Short-term high-fat diet affects macrophages inflammatory response, early signs of a long-term problem

Obesity is a chronic inflammatory disease that affects millions of people worldwide. Most studies observe the effects of a high-fat diet (HFD) in 10-12 weeks. This work investigated the effects induced by a HFD administered for 6 weeks on the nutritional status of mice and some aspects of the inflammatory response in mouse peritoneal macrophages. Male Swiss Webster mice, 2-3 months of age, were fed a control diet or HFD for 6 weeks. After this period, the mice were euthanized, and peritoneal macrophages were collected for immunoassays and assessment of biochemical parameters. A HFD was associated with increased cholesterol, insulin resistance, C-reactive protein (CRP), leptin, and serum resistin levels. Lipopolysaccharide (LPS)- stimulated adipocyte cultures of animals subjected to a HFD showed increased production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6). However, peritoneal macrophages of the HFD group showed no changes in the levels of these cytokines. LPS-stimulated peritoneal macrophages from HFD-treated animals showed a reduction in mRNA expression of TNF-α and IL-6, as well as a decrease in expression of the transcription factor nuclear factor-kappa B (NF-kB). In conclusion, HFD treatment for 6 weeks induces similar signs to metabolic syndrome and decreases the capacity of peritoneal macrophages to develop an appropriate inflammatory response to a bacterial component

Correction to: High-fat diet or low-protein diet changes peritoneal macrophages function in mice

The original version of this article [1], published on 28 June 2016, contains a mistake. The part labels in Fig. 1 are missing. The corrected version of Fig. 1 is given below.

Glutamine metabolism and its effects on immune response: molecular mechanism and gene expression

This article aims to review glutamine metabolism and its effects on the immune response. Selected topics are addressed, particularly the effect of glutamine on cell survival and proliferation, as well as its importance in some biochemical pathways. The impact of glutamine on muscle, intestine, and liver metabolism are described, and a special section about glutamine regulation of the immune response is included. In this context, the modulation of glutamine on relevant signaling pathways as nuclear factor kappa B (NF-kB), mitogen-activated protein kinases (MAPKs), and heat shock protein and the influence of this amino acid on cell migration and adhesion molecules are highlighted. Some important immune response pathways modulated by glutamine were described as its action incritically ill patients. In summary, this review describes some important actions of glutamine, and a range of reactions and modulatory effects in different organs, which may inform new therapeutic strategies. However, further studies are necessary to provide information about glutamine use, especially about situations in which it can be better used as well as fine-tuning dose and administration.

High-fat diet or low-protein diet changes peritoneal macrophages function in mice

BACKGROUND: Obesity and protein malnutrition are major food problems nowadays, affecting billions of people around the world. The nutrition transition that has occurred in recent decades is changing the nutritional profile, reducing malnutrition and increasing the percentage of obese people. The innate immune response is greatly influenced by diet, with significant changes in both malnutrition and obesity. Therefore, we investigate the effects of protein malnutrition and obesity in nutritional and immunological parameters in mice. RESULTS: Peritoneal macrophages of malnourished animals showed reduced functions of adhesion, spreading, and fungicidal activity; production of hydrogen peroxide and nitric oxide were lower, reflecting changes in the innate immune response. However, the high-fat animals had macrophage functions slightly increased. CONCLUSIONS: Animals subjected to low-protein diet have immunosuppression, and animals subjected to high-fat diet increased visceral adipose tissue and the presence of an inflammatory process with increased peritoneal macrophage activity and similar systemic changes to metabolic syndrome.

The influence of protein malnutrition on the production of GM-CSF and M-CSF by macrophages

ABSTRACT It is well established that protein malnutrition (PM) impairs immune defenses and increases susceptibility to infection. Macrophages are cells that play a central role in innate immunity, constituting one of the first barriers against infections. Macrophages produce several soluble factors, including cytokines and growth factors, important to the immune response. Among those growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). GM-CSF and M-CSF are important to monocyte and macrophage development and stimulation of the immune response process. Knowing the importance of GM-CSF and M-CSF, we sought to investigate the influence of PM on macrophage production of these growth factors. Two-month-old male BALB/c mice were subjected to PM with a low-protein diet (2%) and compared to a control diet (12%) mouse group. Nutritional status, hemogram and the number of peritoneal cells were evaluated. Additionally, peritoneal macrophages were cultured and the production of GM-CSF and M-CSF and mRNA expression were evaluated. To determine if PM altered macrophage production of GM-CSF and M-CSF, they were stimulated with TNF-α. The PM animals had anemia, leukopenia and a reduced number of peritoneal cells. The production of M-CSF was not different between groups; however, cells from PM animals, stimulated with or without TNF-α, presented reduced capability to produce GM-CSF. These data imply that PM interferes with the production of GM-CSF, and consequently would affect the production and maturation of hematopoietic cells and the immune response.

