Artigos Científicos

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Obesity-like metabolic effects of high-carbohydrate or high-fat diets consumption in metabolic and renal functions.

Present study investigated which diet, high-carbohydrate (HCD) or high-fat (HFD), most effectively induces classical characteristics of obesity in mice. Mice were fed commercial chow (control), an HCD, or an HFD for 12 weeks. HFD and HCD increased body weight, fat mass, and glycaemia, whereas the HFD augmented insulinemia. In the kidney, the HFD caused albuminuria, and reductions in fractional Na+ excretion, Thromboxane B2 (TXB2) excretion, and urinary flow, whereas the HCD reduced glomerular filtration, plasma osmolality, and TXB2 and Prostaglandin E2 excretion. The consumption of HFD and HCD modified parameters that indicate histopathological changes, such as proliferation (proliferating-cell-nuclear antigen), inflammation (c-Jun N-terminal-protein), and epithelial-mesenchymal transition (vimentin, and desmin) in renal tissue, but the HCD group presents fewer signals of glomerular hypertrophy or tubule degeneration. In summary, the HCD generated the metabolic and renal changes required for an obesity model, but with a delay in the development of these modifications concerning the HFD.

Arch Physiol Biochem. 2021 Jan 27;1-11. doi: 10.1080/13813455.2021.1874019

Sapiens: Uma Revisão Sobre a Perspectiva da Neurociência Evolutiva.

Neste trabalho, apresentamos uma revisão crítica do livro: Sapiens: Uma Breve História da Humanidade, de Yuval Noah Harari, versão traduzida para o português, publicada em Porto Alegre, Brasil, em 20176. Embora o livro traga contribuições para diversas áreas da ciência, nossa abordagem pretende avaliar apenas as ideias relacionadas ao campo da neurociência evolutiva em geral, principalmente em relação às origens comportamentais, aspectos sociais e emocionais de nossa espécie tratadas pelo autor. Assim, entendemos que este livro traz importantes aspectos sobre os temas propostos, cumprindo uma dupla função, primeiro, atuando como instrumento de disseminação da ciência ao público leigo; segundo, trazendo à discussão importantes reflexões sobre neurociência evolutiva, para a comunidade acadêmica e científica.

Revista Neurociências, 28, 1–10. https://doi.org/10.34024/rnc.2020.v28.9924

Anthropometric Parameters in Celiac Disease: A Review on the Different Evaluation Methods and Disease Effects.

This review compiled anthropometric data from 29 original articles, published between 1995 and 2015, corresponding to a total sample of 6368 celiac disease subjects. Body mass index was the main parameter for measuring anthropometry (82.1%), followed by body mass (78.6%), body fat (51.7%), bone mineral density and bone mineral content (46.4%), and fat-free mass (44.8%). The main evaluation method was dual x-ray absorptiometry (83.3%), followed by bioimpedance (16.6%), skinfold thickness (16.6%), and isotope dilution (5.5%). This compilation suggests that celiac disease patients without a gluten-free diet (WGFD) and celiac disease patients with a gluten-free diet (GFD) show a lower body mass than the control group, with inconclusive data about WGFD versus GFD. Body mass index is lower in WGFD and GFD compared to control group, and is lower in WGFD compared to GFD. We observed lower values of FM and FFM in WGFD and GFD versus the control group. No difference was found between WGFD versus GFD. BMD and BMC are lower in WGFD versus GFD and GFD versus the control group, with inconclusive data about WGFD versus GFD. The findings of this review suggest that celiac disease patients must be periodically evaluated through anthropometric parameters, since the pathology has the potential to modulate such values even in a gluten-free diet, with these variables reflecting their healthy status. In parallel, the screening of different anthropometric assessment methodologies can provide support for more accurate evaluations by scientists and clinical professionals who work with celiac disease patients.

Journal of Nutrition and Metabolism Volume 2019, Article ID 4586963, https://doi.org/10.1155/2019/4586963

Does oil rich in alpha-linolenic fatty acid causes the same immune modulation than fish oil in Walker 256 tumor-bearing rats?

Objetive:Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid.

Methods: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated.

Results: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8+) subpopulation, and increased TNF-α production.

Conclusions: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.

Nutr Cancer. Nov-Dec 2016;68(8):1369-1380. doi: 10.1080/01635581.2016.1224364

Chronic fish oil supplementation partially reverses renal alterations in mice fed with a high-fat diet.

