As tendências de transição nutricional ocorridas neste século direcionam para uma dieta mais ocidentalizada, a qual, aliada à diminuição progressiva da atividade física, converge para o aumento no número de casos de obesidade em todo o mundo. Isso representa aumento na morbidade e na mortalidade associadas à obesidade, já que esta é fator de risco para várias doenças como diabetes tipo II, hipertensão, doenças cardiovasculares e cálculo na vesícula biliar. A obesidade se apresenta não apenas como problema científico e de saúde pública, porém como grande indústria que envolve o desenvolvimento de fármacos, de alimentos modificados e estratégias governamentais estimulando a prática regular de atividade física e a orientação alimentar a fim de promover melhores hábitos. Assim, o conhecimento das causas e estratégias preventivas da obesidade é o objeto de estudo de pesquisadores de diferentes centros. Esse artigo tem como objetivo rever esses estudos, abordando o aumento na prevalência e incidência da obesidade, doenças relacionadas ao excesso de peso e os tratamentos para redução da gordura corporal.

RESUMOA obesidade já é considerada uma epidemia mundial independente de condições econômicas e sociais. O risco aumentado de mortalidade e morbidade associado à obesidade tem sido alvo de muitos estudos que tentam elucidar os aspectos da síndrome X como conseqüência da obesidade. Esta síndrome é caracterizada por algumas doenças metabólicas, como resistência à insulina, hipertensão, dislipidemia. Está bem estabelecido que fatores genéticos têm influência neste aumento dos casos de obesidade. No entanto, o aumento significativo nos casos de obesidade nos últimos 20 anos dificilmente poderia ser explicado por mudanças genéticas que tenham ocorrido neste espaço de tempo. Sendo assim, os principais fatores envolvidos no desenvolvimento da obesidade têm sido relacionados com fatores ambientais, como ingestão alimentar inadequada e redução no gasto calórico diário. Na tentativa de desencadear obesidade em animais e permitir o estudo desta doença de maneira mais completa, diversos modelos experimentais de obesidade têm sido desenvolvidos. Ainda que não possam ser considerados exatamente iguais aos modelos de obesidade humana, são de grande valor no estudo dos diversos aspectos que contribuem para este excessivo acúmulo de adiposidade e suas conseqüências. Obesity has been reported as a worldwide epidemic independent of economical and social conditions. The possible causes of increased mortality and morbidity associated with obesity have been focused by several studies that attempted to understand the syndrome X, one of the consequences of obesity. This syndrome is characterized by various metabolic disorders such as insulin resistance, hypertension and dyslipidemia. It is widely known that genetic factors influence the prevalence of obesity. However, the increasing rate of obesity over the past 20 years cannot be explained by changes in the gene pool. In this way, the major factors involved in obesity are related to environmental aspects as dietary intake and reduced energy expenditure. In the attempt to develop obesity in animals as a means of carrying out studies related to the condition, many experimental models have been developed. Although these animal models cannot be expected to exactly mimic human obesity, they may still be of great value in studying the mechanisms inducing augmented deposition of fat and its consequences.

Leishmania RNA virus (LRV) has been shown to be a symbiotic component of Leishmania parasites in South America. Nested retro-transcription polymerase chain reaction was employed to investigate LRV1 presence in leishmaniasis lesions from Brazil. In endemic areas of Rio de Janeiro (RJ), no LRV1 infection was observed even with mucosal involvement. LRV1 was only detected in Leishmania (V.) guyanensis cutaneous lesions from the northern region, which were obtained from patients presenting with disease reactivation after clinical cure of their primary lesions. Our results indicated that the severity of leishmaniasis in some areas of RJ, where Leishmania (V.) brazi-liensis is the primary etiological agent, was not associated with Leishmania LRV1 infection.

Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L. infantum in zoonotic VL. Infected dogs develop progressive disease with a large clinical spectrum. A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome. This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil. Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations. By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42). When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups. Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism. All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response. Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ. TNF showed the best negative correlation (r2 = 0.231; p<0.001). Herein we describe impairment on mRNA cytokine expression in leishmania infected dogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture. We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome.

Background Aedes aegypti is the main vector of important arboviruses such as dengue, Zika and chikungunya. During infections mosquitoes can activate the immune pathways Toll, IMD and JAK/STAT to limit pathogen replication.ResultsHere, we evaluate the immune response profile of Ae. aegypti against Sindbis virus (SINV). We analyzed gene expression of components of Toll, IMD and JAK/STAT pathways and showed that a blood meal and virus infection upregulated aaREL2 in a microbiota-dependent fashion, since this induction was prevented by antibiotic. The presence of the microbiota activates IMD and impaired the replication of SINV in the midgut. Constitutive activation of the IMD pathway, by Caspar depletion, leads to a decrease in microbiota levels and an increase in SINV loads.ConclusionTogether, these results suggest that a blood meal is able to activate innate immune pathways, through a nutrient induced growth of microbiota, leading to upregulation of aaREL2 and IMD activation. Microbiota levels seemed to have a reciprocal interaction, where the proliferation of the microbiota activates IMD pathway that in turn controls bacterial levels, allowing SINV replication in Ae. aegypti mosquitoes. The activation of the IMD pathway seems to have an indirect effect in SINV levels that is induced by the microbiota.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-017-2040-9) contains supplementary material, which is available to authorized users.

