It is well established that a high-fat diet (HFD) can lead to overweight and ultimately to obesity, as well as promoting low-grade chronic inflammation associated with increased levels of such mediators as TNF-α, IL-1, and IL-6. Bone marrow mesenchymal stem cells (MSCs), which are involved in hematopoietic niches and microenvironments, can be affected by these cytokines, resulting in induction of NF-κB and inhibition of PPAR-γ. Because this phenomenon could ultimately lead to suppression of bone marrow adipogenesis, we set out to investigate the effect of an HFD on the expression of PPAR-γ and NF-κB, as well as the production of IL-1, IL-6, and TNF-α in MSCs. Two-month-old male Wistar rats were fed a HFD diet and evaluated by means of leukograms and myelograms along with blood total cholesterol, triglyceride, and C-reactive protein levels. MSCs were isolated, and PPAR-γ and NF-κB were quantified, as well as IL-1, IL-6, and TNF-α production. Animals that were fed a HFD showed higher levels of blood total cholesterol, triglycerides, and C-reactive protein with leukocytosis and bone marrow hyperplasia. MSCs from HFD animals showed increased production of IL-1, IL-6, and TNF-α and increased NF-κB and reduced PPAR-γ expression. Therefore, ingestion of an HFD induces alterations in MSCs that may influence modulation of hematopoiesis.

-The aim of this study was to investigate whether treatment with tributyrin (Tb; a butyrate prodrug) results in protection against diet-induced obesity and associated insulin resistance. C57BL/6 male mice fed a standard chow or high-fat diet were treated with Tb (2 g/kg body wt, 10 wk) and evaluated for glucose homeostasis, plasma lipid profile, and inflammatory status. Tb protected mice against obesity and obesityassociated insulin resistance and dyslipidemia without food consumption being affected. Tb attenuated the production of TNF␣ and IL-1␤ by peritoneal macrophages and their expression in adipose tissue. Furthermore, in the adipose tissue, Tb reduced the expression of MCP-1 and infiltration by leukocytes and restored the production of adiponectin. These effects were associated with a partial reversion of hepatic steatosis, reduction in liver and skeletal muscle content of phosphorylated JNK, and an improvement in muscle insulin-stimulated glucose uptake and Akt signaling. Although part of the beneficial effects of Tb are likely to be secondary to the reduction in body weight, we also found direct protective actions of butyrate reducing TNF␣ production after LPS injection and in vitro by LPS-or palmitic acid-stimulated macrophages and attenuating lipolysis in vitro and in vivo. The results, reported herein, suggest that Tb may be useful for the treatment and prevention of obesity-related metabolic disorders.butyrate; macrophages; diabetes; cytokines; white adipose tissue THE CHRONIC LOW-GRADE INFLAMMATION associated with obesity plays a central role as a link between excessive fat accumulation and the development of pathologies (20). In obesity, adipose tissue is markedly infiltrated by proinflammatory macrophages and other leukocytes that secrete proinflammatory cytokines and chemokines (20,41,50). The overproduction of these inflammatory mediators together with changes in adipokine production and nonesterified fatty acid (NEFA) levels leads to the development of insulin resistance. In addition to adipose tissue, several organs, including the liver (1) and hypothalamus (28), develop a proinflammatory profile in response to the excessive nutrient supply. This systemic inflammatory state is associated with the activation of intracellular signaling pathways such as JUN NH 2 -terminal kinase (JNK) and IB kinase-␤ (IKK␤) that in turn phosphorylate serine residues in the insulin receptor substrate, inhibiting tyrosine phosphorylation and the interaction with phosphatidylinositol-3 kinase (19,21).In accord with an important role of inflammation in the development of obesity-associated diseases, whole body deletion of intracellular kinases activated upon inflammation, namely JNK (18) and IKK␤ (1), and pharmacological treatment with anti-inflammatory agents such as -3 fatty acids and salsalate, a salicylate derivate, were demonstrated to protect mice from the deleterious effects of high-fat feeding and obesity on insulin sensitivity (16,32).Butyrate is a short-chain fatty acid (SCFA) produced during fermentation o...

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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.