Hematological and biochemical reference values for C57BL/6, Swiss Webster and BALB/c mice / Valores de referência hematológicos e bioquímicos para camundongos das linhagens C57BL/6, Swiss Webster e BALB/c

The use of animals in scientific research has contributed significantly to the development of science, promoting various advances in understanding the metabolic machinery and the discovery of treatments and preventive measures applied to human and veterinary medicine. The development and use of alternative methods is encouraged; however, in some situations, the use of animals in accordance with ethical policies is still required. Established hematological and clinical chemistry reference values in laboratory animals are essential to evaluate functional changes; however, there are few data in the literature on these values, being fundamentally a comparative basis. The aim of this investigation was the establishment of hematological and clinical chemistry reference values in common strains/stocks of mice used in animal experimentation. Blood profile (hemogram, reticulocytes and myelogram) and clinical chemistry serum determination of total protein, albumin, glucose, cholesterol, triglycerides, calcium and phosphorus were evaluated using C57BL/6, BALB/c and Swiss Webster mice, male, 2-3 months old. The results standardize reference intervals in animals reared in Laboratory Animal Facility, reflecting the expected condition in rodents subjected to scientific research...

O uso de animais na pesquisa científica tem contribuído significativamente para o desenvolvimento da ciência, promovendo vários avanços na compreensão da maquinaria metabólica, bem como a descoberta de tratamentos e medidas preventivas aplicadas à medicina humana e veterinária. O desenvolvimento e utilização de métodos alternativos é encorajado, no entanto, em algumas situações, ainda é necessária a utilização de animais em conformidade com termos éticos. Estabelecer valores de referência hematológicos e bioquímicos para animais de laboratório é essencial para avaliar alterações funcionais, no entanto, existem poucos dados na literatura sobre estes valores, sendo fundamentalmente uma base comparativa. O presente trabalho foi delineado para estabelecer valores de referência hematológicos e bioquímicos em linhagens camundongos utilizados em pesquisa científica. Foram avaliados o perfil sanguíneo (hemograma, reticulócitos e mielograma) e a determinação bioquímica sérica de proteínas totais, albumina, glicose, colesterol, triglicerídeos, cálcio e fósforo. Foram utilizados camundongos C57BL/6, BALB/c e Swiss Webster, do sexo masculino, 2-3 meses de idade. Os resultados padronizam intervalos de referência em camundongos criados em Biotério, refletindo a condição esperada nesses animais submetidos à investigação científica...

Produção de peróxido de hidrogênio e atividade de enzimas antioxidantes de macrófagos peritoneais em resposta ao BCG (Bacilo de Calmette-guérin) em modelo murínico de desnutrição proteico-energética / Hydrogen peroxide production and activity of antioxidant enzymes of peritoneal macrophages in response to BCG (Bacillus Calmette-guérin) in a murine model of protein-energy malnutrition

units of BCG (Bacillus Calmette-guérin) and after 7 days they were used in the experiments. We evaluated the complete blood count, peritoneal cellularity and hydrogen peroxide production, besides the activities of glutathione peroxidase, superoxide dismutase and catalase in peritoneal macrophages stimulated with BCG. Malnourished animals presented anemia, leukopenia and severe reduction of peritoneal cellularity. The production of hydrogen peroxide and the activity of glutathione peroxidase, superoxide dismutase and catalase were found to be significantly lower in macrophages from malnourished animals. These findings suggest that malnourished animals present a deficient response to BCG. These findings may be partly responsible for a decrease in the bactericidal and fungicidal activities observed in the malnourished mice. These data lead us to infer that the nutritional status interferes with the activation of macrophages and with the capacity tomount an immune response.Protein-energy malnutrition (PEM) modifies resistance to infection, impairing a number of physiological processes, changing specific and nonspecific immune responses. Macrophages, which are directly involved in several aspects of immunity, may have their functions altered in the malnourishment condition, possibly playing a significant role in the immune deficiency observed in malnourished individuals. Two-month-old male Swiss mice were induced to PEM with a low-protein diet containing 4% protein as compared to 20% protein in the control diet. When the experimental group had lost about 20% of their original body weight the animals from both groups received intraperitoneal injections of 10