In the midgut of the mosquito Aedes aegypti, a vector of dengue and yellow fever, an intense release of heme and iron takes place during the digestion of a blood meal. Here, we demonstrated via chromatography, light absorption and mass spectrometry that xanthurenic acid (XA), a product of the oxidative metabolism of tryptophan, is produced in the digestive apparatus after the ingestion of a blood meal and reaches milimolar levels after 24 h, the period of maximal digestive activity. XA formation does not occur in the White Eye (WE) strain, which lacks kynurenine hydroxylase and accumulates kynurenic acid. The formation of XA can be diminished by feeding the insect with 3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl] benzenesulfonamide (Ro-61-8048), an inhibitor of XA biosynthesis. Moreover, XA inhibits the phospholipid oxidation induced by heme or iron. A major fraction of this antioxidant activity is due to the capacity of XA to bind both heme and iron, which occurs at a slightly alkaline pH (7.5-8.0), a condition found in the insect midgut. The midgut epithelial cells of the WE mosquito has a marked increase in occurrence of cell death, which is reversed to levels similar to the wild type mosquitoes by feeding the insects with blood supplemented with XA, confirming the protective role of this molecule. Collectively, these results suggest a new role for XA as a heme and iron chelator that provides protection as an antioxidant and may help these animals adapt to a blood feeding habit.

The major glucose transporter protein expressed in skeletal muscle is GLUT4. Both muscle contraction and insulin induce translocation of GLUT4 from the intracellular pool to the plasma membrane. The intracellular pathways that lead to contraction- and insulin-stimulated GLUT4 translocation seem to be different, allowing the attainment of a maximal effect when acting together. Insulin utilizes a phosphatidylinositol 3-kinase-dependent mechanism, whereas the exercise signal may be initiated by calcium release from the sarcoplasmic reticulum or from autocrine- or paracrine-mediated activation of glucose transport. During exercise skeletal muscle utilizes more glucose than when at rest. However, endurance training leads to decreased glucose utilization during sub-maximal exercise, in spite of a large increase in the total GLUT4 content associated with training. The mechanisms involved in this reduction have not been totally elucidated, but appear to cause the decrease of the amount of GLUT4 translocated to the plasma membrane by altering the exercise-induced enhancement of glucose transport capacity. On the other hand, the effect of resistance training is controversial. Recent studies, however, demonstrated the improvement in insulin sensitivity correlated with increasing muscle mass. New studies should be designed to define the molecular basis for these important adaptations to skeletal muscle. Since during exercise the muscle may utilize insulin-independent mechanisms to increase glucose uptake, the mechanisms involved should provide important knowledge to the understanding and managing peripheral insulin resistance.

Hemoglobin digestion in the midgut of hematophagous animals results in the release of its prosthetic group, heme, which is a pro-oxidant molecule. Heme enzymatic degradation is a protective mechanism that has been described in several organisms, including plants, bacteria, and mammals. This reaction is catalyzed by heme oxygenase and results in formation of carbon monoxide, ferrous ion, and biliverdin IXα. During digestion, a large amount of a green pigment is produced and secreted into the intestinal lumen of A. aegypti adult females. In the case of another blood-sucking insect, the kissing-bug Rhodnius prolixus, we have recently shown that heme degradation involves a complex pathway that generates dicysteinyl-biliverdin IX gamma. The light absorption spectrum of the Aedes purified pigment was similar to biliverdin, but its mobility on a reverse-phase chromatography column suggested a compound less hydrophobic than biliverdin IXα. Structural characterization by ESI-MS revealed that the mosquito pigment is the α isomer of biliverdin bound to two glutamine residues by an amide bond. This biglutaminyl-biliverdin is formed by oxidative cleavage of the heme porphyrin ring followed by two subsequent additions of glutamine residues to the biliverdin IXα. The role of this pathway in the adaptation of this insect vector to a blood-feeding habit is discussed. Keywordsheme; heme oxygenase; biliverdin; detoxification; Aedes aegypti Dengue fever, associated with dengue hemorrhagic fever (DHF), is the most prevalent vectorborne viral disease affecting humans, transmitted mainly by the mosquito Aedes aegypti (1). The ability of A. aegypti females to transmit these viruses from one vertebrate host to another is strictly related to their hematophagous habit. Ingestion of a blood meal triggers intense protein digestion which takes place in the lumen, providing nutrients required for oogenesis (2) but also leading to the release of high amounts of free heme due to host hemoglobin proteolysis. Heme is potentially toxic due to its capacity to promote the generation of reactive oxygen species (ROS) (3). Being an amphiphilic molecule, heme can also insert itself into phospholipid bilayers, leading to destabilization of membrane structure and cell lysis (4). Blood-sucking arthropods present a complex array of heme detoxification and antioxidant mechanisms (5) that allow them to counteract free heme cytotoxicity and adapt to hematophagy. These include heme-binding proteins in the hemolymph of kissing-bugs (6) and ticks (7), high levels of antioxidant enzymes in the midgut of Rhodnius prolixus (8), and aggregation of heme in the midgut of this kissing-bug (9) and ticks (10,11). In A. aegypti, the peritrophic matrix, an extracellular layer that is secreted by the midgut cells and separates the meal from the midgut epithelium, acts as a protective mechanism by binding free heme released during digestion (12). Recently, an Aedes aegypti peritrophin -a protein component of the peritrophic matrix -has been shown to be a heme-binding ...