The objective of this study was to investigate the alterations in renal morphology and function in an animal model of obesity, and to determine the possible effect of fish oil (FO) supplementation on these alterations. Six-week-old male mice were fed during eight weeks with regular rodent chow (R) or a high-fat diet (HFD), 53.09% fat. After this, they were supplemented orally for 30 days with FO. The weight gain of HFD group was almost three times higher than R. Albuminuria induced by HFD was significantly reduced by FO. The reduction in fractional sodium excretion (FENa+) observed in HFD group was reversed by FO. The HFD was able to increase in almost 100% the concentration of TNF-α in renal tissue, an effect reversed by FO. Intrarenal expression of vimentin was significantly higher in tubulointerstitial cells of HFD group, an effect reversed by FO. In summary, FO partially reverses renal alterations induced by an HFD.

Journal of Functional Foods 26:196-207 DOI:10.1016/j.jff.2016.07.016

α-Linolenic Fatty Acid Supplementation Decreases Tumor Growth and Cachexia Parameters in Walker 256 Tumor-Bearing Rats.

Fish oil (FO) has been shown to affect cancer cachexia, tumor mass, and immunity cell. n-3 PUFA, specifically α-linolenic fatty acid (ALA), has controversial effects. We investigated this in nontumor-bearing Wistar rats fed regular chow (C), fed regular chow and supplemented with FO or Oro Inca oil (OI), and Walker 256 tumor-bearing rats fed regular chow (W), fed regular chow and supplemented with FO (WFO) or OI (WOI). Rats were supplemented (1g/kg body weight/day) during 4 wk and then the groups tumor-bearing were inoculated with Walker 256 tumor cells suspension and 14 days later the animals were killed. WFO increased EPA fivefold and DHA 1.5-fold in the tumor tissue compared to W (P < 0.05). OI supplementation increased of threefold of ALA when compared to W (P < 0.05). Tumor mass in WFO and OI was of 2.3-fold lower, as well as tumor cell proliferation of 3.0-fold tumor tissue lipoperoxidation increased of 76.6% and cox-2 expression was 20% lower. Cachexia parameters were attenuate, blood glucose (25% higher), Triacylglycerolemia (50% lower), and plasma TNF-α (65% lower; P < 0.05) and IL-6 (62.5% lower). OI, rich in ALA, caused the same effect on cancer as those seen in FO.

Nutr Cancer. 2015;67(5):839-46. doi: 10.1080/01635581.2015.1043021. Epub 2015 May 26

Fish oil administration mediates apoptosis of Walker 256 tumor cells by modulation of p53, Bcl-2, caspase-7 and caspase-3 protein expression.

Background: Several studies have been shown pro-apoptotic effects of fish oil (FO), rich in n-3 polyunsaturated fatty acids (n-3 PUFA) on cancer cells. Nevertheless, few in vivo experiments have provided data of its ability on apoptosis protein expression in tumor tissue. Thus, in this study we investigate the effect of FO supplementation on apoptosis protein expression in Walker 256 tumor bearing rats. Male Wistar rats were randomly assigned to three groups: fed with regular chow (W); fed regular chow supplemented with FO (WFO) or coconut fat (WCO) (1 g/kg body weight/daily). After thirty days, all animals were inoculated subcutaneously with Walker 256 tumor cells.

Findings: Protein expression was done by western blotting in Walker 256 tumor tissue samples. FO decreased the Bcl-2/Bax ratio (p < 0.05) and increased the p53 (p < 0.05), cleaved caspase-7 (p < 0.05) and cleaved caspase-3 (p < 0.05) in Walker 256 tumor tissue.

Conclusions: Our data suggest that the pro-apoptotic effect of FO in Walker 256 tumor is related with specifics cleaved caspases.

Lipids Health Dis. 2015 Aug 25;14:94. doi: 10.1186/s12944-015-0098-y

Exercise and Shark Liver Oil Supplementation Reduce Tumor Growth and Cancer Cachexia in Walker 256 Tumor Bearing Rats.

This study investigated whether exercise associated to shark liver oil supplementation (1 g/kg b.w./day) affects tumor growth, cachexia, lipid peroxidation and proteins expression involved in cell death in Walker 256 tumorbearing rats. Animals were divided into 4 groups: sedentary tumor-bearing (W), sedentary tumor-bearing shark liver oil supplemented (WSL), exercised tumor-bearing (EW) and exercised tumor-bearing shark liver oil supplemented (EWSL). Training sessions consisted of 6 bouts, 30 seconds each with 50% body-weight load attached to the trunk followed by 1 minute of resting (jump training). Five minutes after the finish jump training the exercise groups were subjected to 30 minutes of continuous swimming with a load equivalent to 6% of body weight, 4 times a week during 8 weeks. Tumor cells were injected at the 6th training week and all groups were killed 15 days post inoculation. Tumor weight (g) in W group was of 26.50 ± 1.79 and in the WSL, EW and EWSL was of 14.08 ± 0.91, 15.60 ± 0.55 and 12.60 ± 1.07, respectively. The group W showed hypoglycemia (68.67 ± 2.12 mg/dl), hyperlactacidemia (1.49 ± 0.06 mmol/L), hypertriacylglycerolemia (161.4 ± 9.4 mg/dl) and body weight reduction (13.21 ± 2.25 g) characterizing cachexia state. The groups WSL, EW and EWSL presented reduction of tumor cells proliferation ex vivo, and the production of hydroperoxide and apoptosis was increased. Bax/Bcl-2 expression ratio was increased only in the exercised groups. Shark liver oil supplementation and exercise alone were able in to avoid the installation of cachexia state and also reduced tumor growth, but the association of both cause further effect only in the tumor growth.

J Cancer Sci Ther 2014, 6.3 doi: 10.4172/1948-5956.1000254

Antitumor and anti-cachectic effects of shark liver oil and fish oil: comparison between independent or associative chronic supplementation in Walker 256 tumor-bearing rats.

Background

Shark liver oil (SLOil) and fish oil (FOil), which are respectively rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), are able to reduce the growth of some tumors and the burden of cachexia. It is known that FOil is able to reduce proliferation rate and increase apoptotic cells and lipid peroxidation of tumor cells efficiently. However, there are few reports revealing the influence of SLOil on these parameters. In the current study, effects of FOil chronic supplementation on tumor growth and cachexia were taken as reference to compare the results obtained with SLOil supplementation. Also, we evaluated if the association of SLOil and FOil was able to promote additive effects.

Methods

Weanling male Wistar rats were divided into 4 groups: fed regular chow (C), supplemented (1 g/kg body weight) with SLOil (CSLO), FOil (CFO) and both (CSLO + FO). After 8 weeks half of each group was inoculated with Walker 256 cells originating new groups (W, WSLO, WFO and WSLO + FO). Biochemical parameters of cachexia, tumor weight, hydroperoxide content, proliferation rate and percentage of apoptotic tumor cells were analysed. Fatty acids and AKG composition of tumor and oils were obtained by high performance liquid chromatography and gas chromatography – mass spectrometry, respectively. Statistical analysis was performed by unpaired t-test and one-way ANOVA followed by a post hoc Tukey test.

Results

Fourteen days after inoculation, SLOil was able to restore cachexia parameters to control levels, similarly to FOil. WSLO rats presented significantly lower tumor weight (40%), greater tumor cell apoptosis (~3-fold), decreased tumor cell proliferation (35%), and higher tumor content of lipid hydroperoxides (40%) than observed in W rats, but FOil showed more potent effects. Supplementation with SLOil + FOil did not promote additive effects. Additionally, chromatographic results suggested a potential incorporation competition between the n-3 fatty acids and the AKGs in the tumor cells’ membranes.

Conclusions

SLOil is another marine source of lipids with similar FOil anti-cachectic capacity. Furthermore, despite being less potent than FOil, SLOil presented significant in vivo antitumor effects. These results suggest that the chronic supplementation with SLOil may be adjuvant of the anti-cancer therapy.

Lipids Health Dis. 2013; 12: 146.  doi: 10.1186/1476-511X-12-146

Effect of interval training on blood biochemical and immunological parameters in hypoinsulinemic streptozotocin-induced diabetic Wistar rats. 

Objective:

This study investigated the effect of interval training on blood biochemistry and immune parameters in type 1 diabetic rats.

Materials and methods:

Male Wistar rats were divided into four groups: sedentary (SE, n = 15), interval training (IT, n = 17), diabetic sedentary (DSE, n = 17), diabetic interval training (DIT, n = 17). Diabetes was induced by i.v. injection of streptozotocin (60 mg/kg). Swimming Interval Training consisted of 30-s exercise with 30-s rest, for 30 minutes, during 6 weeks, four times a week, with an overload of 15% of body mass. Plasma glucose, lactate, triacylglycerol and total cholesterol concentrations, phagocytic capacity, cationic vesicle content, and superoxide anion and hydrogen peroxide production by blood neutrophils and peritoneal macrophages were evaluated. Proliferation of mesenteric lymphocytes was also estimated.