unidades de BCG (Bacilo de Calmetteguérin), por vía intraperitoneal, y después de 7 días los animales fueron sacrificados para evaluación de diversos índices: hemograma, celularidad peritoneal, la producción deperóxido de hidrógeno y las actividades glutatión peroxidada, superóxido dismutasa, y catalasa en macrófagos peritonea les estimulados con BCG. Los animales subalimentados presentaron anemia, leucopenia y reducción de la celularidad peritoneal. La producción de peróxido de hidrógeno y la actividad de las enzimas glutatión peroxidada, superóxido dismutasa, y catalasa fue más baja en macrófagos de animales desnutridos. Los resultados sugieren que los ratos desnutridos presentan una respuesta deficiente a BCG lo que explica en parte la disminución de la actividad bactericida y fungicida observada en animales desnutridos. Estos resultados permiten deducir que el estado nutricional interfiere en la actividad de los macrófagos y en su capacidadde respuesta inmunológica.La desnutrición proteico-energética modifica la resistencia a infecciones, alterando diversos procesos fisiológicos, mudando la capacidad de respuesta inmune, específica y no específica. Los macrófagos, células implicadas directamente en varios aspectos de la inmunidad, pueden tener sus funciones alteradas en condiciones de desnutrición desempeñando posiblemente un papel significativo en la deficiencia inmune observada en individuos desnutridos. En este estudio se utilizaron ratos Swiss machos, de 2 meses de edad, en los cuales fue inducida desnutrición proteico-energética por mediode una dieta que contenía 4% de proteína. El grupo control recibió una dieta estándar con 20% de proteína. Cuando el grupo experimental presentó una pérdida de 20% desu peso corporal original, se le administraron 10

unidades de BCG (Bacilo de Calmetteguérin) e após 7 dias foram sacrificados e utilizados nos experimentos. Avaliamos o hemograma, a celularidade peritoneal assim como a produção de peróxido de hidrogênio e a atividade da glutationa peroxidase, superóxido dismutase e catalase em resposta ao BCG em macrófagos peritoneais. Os animais desnutridos apresentaram anemia, leucopenia e a redução severa da celularidade peritoneal. A produção de peróxido de hidrogênio e a atividade das enzimas glutationa peroxidase, super óxido dismutase e catalase foi significativamente menor nos macrófagos de animais desnutridos. Estes resultados sugerem que os animais desnutridos apresentem uma resposta deficiente ao BCG, e que, em parte, podem explicar a diminuição nas atividades bactericidas e fungicidas observadas em animais desnutridos. Estes dados permitem deduzir que o estado nutricional interfere na ativação dos macrófagos e na sua capacidadede resposta imune.A desnutrição proteico-energética (DPE) altera a capacidade de resistência à infecção, alterando diversos processos fisiológicos, mudando a capacidade de respostas imunes específicas e não específicas. Os macrófagos são células envolvidas diretamente em diversos aspectos da imunidade, podem ter suas funções alteradas em condições de desnutrição desempenhando, possivelmente, um papel significativo na imunodeficiência observada nesses indivíduos. Camundongos Swiss, machos, de dois meses de idade, foram induzidos a DPE com uma dieta contendo baixa concentração deproteína (4%) em comparação à dieta controle (20%). Quando o grupo experimental perdeu aproximadamente 20% de seu peso corpóreo original, estes foram considerados aptos aos experimentos. Animais de ambos os grupos receberam injeção intraperitoneal contendo10

Protein-energy malnutrition alters the C3 complement factor in response to lipopolysaccharide in a murine model / A desnutrição proteico-energética altera a concentração do fator C3 do sistema complemento em resposta ao lipopolissacarídeo em um modelo murínico

Malnutrition modifies the hostfis resistance to infection, altering many physiological processes, including hematopoiesis and immunological functions. In this study, we evaluated the total complement system and its C3 component factor in animals subjected to a protein malnutrition model with lipopolysaccharide (LPS) stimulation. The cellularity of blood, bone marrow and spleen, as well as the production of C3 and CH50, were evaluated. Two-month old male Swiss mice were submitted to protein malnutrition with a low-protein diet containing 4% protein. A control group received a control diet containing 20% protein. When the experimental group had reached a loss of about 20% in their original body mass, they were intravenously inoculated with LPS. Cells in the blood, bone marrow and spleen were counted and the circulating levels of C3 and CH50 were evaluated in these animals. Malnourished animals presented anemia, leucopenia, and a severe reduction in bone marrow and spleen cellularity. The survival rate of the malnourished animals was lower, as well as the production of C3 and CH50, if compared to the control animals. These findings suggest that malnourished mice present a deficient response to LPS. The decrease in the complement synthesis may be partially responsible for the immunodeficiency observed. These data lead us to conclude that the nutritional status interferes in the immune response activation.

