Under physiological conditions, the brain consumes over 20% of the whole body energy supply. The blood-brain barrier (BBB) allows dynamic interactions between blood capillaries and the neuronal network in order to provide an adequate control of molecules that are transported in and out of the brain. Alterations in the BBB structure and function affecting brain accessibility to nutrients and exit of toxins are found in a number of diseases, which in turn may disturb brain function and nutrient signaling. In this review we explore the major advances obtained in the understanding of the BBB development and how its structure impacts on function. Furthermore, we focus on the particularities of the barrier permeability in the hypothalamus, its role in metabolic control and the potential impact of hypothalamic BBB abnormities in metabolic related diseases.

BackgroundThe consumption of large amounts of dietary fats is one of the most important environmental factors contributing to the development of obesity and metabolic disorders. GPR120 and GPR40 are polyunsaturated fatty acid receptors that exert a number of systemic effects that are beneficial for metabolic and inflammatory diseases. Here, we evaluate the expression and potential role of hypothalamic GPR120 and GPR40 as targets for the treatment of obesity.MethodsMale Swiss (6-weeks old), were fed with a high fat diet (HFD, 60% of kcal from fat) for 4 weeks. Next, mice underwent stereotaxic surgery to place an indwelling cannula into the right lateral ventricle. intracerebroventricular (icv)-cannulated mice were treated twice a day for 6 days with 2.0 μL saline or GPR40 and GPR120 agonists: GW9508, TUG1197, or TUG905 (2.0 μL, 1.0 mM). Food intake and body mass were measured during the treatment period. At the end of the experiment, the hypothalamus was collected for real-time PCR analysis.ResultsWe show that both receptors are expressed in the hypothalamus; GPR120 is primarily present in microglia, whereas GPR40 is expressed in neurons. Upon intracerebroventricular treatment, GW9508, a non-specific agonist for both receptors, reduced energy efficiency and the expression of inflammatory genes in the hypothalamus. Reducing GPR120 hypothalamic expression using a lentivirus-based approach resulted in the loss of the anti-inflammatory effect of GW9508 and increased energy efficiency. Intracerebroventricular treatment with the GPR120- and GPR40-specific agonists TUG1197 and TUG905, respectively, resulted in milder effects than those produced by GW9508.ConclusionsGPR120 and GPR40 act in concert in the hypothalamus to reduce energy efficiency and regulate the inflammation associated with obesity. The combined activation of both receptors in the hypothalamus results in better metabolic outcomes than the isolated activation of either receptor alone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0869-7) contains supplementary material, which is available to authorized users.

RESUMO:O cerrado brasileiro é um bioma detentor de grande diversidade biológica. No entanto, são escassas as pesquisas de espécies vegetais, especialmente do cerrado mato-grossense, com potencial para serem utilizadas como filtros solares naturais. O objetivo desta pesquisa foi estudar o potencial fotoprotetor de espécies de diferentes famílias (Apocynaceae, Lythraceae, Oxalidaceae) do cerrado da região do Rio Manso, Chapada dos Guimarães -MT. A absorbância dos extratos etanólicos secos foram medidas em diferentes concentrações entre os comprimentos de onda de 260 a 400nm para verificar a absorção nas regiões ultravioleta A e B (UVA e UVB). As plantas que apresentaram absorbância na região estudada foram submetidas a uma análise fitoquímica qualitativa preliminar para determinar a presença de polifenóis e alcalóides, constituintes característicos de plantas que absorvem a radiação UV. Os extratos etanólicos secos que apresentaram absorção em UVB foram submetidos ao teste de determinação in vitro do Fator de Proteção Solar (FPS) desenvolvido por Mansur. M. Velame apresentou absorção na região UVB com absorbância máxima em 318nm, enquanto que a L. pacari e O. hirsutissima apresentaram absorbância na região UVA. Na concentração utilizada e padronizada, nenhuma das espécies apresentou FPS ≥2, sendo assim não podem ser consideradas plantas com potencial fotoprotetor.Unitermos: Apocynaceae, atividade fotoprotetora, Cerrado de Mato Grosso, fator de proteção solar in vitro, Lythraceae, Oxalidaceae.ABSTRACT: "In vitro sunscreen activity evaluation of plants extracts from Mato Grosso cerrado". The Brazilian savanna is a holding biome of large biological diversity. However, the researches of plants species are scarce, especially at the Mato Grosso´s savanna; which have potential to be used as natural sunscreen. The objective of this research was to study the photoprotector potential of several species (Apocynaceae, Lythraceae, Oxalidaceae) from the savanna´s region at the Manso River, Chapada dos Guimarães -MT. The absorbance of dry ethanolic extracts were measured in different concentrations, between waves from 260nm until 400 nm in length. Just to check the absorption in the A and B ultraviolet regions (UVA and UVB). The plants that presented absorbance by the studied area were submitted to a preliminary qualitative phytochemical analysis to determine if there are polyphenols and alkaloids inside, because they are typical constituents of plants that absorber the UV radiation. The dry ethanolic extracts, that presented absorption in UVB, were submitted to a in vitro Sun Protection Factor (SPF) determination test, developed by Mansur. M.velame presented absorption in the UVB region with maximal absorbance at 318 nm, while L. pacari and O. hirsutissima presented absorbance in the UVA region. At the used and standardized concentration, no species presented SPF ≥ 2, so they cannot be considered plants with photoprotector potential.

In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.

BackgroundDiet-induced hypothalamic inflammation is an important mechanism leading to dysfunction of neurons involved in controlling body mass. Studies have shown that polyunsaturated fats can reduce hypothalamic inflammation. Here, we evaluated the presence and function of RvD2, a resolvin produced from docosahexaenoic acid, in the hypothalamus of mice.MethodsMale Swiss mice were fed either chow or a high-fat diet. RvD2 receptor and synthetic enzymes were evaluated by real-time PCR and immunofluorescence. RvD2 was determined by mass spectrometry. Dietary and pharmacological approaches were used to modulate the RvD2 system in the hypothalamus, and metabolic phenotype consequences were determined.ResultsAll enzymes involved in the synthesis of RvD2 were detected in the hypothalamus and were modulated in response to the consumption of dietary saturated fats, leading to a reduction of hypothalamic RvD2. GPR18, the receptor for RvD2, which was detected in POMC and NPY neurons, was also modulated by dietary fats. The substitution of saturated by polyunsaturated fats in the diet resulted in increased hypothalamic RvD2, which was accompanied by reduced body mass and improved glucose tolerance. The intracerebroventricular treatment with docosahexaenoic acid resulted in increased expression of the RvD2 synthetic enzymes, increased expression of anti-inflammatory cytokines and improved metabolic phenotype. Finally, intracerebroventricular treatment with RvD2 resulted in reduced adiposity, improved glucose tolerance and increased hypothalamic expression of anti-inflammatory cytokines.ConclusionsThus, RvD2 is produced in the hypothalamus, and its receptor and synthetic enzymes are modulated by dietary fats. The improved metabolic outcomes of RvD2 make this substance an attractive approach to treat obesity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0777-2) contains supplementary material, which is available to authorized users.