Results:

Diabetes caused dyslipidemia and body weight loss. Interval training resulted in attenuation of the resting hyperglycemic state, reversed triacylglycerolemia and cholesterolemia in the DIT group. Diabetes increased the functionality of blood neutrophils and peritoneal macrophages in the DSE group. Interval training increased the phagocytic capacity, cationic vesicle content, superoxide anion production, and hydrogen peroxide production of peritoneal macrophages in the IT group. Interval training also led to a twofold increase in the proliferation of mesenteric lymphocytes after 6 weeks of exercise in the DIT group.

Conclusion:

Our ndings show that low-volume high-intensity physical exercise attenuates hyperglycemia induced by type 1 diabetes, improves the lipid prole, and induces changes in the functionality of innate and acquired immunity.

Arquivos Brasileiros de Endocrinologia & Metabologia 57(7):520-528

A relação da microbiota intestinal com obesidade e resistência à insulina.

A  obesidade  é  um  problema  de saúde   pública   e   vem   ocorrendo   aumento rápido  da  sua  prevalência. Esta doença  está associada    a    diversas    morbidades,    como síndrome   metabólica,   diabetes   e   doenças cardiovasculares.    Adicionalmente,     estudos recentes   levantam   a   hipótese   de   que   a  obesidade    pode    estar relacionada    com alterações  da  flora  intestinal.  Neste  sentido, dois  filos  principais  de  bactérias  (Firmicutes  e Bacteroidetes),     encontrados     no     intestino delgado e grosso vêmsendo investigadas. De fato,  evidências  indicam que  desequilíbrio  nas proporções destas populações pode levar  não apenas    a    obesidade,    mas    também    à resistência   a   insulina.   Objetivo:   Analisar   a relação das bactérias Firmicutes e Bacteroidetes  encontradas  na  flora intestinal com   o   aumento   de   peso   e   resistência   a insulina.    Materiais    e    métodos:    Revisão bibliográfica  a partir  de  artigos  das  bases  de dados  e  sites  específicos  da  área  da  saúde, publicados   a   partir   de   2002.   Revisão   de literatura:   Foram   avaliadas   as   relações   da microbiota   intestinal   com   a   obesidade   e resistência  a insulina  em  ratos  e  humanos. Conclusão:   A   flora   intestinal   do   obeso   é diferente a do magro, tanto em humanos como em  ratos  e  esta  flora  esta  relacionada  com  a obesidade  e  resistência  a  insulina.  Existem alterações nos filos das bactérias Firmicutes e Bacteroidetes em relação a obesos e magros.

Revista Brasileira de Obesidade, Nutrição e Emagrecimento, São Paulo v.6, n.31, p.31-34, Jan/Fev. 2012. ISSN 1981-9919

O papel da suplementação de L-arginina sobre parâmetros bioquímicos e funcionais em individuos saudáveis e portadores de doenças crônicas não transmissíveis

A Síndrome Metabólicaé acompanhada  de inflamação   e   disfunção   endotelial,   a   qual caracteriza-se por alteração na capacidade de relaxamento    vascular,    devido    a    reduzida biodisponibilidade  de  fatores  de  relaxamento, como  o óxido  nítrico  (NO).  O  aminoácido  L-arginina   é   um   precursor   de   NO   e   sua suplementação pode modular a capacidade de dilatação   vascular   e   diminuir   síntese   de glicose.    Objetivo:   Analisar    os    efeitos    da suplementação  de  L-arginina  sobre  o  perfil lipídico,     resistência     à     insulina,     ADMA, adiponectina,  PCR,  PA, IMC,  CA  e  função endotelial em indivíduos saudáveis e portadores de doenças crônicas não transmissíveis.  Materiais  e  métodos:  Revisão bibliográfica  a  partir  de  artigos  das  bases  de dados  e  sites  específicos  da  área  da  saúde, publicados   a   partir   de   1998.   Revisão   de literatura:   Foram   avaliados   os   efeitos   da suplementação     de     L-arginina     sobre     as variáveis    mencionadas    anteriormente    em indivíduos saudáveis e portadores de doenças crônicas não transmissíveis. Conclusão: O uso de   L-arginina   em   dosagens   superiores   a 9g/dia   ou   abaixo   de   6,5g/dia   parece   não proporcionar    resultados    significativos    nas variáveis investigadas. Pesquisas que obtiveram resultados positivos com o uso de L-arginina   em   dosagens   abaixo   de   6,5g/dia estavam   associadas   a   outros   suplementos, impossibilitando correlacionar tais resultados a um  efeito  independente  de  L-arginina.  O  uso de   dosagens   superiores   a   9g/dia,   mesmo quando associadas a outros suplementos, não proporciona  resultados significativos  sobre  as variáveis investigadas.

Revista Brasileira de Obesidade, Nutrição e Emagrecimento, São Paulo v.6, n.31, p.35-45, Jan/Fev. 2012. ISSN 1981-9919

Efeito do treinamento combinado em indivíduo hipertenso, com sobrepeso, pós-ablação de síndrome de Wolff-Parkinson-White, sobre fatores que desencadeiam fibrilação atrial.

A prática de exercício tem sido recomendada como principal agente no tratamento da Fibrilação Atrial, por reduzir o peso, controlar a hipertensão arterial e assim diminuir sua ação. Tem como objetivo verificar os efeitos de programa de treinamento combinado um indivíduo com sobrepeso, hipertenso, pós-ablação da Síndrome de Wolff-Parkinson-White, sobre fatores que desencadeiam a Fibrilação Atrial. O treino foi realizado num período de 3 meses, e o individuo se submeteu a um treinamento aeróbio e de resistência em intensidade moderada. Verificou-se uma boa evolução do individuo com redução do IMC de 26,1 para 23,6. A Pressão Arterial foi observada durante todo o período e notou-se uma leve redução a níveis consideráveis onde, o individuo não se sentiu mal, durante ou mesmo depois do exercício. Com isso conclui-se que o treinamento combinado e de intensidade moderada exerce sim efeito significativo na diminuição do peso e no controle da fibrilação atrial.

FIEP BULLETIN - Volume 82 – Special Edition - ARTICLE II

Fish oil supplementation reduces cachexia and tumor growth while improving renal function in tumor-bearing rats.

The objective of the present work was to study the renal function of healthy and tumor-bearing rats chronically supplemented with fish oil (FO), a source of n-3 polyunsaturated fatty acids. Weanling male rats were divided in two groups, one control (C) and another orally supplemented for 70 days with FO (1 g/kg body weight). After this time, half the animals of each group were injected in the right flank with a suspension of Walker 256 tumor cells (W and WFO). The W group had less proteinemia reflecting cachectic proteolysis, FO reversed this fact. Tumor weight gain was also reduced in WFO. Glomerular filtration rate (GFR) was not different in FO or W compared to C, but was higher in WFO. Renal plasma flow (RPF) was higher in the FO supplemented groups. The W group had lower plasma osmolality than the C group, but FO supplementation resulted in normalization of this parameter. Fractional sodium excretion (FE(Na+)) of FO rats was similar to C. Proximal Na(+) reabsorption, evaluated by lithium clearance, was similar among the groups. Urinary thromboxane B(2) (TXB(2)) excretion was lower in the supplemented groups. The number of macrophages in renal tissue was higher in W compared to C rats, but was lower in WFO rats compared to W rats. In conclusion, FO supplementation resulted in less tumor growth and cachexia, and appeared to be renoprotective, as suggested by higher RPF and GFR.

Lipids. 2012 Nov;47(11):1031-41. doi: 10.1007/s11745-012-3715-9. Epub 2012 Sep 27

Fish Oil Supplementation Improves Neutrophil Function During Cancer Chemotherapy.

Cancer chemotherapy is associated with neutropenia and impaired neutrophil function. This study aimed to investigate whether supplementation with low dose fish oil (FO), providing n-3 polyunsaturated fatty acids, in cancer patients receiving chemotherapy after surgical tumor (mainly gastrointestinal) removal is able to improve the function of blood neutrophils. Patients (n = 38) receiving chemotherapy (5-fluorouracil and leucovorin) were randomized into two groups; one group (control) did not receive a supplement, while the other group (FO) received 2 g FO/day for 8 weeks; the FO provided 0.3 g eicosapentaenoic acid plus 0.4 g docosahexaenoic acid per day. Patients in the control group lost an average of 2.5 kg of weight over the 8 weeks of the study. The number of blood polymorphonuclear cells (PMNC), mainly neutrophils, and their functions (phagocytosis and hydrogen peroxide production) decreased in the control group (average decreases of approximately 30, 45 and 17%, respectively). FO prevented these decreases and actually increased body weight (average of 1.7 kg weight gain; p < 0.002 vs. control group), PMNC number (average 29% increase), phagocytosis (average 14% increase) and superoxide production (average 28% increase). FO may be useful in preventing chemotherapy-induced decline in neutrophil number and function.