La desnutrición proteico-energética modifica la resistencia a la infección, alterando numerosos procesos fisiológicos, incluyendo la hematopoyesis y la función inmunológica. En este estudio medimos las concentraciones séricas del factor C3 y del Sistema Complemento Total (CH50) en ratos con desnutrición proteico-energética estimulados con lipopolisacárido (LPS). Fue evaluada la celularidad periférica, medular y esplénica. Ratos Swiss, machos, adultos, con dos meses de edad fueron sometidos a desnutrición proteica con una dieta de 4% de proteína .El grupo control consumía una dieta con 20% de proteínas. Cuando los animales desnutridos perdieron 20% de su peso inicial, fueron inoculados por vía endovenosa con LPS. Fueron determinadas las concentraciones de células sanguíneas, de la médula ósea, del bazo y los valores de C3 y CH50 circulantes en los animales estimulados. Los animales desnutridos presentaron anemia y leucopenia además de una reducción significativa de celularidad de la médula ósea y del bazo. La sobrevivencia de este grupo era menor y también eran más bajas las concentraciones del factor C3 del complemento y del complemento total, en relación a los animales del grupo control. Los resultados sugieren que animales desnutridos muestran una respuesta deficiente a LPS. La síntesis menor de complemento puede ser en parte responsable por la inmunodeficiencia observada. Estos resultados nos conducen a inferir que la desnutrición proteico-energética interfiere en la activación de la respuesta inmune.

A desnutrição proteico-energética modifica a resistência à infecção, modi? cando diversos processos fisiológicos, incluindo a hematopoiese e as funções imunológicas. Neste estudo, avaliamos as concentrações séricas do fator C3 e do Sistema Complemento total (CH50) em um modelo no qual camundongos submetidos à desnutrição proteico-energética são estimulados com lipopolissacarídeo (LPS), e avaliamos a celularidade periférica, medular e esplênica. Camundongos Swiss, machos, adultos, com dois meses de idade foram submetidos ao processo de desnutrição proteica com uma dieta contendo 4% de proteína em comparação aos animais controles com uma dieta contendo 20% de proteína. Quando os animais do grupo desnutrido alcançaram aproximadamente 20% de perda de peso, em relação ao inicial, foram inoculados endovenosamente com LPS. As células do sangue, da medula óssea e do baço foram quantificadas, bem como as concentrações circulantes de C3 e CH50 em animais estimulados com LPS. Os animais desnutridos apresentaram anemia e leucopenia, além de redução significativa da celularidade da medula óssea e do baço. Os animais desnutridos apresentaram menor taxa de sobrevivência, bem como das concentrações do fator C3 do complemento e do complemento total em relação aos animais controles. Estes resultados sugerem que animais desnutridos apresentam uma resposta deficiente aos LPS. A síntese menor do complemento pode ser em parte responsável pela imunodeficiência observada. Estes resultados conduzem-nos a inferir que a desnutrição proteico-energética interfere na ativação da resposta imune.

Avaliação de aspecto da resposta inflamatória desencadeada pelo lipopolissacarídeo (LPS) em desnutrição protéica experimental. Quantificação dos receptores de LPS (CD/TLR-4) e do fator de transcrição NFcapaB / Evaluation of aspects of the inflammatory answer unchained by the lipopolysaccharide (LPS) in protein malnutrition experimental. Quantification of the receptors of LPS (CD14/TLR-4) and of the transcription factor NFcapB

Sabe-se que a desnutrição modifica a resposta imune específica e inespecífica do organismo frente a agentes infecciosos comprometendo a produção e a função de células info-hemopoéticas, estando associada a modificações da resposta imune, resultando em maior suscetibilidade à infecções, porém os mecanismos exatos que comprometem o sistema imune em estados de desnutrição ainda estão para serem esclarecidos. A literatura relata que aproximadamente 60 por cento das infecções que evoluem para sepse são adquiridas no ambiente hospitalar, envolvendo geralmente bactérias Gram negativas e incidindo especialmente em indivíduos com nutrição inadequada. Considerando tais aspectos e em função da complexidade da interação do estado nutricional e resposta do organismo frente a agentes patogênicos, envolvendo controles celulares e moleculares múltiplos ainda pouco conhecidos, propusemo-nos a estudar alguns aspectos da resposta inflamatória em desnutrição...