Doxorubicin causes cachexia, sarcopenia, and frailty characteristics in mice.

While chemotherapy treatment can be lifesaving, it also has adverse effects that negatively impact the quality of life. To investigate the effects of doxorubicin chemotherapy on body weight loss, strength and muscle mass loss, and physical function impairments, all key markers of cachexia, sarcopenia, and frailty. Seventeen C57/BL/6 mice were allocated into groups. 1) Control (n = 7): mice were exposed to intraperitoneal (i.p.) injections of saline solution. 2) Dox (n = 10): mice were exposed to doxorubicin chemotherapy cycles (total dose of 18 mg/kg divided over 15 days). The body weight loss and decreased food intake were monitored to assess cachexia. To assess sarcopenia, we measured muscle strength loss using a traction method and evaluated muscle atrophy through histology of the gastrocnemius muscle. To evaluate physical function impairments and assess frailty, we employed the open field test to measure exploratory capacity. Doxorubicin administration led to the development of cachexia, as evidenced by a significant body weight loss (13%) and a substantial decrease in food intake (34%) over a 15-day period. Furthermore, 90% of the mice treated with doxorubicin exhibited sarcopenia, characterized by a 20% reduction in traction strength (p<0,05), a 10% decrease in muscle mass, and a 33% reduction in locomotor activity. Importantly, all mice subjected to doxorubicin treatment were considered frail based on the evaluation of their overall condition and functional impairments. The proposed model holds significant characteristics of human chemotherapy treatment and can be useful to understand the intricate relationship between chemotherapy, cachexia, sarcopenia, and frailty.

Pre and Post-high-intensity Interval Training Delays Colon Tumor Onset in a Syngeneic Mouse Model.

BACKGROUND/AIM: High-intensity interval training (HIIT) can trigger transient anti-tumor cytotoxicity through the mobilization of natural killer cells (NK cells) and myokines. Yet, the effects of HIIT on tumor development and microenvironment are unclear. MATERIALS AND METHODS: Male C57/BL6 mice were administered either MC38 of syngeneic colon cancer cells or vehicle in a single subcutaneous injection. Before injection, the training group completed four weeks of the HIIT program (progressive swimming training, 3/week, 10-12 min, 4-6% of body weight for overload). Following injection, trained mice continued to exercise for two additional weeks. RESULTS: Pre and post-HIIT training was effective in preventing tumor onset (p=0.0065), maintaining body weight gain, and counteracting splenomegaly by 40% compared to the tumor group. However, HIIT had no impact on suppressing tumor growth, modifying final tumor volume, or significantly changing tumor proliferation (Ki-67), connective tissue content, or DNA double-strand damage detected by phospho-histone gamma-H2AX (γ-H2AX). CONCLUSION: Pre and post-HIIT program is feasible for mice carrying a subcutaneous syngeneic tumor and effective in delaying tumor burden; however, HIIT did not alter colon tumor endpoints.

Chemotherapy periodization to maximize resistance training adaptations in oncology.

INTRODUCTION: Engaging in exercise programs during cancer treatment is challenging due to the several chemotherapy-induced side effects. Using a pre-clinical model that mimics chemotherapy treatment, we investigated if a periodized-within-chemotherapy training strategy can maximize resistance training (RT) adaptations such as increasing muscle mass and strength. METHODS: Swiss mice were randomly allocated into one of the following five groups (n = 14): control (C), resistance training (RT), chemotherapy-treated non-exercised group (Ch), resistance training chemotherapy treated (RTCh), and resistance training periodized-within-chemotherapy (RTPCh). Doxorubicin (i.p.) was weekly injected for a total of 3 weeks (total dose of 12 mg/kg). Resistance training consisted of ladder climbing with progressive intensity, three times a week for 3 weeks, during chemotherapy treatment. RTPCh prescriptions considered "bad day" adjustments while RTCh did not. "Bad day" adjustments considered the presence or absence of clinical signs (e.g., severe weight loss, diarrhea, mice refusing to train) to replace RT sessions. At the end of the third week, animals were euthanized. RESULTS: Weekly doxorubicin injection promoted progressive body weight loss, muscle atrophy, strength loss, local oxidative stress, and elevated inflammatory mediators, such as TNF-α and IL-6. Non-periodized-within-chemotherapy RT promoted mild protection against doxorubicin-induced skeletal muscle disturbances; moreover, when periodized-within-chemotherapy was applied, RT prevented elevated skeletal muscle inflammatory mediators and oxidative damage markers and promoted muscle mass and strength gains. CONCLUSION: Considering chemotherapy-induced side effects is a crucial aspect when prescribing resistance exercise during cancer, it will maximize the effectiveness of exercise in enhancing muscle mass and strength.

Effects of lipodystrophy and physical exercise on bioimpedance parameters in people living with HIV: A cross-sectional study.

OBJECTIVE: The aim of this study was to evaluate the effects of lipodystrophy and physical exercise on the parameters of bioimpedance spectroscopy (BIS) and bioimpedance vector analysis (BIVA) of people living with HIV (PLWHIV). METHODS: Seventy patients were divided into two groups: PLWHIV with lipodystrophy (PLWHIV-L) and PLWHIV without lipodystrophy (PLWHIV-NL). The phase angle (PhA) and the BIVA were determined from the values of resistance and reactance collected by the BIS. The percentage of fat mass and lean soft tissue (LST) were determined by dual-energy x-ray absorptiometry. For comparisons between the PLWHIV-L and PLWHIV-NL groups, the t test for independent samples or the Mann-Whitney test was used. From the BIVA, the average of the impedance vectors of the two groups was calculated with the 95% confidence ellipse, and the individual vectors of the patients divided by sex were also compared with the tolerance ellipses of 50%, 75%, and 95% of the healthy reference population. The relationships between the variables of interest were determined by the Pearson or Spearman correlation coefficient and the coefficient of determination. Analysis of covariance was used for comparisons between groups, adjusted for possible confounding variables. RESULTS: PLWIV-L showed better hydration conditions (P <0.01), higher LST (P <0.01), and lower percent of fat mass (P <0.01). No differences in PhA were observed between PLWHIV who practiced or did not practice physical exercise. There was a significant difference between the impedance vectors of the groups with and without lipodystrophy (T = 42.4 and P <0.01). Additionally, most of the patients who were positioned beyond the ellipse limits of 50% of tolerance fell into the areas of edema and cachexia. The extracellular to intracellular water ratio explained 81% of the PhA variations. When PhA was adjusted for height2, fat mass/height2 and LST, it was significantly different between groups of the female sex (PhA: P <0.01). CONCLUSION: Lipodystrophy and the practice of physical exercise do not present direct involvement in the PhA values, with sex, body composition, and hydration variables being the main influences on this variable. BIVA was able to show differences in the body composition of the groups even when the PhA values were similar.

Creatine Supplementation Potentiates Exercise Protective Effects against Doxorubicin-Induced Hepatotoxicity in Mice.

We tested the hypothesis that creatine supplementation may potentiate exercise's protective effects against doxorubicin-induced hepatotoxicity. Thirty-eight Swiss mice were randomly allocated into five groups: control (C, n = 7), exercised (Ex, n = 7), treated with doxorubicin (Dox, n = 8), treated with doxorubicin and exercised (DoxEx, n = 8), and treated with doxorubicin, exercised, and supplemented with creatine (DoxExCr, n = 8). Doxorubicin was administered weekly (i.p.) for a total dose of 12 mg/kg. Creatine supplementation (2% added to the diet) and strength training (climbing stairs, 3 times a week) were performed for a total of 5 weeks. The results demonstrated that doxorubicin caused hepatotoxicity, which was evidenced by increased (p < 0.05) hepatic markers of inflammation (i.e., TNF-α and IL-6) and oxidative damage, while the redox status (GSH/GSSG) was reduced. The plasma concentrations of liver transaminases were also significantly (p < 0.05) elevated. Furthermore, doxorubicin-treated animals presented hepatic fibrosis and histopathological alterations such as cellular degeneration and the infiltration of interstitial inflammatory cells. Exercise alone partly prevented doxorubicin-induced hepatotoxicity; thus, when combined with creatine supplementation, exercise was able to attenuate inflammation and oxidative stress, morphological alterations, and fibrosis. In conclusion, creatine supplementation potentiates the protective effects of exercise against doxorubicin-induced hepatotoxicity in mice.

Effect of Resistance Exercise Order on Cardiovascular Disease Risk Factors in Older Women: A Randomized Controlled Trial.

We compared the effects of two specific resistance training (RT) exercise orders on cardiovascular risk factors. Forty-four untrained older women (>60 years) were randomly assigned to three groups: control (CON, n = 15), multi-joint to single-joint (MJ-SJ, n = 14), and single-joint to multi-joint (SJ-MJ, n = 15) exercise orders. Training groups performed a whole-body RT program (eight exercises, 3 × 10−15 repetitions for each exercise) over 12 weeks in 3 days/week. Body fat, triglycerides, total cholesterol, HDL-c, LDL-c, VLDL-c, glucose, IL-6, IL-10, TNF-α, C-reactive protein, total radical-trapping antioxidant (TRAP), advanced oxidation protein products (AOPP), ferrous oxidation-xylenol (FOX), and nitric oxide concentrations (NOx) were determined pre- and post-intervention. Significant interaction group × time (p < 0.05) revealed reducing fat mass and trunk fat and improvements in glucose, LDL-c, IL-10, TNF-α, C-reactive protein, FOX, and AOPP concentrations in both training groups, without differences between them (p > 0.05). The results suggest that 12 weeks of RT, regardless of exercise order, elicit positive adaptations on body fat and metabolic biomarkers similarly in older women.

The interplay between physiotherapist and exercise physiologist in the exercise oncology program / A interação entre fisioterapeuta e o profissional de educação física no programa de exercício oncológico

ABSTRACT Exercise is a relevant tool in the oncology rehabilitation program due to restoring functional capacity, improving quality of life, and preventing early cancer mortality, mainly in unfit cancer patients. According to a systematic physical evaluation and risk stratification model, exercise physiologists (or equivalent) and physiotherapists with additional cancer exercise training are candidates to provide and supervise exercise to cancer survivors. However, the referral pathways are unclear, and a few cancer survivors are educated about personalized exercise oncology programs. This article aims to engage and stimulate additional training of Exercise physiologists and Physiotherapists in a collaborative exercise oncology program and proposes a dynamic and supervised model to attend to the emerging multidisciplinary scenario of cancer.

RESUMO Exercício físico é uma ferramenta fundamental no programa de reabilitação oncológica. Seu foco está em restaurar parâmetros físico-funcionais, melhorar a qualidade de vida e prevenir mortalidade precoce, especialmente em pacientes oncológicos mais fragilizados. Profissionais de educação física e fisioterapeutas com capacitação em oncologia são elegíveis em prescrever e supervisionar exercícios a esse público, seguindo um criterioso modelo de avaliação contínua e estratificação de risco. Contudo, o fluxo de direcionamento do paciente oncológico a esses profissionais não está estabelecido e poucos pacientes são beneficiados por um programa de exercícios personalizados no Brasil. Este artigo tem o objetivo de engajar e estimular a capacitação de profissionais de educação física e fisioterapeutas no programa de exercício oncológico e propor um modelo colaborativo de avaliação e supervisão de exercícios alinhado a um crescente cenário multidisciplinar do câncer.

Effect of a single resistance exercise session on inflammatory markers and oxidative stress in women living with HIV / Efeito de uma única sessão de exercício resistido sobre marcadores inflamatórios e estresse oxidativo em mulheres vivendo com hiv

ABSTRACT People living with HIV (PLH), who use antiretroviral therapy (ART), are more susceptible to changes in the inflammatory profile and oxidative stress, and women have greater access to ART. Although physical exercise is a complementary strategy to treatment due to its antioxidant and anti-inflammatory effects, it is not clear whether acute responses to exercise can be harmful to PLH. The aim of the study was to investigate the acute effect of resistance exercise (RE) on inflammatory and oxidative stress markers in PLH. Ten women, using ART, performed RE session consisting of seven exercises for the whole body. For biochemical evaluation, blood samples were collected before (pre), 1 hour (1h) and 2 hours (2h) after the RE session. One-way ANOVA followed by Bonferroni's post hoc test was used to compare results between time points. There was an increase only in markers, GSSG of 160% (pre: 0.40 ± 0.11; 1h: 1.18 ± 0.36; 2h: 1.04 ± 0.25 mmol/g), TNF-α of 98 % (pre: 4.60 ± 0.55; 1h: 6.95 ± 0.77; 2h: 9.10 ± 1.03 pg/ml) and 52% IL-6 (pre: 2.47 ± 0 .67; 1h: 3.63 ± 1.26; 2h: 5.38 ± 2.15 pg/ml). The other variables remained unchanged (P > 0.05). It is concluded that a RE session increased the levels of inflammatory markers and oxidative stress in PLH in a non-exacerbated way.

RESUMO Pessoas vivendo com HIV (PVH), que utilizam a terapia antirretroviral (TARV), são mais suscetíveis a alterações no perfil inflamatório e estresse oxidativo, sendo que as mulheres possuem maior acesso à TARV. Embora o exercício físico seja uma estratégia complementar ao tratamento devido aos seus efeitos antioxidantes e anti-inflamatórios, não está claro se as respostas agudas ao exercício podem ser prejudiciais às PVH. O objetivo do estudo foi investigar o efeito agudo de exercícios com pesos (EP) sobre marcadores inflamatórios e de estresse oxidativo em PVH. Dez mulheres, em uso da TARV, realizaram uma sessão de EP constituída por sete exercícios para o corpo todo. Para avaliação bioquímica, amostras de sangue foram coletadas antes (pré), 1 hora (1h) e 2 horas (2h) após a sessão de EP. A ANOVA one-way seguida do teste post hoc de Bonferroni foi utilizada para comparação dos resultados entre os momentos. Houve aumento apenas nos marcadores, GSSG de 160% (pré: 0,40 ± 0,11; 1h: 1,18 ± 0,36; 2h:1,04 ± 0,25 mmol/g), TNF-α de 98% (pré: 4,60 ± 0,55; 1h: 6,95 ± 0,77; 2h: 9,10 ± 1,03 pg/ml) e IL-6 de 52% (pré: 2,47 ± 0,67; 1h: 3,63 ± 1,26; 2h: 5,38 ± 2,15 pg/ml). As demais variáveis permaneceram sem alterações (P > 0,05). Conclui-se que uma sessão de EP aumentou os níveis de marcadores inflamatórios e estresse oxidativo em PVH de forma não exacerbada.

Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice.

Purpose: Although the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice. Methods: Male Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting. Results: Resistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia. Conclusion: Our results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

Sarcopenia Related to Human Immunodeficiency Virus: Protective Effects of Exercise.

We discuss recent evidence supporting the hypothesis that sarcopenia is an emerging health concern among people with human immunodeficiency virus (HIV) because of increasing life expectancy and HIV- and treatment-related comorbidities. We also hypothesize that combined exercise at higher intensity has a key role in managing sarcopenia in this population because it directly (increases muscle strength and stimulates hypertrophy) and indirectly (prevents mitochondrial dysfunction, oxidative stress, and persistent inflammation) counteracts sarcopenia hallmarks.

Physical activity recommendations for cancer prevention and control: a Brazilian consortium

Objective: This article describes the development process and summarizes the results of the Brazilian physical activity recommendations for cancer prevention and control, which was prepared to support health-care professionals. Material and Methods: These recommendations were elaborated considering: (i) the effect of physical activity on cancer prevention in the general healthy population; and (ii) on all-cause and cancer-specific mortality in cancer survivors. The process of preparing the recommendations was systematized, transparent and reproducible, following the recommendations of the appraisal of guidelines for research and evaluation (AGREE-II). We appraised the certainty of evidence for breast, prostate, colorectal and lung cancers, which are among the most frequent in Brazil, using the grading of recommendations, assessment, development and evaluations (GRADE) approach. Results: Regarding the risk of cancer, we found high certainty of evidence supporting the association between moderate-to-vigorous physical activity and lower risk of breast and colon cancer, moderate certainty of evidence for lung cancer and low certainty of evidence for prostate and rectal cancer. We found moderate certainty of evidence supporting the association between moderate-to-vigorous physical activity and reduction of all-cause and cancer-specific mortality from breast, colon and rectal cancer, and cancer-specific mortality from prostate cancer, when physical activity was performed after the disease diagnosis. We found low certainty of evidence for the association between physical activity and lung cancer mortality. Based on our findings, physical activity recommendations were proposed, including a step-by-step guide to support health-care professionals when recommending physical activity for all adults (including elderly people), with or without a diagnosis of cancer. Conclusion: Our recommentations may be useful to support health-care professionals counselling for physical activity, which contribute to reductions in physical inactivity in the general population and in the growing population of cancer survivors

Resistance Training's Ability to Prevent Cancer-induced Muscle Atrophy Extends Anabolic Stimulus.

PURPOSE: This study aimed to determine the role of mammalian target of rapamycin (mTORC1) activation and catabolic markers in resistance training's (RT) antiatrophy effect during cachexia-induced muscle loss. METHODS: Myofiber atrophy was induced by injecting Walker 256 tumor cells into rats exposed or not exposed to the RT protocol of ladder climbing. The role of RT-induced anabolic stimulation was investigated in tumor-bearing rats with the mTORC1 inhibitor rapamycin, and cross-sectional areas of skeletal muscle were evaluated to identify atrophy or hypertrophy. Components of the mTORC1 and ubiquitin-proteasome pathways were assessed by real-time polymerase chain reaction or immunoblotting. RESULTS: Although RT prevented myofiber atrophy and impaired the strength of tumor-bearing rats, in healthy rats, it promoted activated mTORC1, as demonstrated by p70S6K's increased phosphorylation and myofiber's enlarged cross-sectional area. However, RT promoted no changes in the ratio of p70S6K to phospho-p70S6K protein expression while prevented myofiber atrophy in tumor-bearing rats. Beyond that, treatment with rapamycin did not preclude RT's preventive effect on myofiber atrophy in tumor-bearing rats. Thus, RT's ability to prevent cancer-induced myofiber atrophy seems to be independent of mTORC1's and p70S6K's activation. Indeed, RT's preventive effect on cancer-induced myofiber atrophy was associated with its capacity to attenuate elevated tumor necrosis factor α and interleukin 6 as well as to prevent oxidative damage in muscles and an elevated abundance of atrogin-1. CONCLUSIONS: By inducing attenuated myofiber atrophy independent of mTORC1's signaling activation, RT prevents muscle atrophy during cancer by reducing inflammation, oxidative damage, and atrogin-1 expression.

Angiotensin 1-7 protects against ventilator-induced diaphragm dysfunction.

Mechanical ventilation (MV) is a life-saving instrument used to provide ventilatory support for critically ill patients and patients undergoing surgery. Unfortunately, an unintended consequence of prolonged MV is the development of inspiratory weakness due to both diaphragmatic atrophy and contractile dysfunction; this syndrome is labeled ventilator-induced diaphragm dysfunction (VIDD). VIDD is clinically important because diaphragmatic weakness is an important contributor to problems in weaning patients from MV. Investigations into the pathogenesis of VIDD reveal that oxidative stress is essential for the rapid development of VIDD as redox disturbances in diaphragm fibers promote accelerated proteolysis. Currently, no standard treatment exists to prevent VIDD and, therefore, developing a strategy to avert VIDD is vital. Guided by evidence indicating that activation of the classical axis of the renin-angiotensin system (RAS) in diaphragm fibers promotes oxidative stress and VIDD, we hypothesized that activation of the nonclassical RAS signaling pathway via angiotensin 1-7 (Ang1-7) will protect against VIDD. Using an established animal model of prolonged MV, our results disclose that infusion of Ang1-7 protects the diaphragm against MV-induced contractile dysfunction and fiber atrophy in both fast and slow muscle fibers. Further, Ang1-7 shielded diaphragm fibers against MV-induced mitochondrial damage, oxidative stress, and protease activation. Collectively, these results reveal that treatment with Ang1-7 protects against VIDD, in part, due to diminishing oxidative stress and protease activation. These important findings provide robust evidence that Ang1-7 has the therapeutic potential to protect against VIDD by preventing MV-induced contractile dysfunction and atrophy of both slow and fast muscle fibers.

Creatine supplementation does not promote tumor growth or enhance tumor aggressiveness in Walker-256 tumor-bearing rats.

OBJECTIVES: This study aimed to analyze the effect of creatine (Cr) supplementation on tumor microenvironment, evaluating the parameters of tumor aggressiveness. METHODS: Sixteen male Wistar rats were randomly assigned to 2 groups (n = 8/group): Tumor-bearing (T) and tumor-bearing supplemented with Cr (TCr). Cr supplementation was provided in drinking water for a total of 21 d. After 11 d of Cr supplementation (TCr group) or water (T group), Walker-256 tumor cells were inoculated subcutaneously in the right flank of all rats, which kept receiving Cr supplementation (TCr group) or water (T group) for 10 more days. The total period of the experiment was 21 d. RESULTS: Tumor weight corresponded with approximately 3.5% ± 0.9% of animal body weight in the T group. Cr supplementation did not accelerate tumor growth or increase tumor size. The histopathological analysis demonstrated the presence of nuclear pleomorphisms and atypical nuclei, with the presence of low-differentiated tumor cells, in both groups. Cr supplementation did not alter apoptosis and cell proliferation markers, nor tumor capsule thickness and viable tumor area. CONCLUSIONS: Cr supplementation in Walker-256 tumor-bearing rats did not induce significant changes in tumor development, and did not interfere with the parameters of tumor aggressiveness, such as the level of cell differentiation and proliferation.

Sarcopenia in people living with the Human Immunodeficiency Virus: a systematic review and meta-analysis.

People living with HIV (PLHIV) experience greater loss of muscle mass and function than people without HIV. However, HIV is not routinely recognized as a sarcopenia risk factor outside of HIV literature. The purposes of this study were to establish the prevalence and predictors of sarcopenia among PLHIV, and to compare the prevalence of sarcopenia among PLHIV and people without HIV. A systematic literature search of the PubMed, Embase, Cinahl, and Scielo databases was performed following PRISMA and MOOSE guidelines. Identified articles were included if they evaluated sarcopenia among PLHIV using either the presence of low muscle mass only or low muscle mass in association with low muscle function. The pooled prevalence of sarcopenia among PLHIV and the odds ratio for sarcopenia in PLHIV compared with controls were calculated. From 13 studies and 2267 participants, the prevalence of sarcopenia among PLHIV was 24.1% (95% CI = 17.8-31.0%). PLHIV presented 6.1 greater odds (95% CI = 1.1-33.5) of sarcopenia compared with people without HIV, matched by age, sex, BMI, and ethnicity. Longer exposure to specific HIV drugs, tobacco and alcohol, lower education and employment rates, and greater HIV duration were associated with sarcopenia. In conclusion, PLHIV had a high prevalence of sarcopenia, related to both HIV and non-HIV risk factors. HIV should be considered a risk factor for sarcopenia in the general population. CRD42019131449.

One-Carbon Metabolism in Fatty Liver Disease and Fibrosis: One-Carbon to Rule Them All.

Nonalcoholic fatty liver disease (NAFLD) is a term used to characterize a range of disease states that involve the accumulation of fat in the liver but are not associated with excessive alcohol consumption. NAFLD is a prevalent disease that can progress to organ damage like liver cirrhosis and hepatocellular carcinoma. Many animal models have demonstrated that one-carbon metabolism is strongly associated with NAFLD. Phosphatidylcholine is an important phospholipid that affects hepatic lipid homeostasis and de novo synthesis of this phospholipid is associated with NAFLD. However, one-carbon metabolism serves to support all cellular methylation reactions and catabolism of methionine, serine, glycine, choline, betaine, tryptophan, and histidine. Several different pathways within one-carbon metabolism that play important roles in regulating energy metabolism and immune function have received less attention in the study of fatty liver disease and fibrosis. This review examines what we have learned about hepatic lipid metabolism and liver damage from the study of one-carbon metabolism thus far and highlights unexplored opportunities for future research.

Creatine supplementation in Walker-256 tumor-bearing rats prevents skeletal muscle atrophy by attenuating systemic inflammation and protein degradation signaling.

PURPOSE: The aim of this study was to investigate the effects of creatine supplementation on muscle wasting in Walker-256 tumor-bearing rats. METHODS: Wistar rats were randomly assigned into three groups (n = 10/group): control (C), tumor bearing (T), and tumor bearing supplemented with creatine (TCr). Creatine was provided in drinking water for a total of 21 days. After 11 days of supplementation, tumor cells were implanted subcutaneously into T and TCr groups. The animals' weight, food and water intake were evaluated along the experimental protocol. After 10 days of tumor implantation (21 total), animals were euthanized for inflammatory state and skeletal muscle cross-sectional area measurements. Skeletal muscle components of ubiquitin-proteasome pathways were also evaluated using real-time PCR and immunoblotting. RESULTS: The results showed that creatine supplementation protected tumor-bearing rats against body weight loss and skeletal muscle atrophy. Creatine intake promoted lower levels of plasma TNF-α and IL-6 and smaller spleen morphology changes such as reduced size of white pulp and lymphoid follicle compared to tumor-bearing rats. In addition, creatine prevented increased levels of skeletal muscle Atrogin-1 and MuRF-1, key regulators of muscle atrophy. CONCLUSION: Creatine supplementation prevents skeletal muscle atrophy by attenuating tumor-induced pro-inflammatory environment, a condition that minimizes Atrogin-1 and MuRF-1-dependent proteolysis.

Effects of pre- or post-exercise whey protein supplementation on oxidative stress and antioxidant enzymes in older women.

BACKGROUND: Oxidative stress is an imbalance between antioxidant system and production of free radicals and has been associated with the age-related deleterious changes. The defense system can be modulated by exercise and nutrition. OBJECTIVE: The purpose of this investigation was to evaluate the effect of whey protein supplementation pre- or post-resistance training on oxidative stress and antioxidant enzyme activity in pre-conditioned older women. METHODS: In a randomized, double-blind, and placebo-controlled design, 70 older women (≥60 years) were randomly assigned to one of the following three groups: whey protein-placebo (WP-PLA, n = 24), placebo-whey protein (PLA-WP, n = 23), and placebo-placebo (PLA-PLA, n = 23). Each group received 35 g of whey product or placebo pre- and post-training. The RT program was carried out over 12 weeks (3x/week; 3x 8-12 repetitions maximal). Oxidative stress and blood markers were assessed before and after intervention period. ANOVA for repeated measures was used for data analysis. RESULTS: There was a significant time effect (P < 0.05), with all groups showing improvements in all oxidative stress markers and antioxidant enzyme activity. A significant (P < 0.001) interaction time vs group was observed for uric acid, with both WP-PLA and PLA-WP presenting greater reductions compared with the PLA-PLA, without differences between the timing of protein intake (WP-PLA: -8.3%; PLA-WP: -11.0%; PLA-PLA:-2.0%). CONCLUSION: In already pre-conditioned older women, whey protein supplementation reduces plasma uric acid concentration with no further effect on antioxidant enzyme activity and oxidative stress markers. ClinicalTrials.gov: NCT03247192.

Resistance Exercise Counteracts Tumor Growth in Two Carcinoma Rodent Models.

PURPOSE: Although resistance exercise (RE) is now recognized as an adjuvant in cancer treatment because of its capacity to prevent muscle wasting, weakness, and cachexia, it is unknown whether RE can mitigate tumor development. Two solid adenocarcinoma models (Walker-256 and Ehrlich) were used to investigate the effects of RE on tumor cell proliferation, growth, and aggressiveness parameters in tumor-bearing animals' life span. METHODS: Walker-256 tumor-bearing rats and Ehrlich tumor-bearing mice were subjected to RE, which consisted of climbing a ladder apparatus with loads tied to their tails. After 4 wk, animals were euthanized, and tumors were excised and assessed for tumor microenvironment evaluation such as cell proliferation and apoptosis determination, collagen deposit, and presence of malignant tumor morphology. RESULTS: Our data demonstrate that RE mitigated tumor growth and favored tumor end points such as lower Scarff-Bloom-Richardson histological grade tumor, denoting slow cell aberrant form and division, decreased tumor cell proliferation (evaluated by nucleus marked with antigen ki-67), and lower viable tumor area in both types of tumors studied. In addition, RE stimulated tumor microvessel density in Walker-256 tumor-bearing rats, but there was no change in their life span. CONCLUSION: RE may mitigate tumor growth and tumor malignancy parameters such as lower histopathological grade, assuming less nuclear pleomorphism and mitotic cells, smaller viable tumor area, and decreased tumor cell proliferation in both adenocarcinomas. In addition, RE induced tumor vascularization.

Antioxidant vitamin supplementation prevents oxidative stress but does not enhance performance in young football athletes.

OBJECTIVES: The aim of this study was to verify the effects of supplementation with antioxidants (vitamins C and E) on oxidative stress, delayed-onset muscle soreness (DOMS), and performance in football players during a recovery period after an exercise-induced oxidative stress protocol. METHODS: Twenty-one football athletes were randomly assigned to two groups: placebo and antioxidant-supplemented. Supplementation was performed in a double-blind, controlled manner using vitamin C (500 mg/d) and E (400 UI/d) for 15 d. After 7 d of supplementation, athletes were submitted to an exercise-induced oxidative stress protocol consisting of plyometric jumping and strength resistance sets to exhaustion. Blood samples, performance tests, and DOMS were determined before and 24, 48, and 72 h after exercise. RESULTS: Antioxidant supplementation was continued during the recuperation week and for a total of 15 d. Antioxidant supplementation caused a significant increase in plasma vitamins C and E. The antioxidant supplementation could inhibit oxidative stress characterized by elevated lipid peroxidation markers malondialdehyde and total lipid peroxidation as well as reduced ratio of glutathione to oxidized glutathione promoted by exercise. Antioxidant supplementation, however, did not significantly reduce the plasma creatine kinesis concentration or DOMS during the recovery days. Likewise, supplementation with vitamin C and E did not improve lower body power, agility, or anaerobic power, nor did it provide any indication of faster muscle recovery. CONCLUSION: Antioxidant supplementation does not attenuate elevated markers of muscle damage or muscle soreness promoted by acute exercise and do not exert any ergogenic effect on football performance of young athletes, although it reduced oxidative stress.