Lipids. 2012 Apr;47(4):383-9. doi: 10.1007/s11745-011-3643-0

Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats. 

Background: Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats.

Methods: Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed.

Results: Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob.

Conclusions: Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

Lipids Health Dis. 2011 Apr 28;10:66. doi: 10.1186/1476-511X-10-66

Tumor growth reduction in Walker 256 tumor-bearing rats performing anaerobic exercise: participation of Bcl-2, Bax, apoptosis, and peroxidation.

Physical activity has been used in cancer prevention and treatment. In this study, we investigated some of the mechanisms by which anaerobic exercise reduces tumor growth. To do so, rats were trained for 8 weeks. Training consisted of jumping in a swimming pool for ten 30-s sets, with a load that was 50% of body weight attached to the back, 4 times per week. At the sixth week, anaerobic exercise trained rats (EX group) were inoculated with a suspension of Walker 256 tumor cells. Tumor weight, apoptotic tumor cells, tumor Bax and Bcl-2 protein expression, tumor lipid peroxidation, and tumor cell proliferation ex vivo were evaluated. Tumor weight was significantly lower in the EX group (∼30%) than in rats that did not undergo training (sedentary group) (p < 0.05). Apoptosis in the tumor cells of EX rats was 2-fold higher than in the tumor cells of sedentary rats; in addition, Bax expression increased by 10% and Bcl-2 decreased by 13% in EX rats. Lipid peroxidation was 4-fold higher in the tumor cells of EX rats than in those of sedentary rats (p < 0.05). Tumor cell proliferation ex vivo was 29% lower in the EX group than in the sedentary group (p < 0.05). In conclusion, Walker 256 tumor-bearing exercised rats presented more tumor cell apoptosis, a higher tumor content of lipid peroxides, pro-apoptotic protein expression balance, and reduced tumor weight and cell proliferation ex vivo, compared with sedentary rats. These events, together, account for the lower tumor growth we observed in the EX rats.

Appl Physiol Nutr Metab. 2011 Aug;36(4):533-8. doi: 10.1139/h11-047

Chronic Supplementation With Shark Liver Oil for Reducing Tumor Growth and Cachexia in Walker 256 Tumor-Bearing Rats.

We investigated the effect of chronic supplementation with shark liver oil (SLO), an antitumor supplement source of n-3 fatty acids and 1-O-alkylglycerols, alone and combined with coconut fat (CF), a source of saturated fatty acids, on Walker 256 tumor growth and cachexia. Male rats were supplemented daily and orally with SLO and/or CF (1 g per kg body weight) for 7 wk. After 7 wk, 50% of animals were subcutaneously inoculated with 3 × 107 Walker 256 tumor cells. After 14 days, the rats were killed, the tumors were removed for lipid peroxidation measurement, and blood was collected for glycemia, triacylglycerolemia, and lacticidemia evaluation. Liver samples were obtained for glycogen measurement. Unlike CF, supplementation with SLO promoted gain in body weight, reduction of tumor weight, and maintained glycemia, triacylglycerolemia, lacticidemia, and liver glycogen content to values similar to non-tumor-bearing rats. Combined supplementation of SLO with CF also showed a reversion of cachexia with gain in body mass, reduction of lacticidemia, maintaining the liver glycogen store, and reduction in tumor weight. SLO, alone or combined with CF, promoted increase of tumor lipid peroxidation. In conclusion, SLO supplemented chronically, alone or associated with CF, was able to reduce tumor growth and cachexia.

Nutr Cancer. 2011 Nov;63(8):1307-15. doi: 10.1080/01635581.2011.607540

Lymphocytes transfer [14C]-labeled fatty acids to skeletal muscle in culture; modulation by exercise. 

Previous studies have shown that lipids are transferred from lymphocytes (Ly) to different cell types including macrophages, enterocytes, and pancreatic beta cells in co-culture. This study investigated whether [(14)C]-labeled fatty acids (FA) can be transferred from Ly to skeletal muscle (SM), and the effects of exercise on such phenomenon. Ly obtained from exercised (EX) and control (C) male Wistar rats were preloaded with the [(14)C]-labeled free FA palmitic (PA), oleic (OA), linoleic (LA), or arachidonic (AA). Radioactively loaded Ly were then co-cultured with SM from the same Ly donor animals. Substantial amounts of FA were transferred to SM being the profile PA = OA > AA > LA to the C group, and PA > OA > LA > AA to the EX group. These FA were incorporated predominantly as phospholipids (PA = 66.75%; OA = 63.09%; LA = 43.86%; AA = 47.40%) in the C group and (PA = 63.99% OA = 52.72%; LA = 55.99%; AA = 63.40%) in the EX group. Also in this group, the remaining radioactivity from AA, LA, and OA acids was mainly incorporated in structural and energetic lipids. These results support the hypothesis that Ly are able to export lipids to SM in co-culture. Furthermore, exercise modulates the lipid transference profile, and its incorporation on SM. The overall significance of this phenomenon in vivo remains to be elucidated.

Cell Biochem Funct. 2010 Jun;28(4):278-82. doi: 10.1002/cbf.1652

Beta-hydroxy-beta-methylbutyrate supplementation reduces tumor growth and tumor cell proliferation ex vivo and prevents cachexia in Walker 256 tumor-bearing rats by modifying nuclear factor-kappaB expression.

Cancer cachexia syndrome contributes to wasting and weight loss leading to inefficacy of anticancer therapy. In this study, the anticatabolic agent beta-hydroxy-beta-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Male Wistar rats were randomly assigned to nontumor and tumor-bearing groups and fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight). Beta-hydroxy-beta-methylbutyrate supplementation induced a lower tumor weight and tumor cell proliferation ex vivo, totally prevented glycemia reduction, as well as blunted the increase in the serum lactate concentrations and also preserved glycogen stores in tumor-bearing rats. Reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-kappaB inhibitor-alpha content by more than 100%. In contrast, nuclear factor-kappaB p65 subunit content was suppressed by 17% with HMB supplementation. In conclusion, HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-kappaB pathway participation, which might be a potential nutritional strategy in cancer therapy.

Nutr Res. 2008 Jul;28(7):487-93. doi: 10.1016/j.nutres.2008.04.006

Neutrophil response of anaerobic jump trained diabetic rats. 

This paper investigated the effect of jump training on blood biochemical parameters and neutrophil responses of diabetic rats. Male Wistar rats were divided into control, trained, diabetic and trained-diabetic groups. Diabetes was induced by i.v. injection of streptozotocin. Jump training consisted of six sets of ten jumps in water with overload of 50% of body mass with 1-min of resting, four times per week during 6 weeks. Plasma glucose, lactate, triacylglycerol and total cholesterol concentrations, differential leukocyte count, phagocytosis and anion superoxide production by neutrophils were evaluated. Diabetes caused hyperglycemia, hypertriacylglycerolemia, and body weight loss. Physical training reversed hypertriacylglycerolemia. Jump training increased phagocytosis and anion superoxide production by blood neutrophils from trained and trained-diabetic rats. Neutrophilia and lymphocytopenia occur in diabetic and trained-diabetic rats. Anaerobic jump training in diabetic rats reduced hypertriacylglycerolemia and increased neutrophil anion superoxide production. Phagocytosis was not altered in trained-diabetic rats.

Eur J Appl Physiol. 2008 Dec;104(6):1079-86. doi: 10.1007/s00421-008-0865-9

Glucose metabolism by lymphocytes, macrophages, and tumor cells from Walker 256 tumor-bearing rats supplemented with fish oil for one generation. 

Here we investigated the effect of lifelong supplementation of the diet with coconut fat (CO, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) on tumor growth and lactate production from glucose in Walker 256 tumor cells, peritoneal macrophages, spleen, and gut-associated lymphocytes. Female Wistar rats were supplemented with CO or FO prior to mating and then throughout pregnancy and gestation and then the male offspring were supplemented from weaning until 90 days of age. Then they were inoculated subcutaneously with Walker 256 tumor cells. Tumor weight at 14 days in control rats (those fed standard chow) and CO supplemented was approximately 30 g. Supplementation of the diet with FO significantly reduced tumor growth by 76%. Lactate production (nmol h(-1) mg(-1) protein) from glucose by Walker 256 cells in the group fed regular chow (W) was 381.8 +/- 14.9. Supplementation with coconut fat (WCO) caused a significant reduction in lactate production by 1.6-fold and with fish oil (WFO) by 3.8-fold. Spleen lymphocytes obtained from W and WCO groups had markedly increased lactate production (553 +/- 70 and 635 +/- 150) when compared to non-tumor-bearing rats ( approximately 260 +/- 30). FO supplementation reduced significantly the lactate production (297 +/- 50). Gut-associated lymphocytes obtained from W and WCO groups increased lactate production markedly (280 +/- 31 and 276 +/- 25) when compared to non-tumor-bearing rats ( approximately 90 +/- 18). FO supplementation reduced significantly the lactate production (168 +/- 14). Lactate production by peritoneal macrophages was increased by tumor burden but there was no difference between the groups fed the various diets. Lifelong consumption of FO protects against tumor growth and modifies glucose metabolism in Walker tumor cells and lymphocytes but not in macrophages.

Cell Biochem Funct. 2008 Dec;26(8):874-80. doi: 10.1002/cbf.1520

Efeitos distintos da ingestão de frutose e glicose sobre a ressíntese de glicogênio muscular e hepático após exercício em ratos submetidos a treinamento de natação.

A restauração dos estoques de glicogênio hepático e muscular é parte importante do processo de recuperação após o exercício. Um dos fatores relacionados à ressíntese ótima do glicogênio hepático ou muscular, pode ser o tipo de carboidrato ingerido. Este trabalho investigou o efeito de diferentes carboidratos (glicose ou frutose), ingeridos após o exercício, sobre a ressíntese do glicogênio hepático e muscular. Cinqüenta ratos Wistar machos foram divididos em cinco grupos: Sedentário (S), Exercitado controle (EC), Exercitado com água (EA), Exercitado com glicose (EG) e Exercitado com frutose (EF). Os grupos EC, EA, EG e EF foram submetidos a trinta minutos de natação, três vezes por semana durante nove semanas, com sobrecarga igual a 8% do peso do indivíduo acoplado ao tórax. No último dia do treinamento os grupos EG e EF receberam solução 8% (0,7g/kg/h), contendo glicose ou frutose, logo após o término da sessão e uma segunda administração uma hora depois. Os grupos S, EC e EA receberam apenas água. Os indivíduos foram ortotanasiados uma hora após a segunda administração. Amostras de tecido hepático, dos músculos sóleo e gastrocnêmio foram coletadas para determinação do conteúdo de glicogênio. Em adição foi coletado sangue para se mensurar a glicemia. O grupo EF apresentou conteúdo de glicogênio hepático 35% maior quando comparado ao do grupo EG. No entanto, o grupo EG apresentou maior conteúdo de glicogênio no sóleo quando comparado ao do grupo EF (1,08 ± 0,09 vs. 0,63 ± 0,06 mg/100mg de tecido; P<0,05) e também no gastrocnêmio (2,02 ± 0,40 vs. 0,95 ± 0,19 mg/100mg de tecido; P<0,05). O tipo de carboidrato ingerido após a atividade física, influenciou na reposição do glicogênio hepático e muscular, sendo que a glicose foi o substrato mais eficaz para a ressíntese de glicogênio muscular e a frutose para a recuperação do glicogênio hepático.

Estud Biol. 2008 jan/dez;30(70/71/72):35-45 doi: 10.7213/reb.v30i70/72.22802

Glutamine concentration and immune response of spinal cord injured rats.

Background/objectives: Glutamine plays a key role in immune response. Spinal cord injury (SCI) leads to severe loss of muscle mass and to a high incidence of infections. This study investigated the acute effect of SCI (2 and 5 days) on the plasma glutamine and skeletal muscle concentrations and immune responses in rats.

Methods: A total of 29 adult male Wistar rats were divided as follows: control (C; n = 5), sham-operated (S2; n = 5) and spinal cord-transected (T2; n = 7). They were killed on day 2 after surgery/transection (acute phase). Another set was sham-operated (S5; n = 5), spinal cord-transected (T5; n = 7), and killed at day 5 after surgery/transection (secondary phase). Blood was collected; the white portion of the epitrochlearis and gastrocnemius muscles and the red portion of soleus muscles were dissected to measure the glutamine concentration. Gut-associated lymphocytes and peritoneal macrophages were obtained for immune parameters measurements.

Results: Glutamine concentration in the plasma, gastrocnemius, and soleus muscles in rats with SCI were significantly reduced but not in the epitrochlearis muscle in the acute (2 days) and secondary (5 days) phases. Phagocytic response was reduced in the acute phase but increased in the secondary phase in rats with SCI. Superoxide production, on the other hand, was significantly increased at days 2 and 5 after SCI, and CD8+ lymphocytes subset decreased significantly on days 2 and 5.

Conclusions: Our results showed reduction in plasma glutamine and skeletal muscle concentrations after spinal cord transection. They also suggest that SCI and glutamine reduction contribute to an alteration in immune competence.

J Spinal Cord Med. 2007;30(2):140-6. doi: 10.1080/10790268.2007.11753925