the samples characteristics, the findings cannot be extrapolated to patients who have poorer glycemic control, are older, are on a different pharmacological treatment (e.g., exogenous insulin therapy) or are physically inactive. Thus, creatine supplementation is a possible nutritional therapy adjuvant with hypoglycemic effects, particularly when used in conjunction with exercise.

Doxorubicin caused severe hyperglycaemia and insulin resistance, mediated by inhibition in AMPk signalling in skeletal muscle.

BACKGROUND: Cancer is considered the second leading cause of death in the world, and for the treatment of this disease, pharmacological intervention strategies are frequently based on chemotherapy. Doxorubicin (DOX) is one of the most widely used chemotherapeutic agents in clinical practice for treating a number of solid tumours. The treatment with DOX mimics some effects of cancer cachexia, such as anorexia, asthenia, decreases in fat and skeletal muscle mass and fatigue. We observed that treatment with DOX increased the systemic insulin resistance and caused a massive increase in glucose levels in serum. Skeletal muscle is a major tissue responsible for glucose uptake, and the positive role of AMPk protein (AMP-activated protein kinase) in GLUT-4 (Glucose Transporter type 4) translocation, is well established. With this, our aim was to assess the insulin sensitivity after treatment with DOX and involvement of AMPk signalling in skeletal muscle in this process. METHODS: We used Wistar rats which received a single dose of doxorubicin (DOX group) or saline (CT group) intraperitoneally at a dose of 15 mg/kg b.w. The expression of proteins involved in insulin sensitivity, glucose uptake, inflammation, and activity of electron transport chain was assessed in extensor digitorum longus muscle, as well as the histological evaluation. In vitro assays were performed in L6 myocytes to assess glucose uptake after treatment with DOX. Agonist of AMPk [5-aminoimidazole-4-carboxamide (AICAR)] and the antioxidant n-acetyl cysteine were used in L6 cells to evaluate its effect on glucose uptake and cell viability. RESULTS: The animals showed a significant insulin resistance, hyperglycaemia, and hyperinsulinemia. A decrease in the expression of AMKP and GLUT-4 was observed in the extensor digitorum longus muscle. Also in L6 cells, DOX leads to a decrease in glucose uptake, which is reversed with AICAR. CONCLUSIONS: DOX leads to conditions similar to cachexia, with severe glucose intolerance both in vivo and in vitro. The decrease of AMPk activity of the protein is modulated negatively with DOX, and treatment with agonist of AMPk (AICAR) has proved to be a possible therapeutic target, which is able to recover glucose sensitivity in skeletal muscle.

Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.

White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects.