Receptor-Mediated Transcytosis of Leptin through Human Intestinal Cells In Vitro

Gastric Leptin is absorbed by duodenal enterocytes and released on the basolateral side towards the bloodstream. We investigated in vitro some of the mechanisms of this transport. Caco-2/15 cells internalize leptin from the apical medium and release it through transcytosis in the basal medium in a time- temperature-dependent and saturable fashion. Leptin receptors are revealed on the apical brush-border membrane of the Caco-2 cells. RNA-mediated silencing of the receptor led to decreases in the uptake and basolateral release. Leptin in the basal medium was found bound to the soluble form of its receptor. An inhibitor of clathrin-dependent endocytosis (chlorpromazine) decreased leptin uptake. Confocal immunocytochemistry and the use of brefeldin A and okadaic acid revealed the passage of leptin through the Golgi apparatus. We propose that leptin transcytosis by intestinal cells depends on its receptor, on clathrin-coated vesicles and transits through the Golgi apparatus

Cranberry polyphenols and agave agavins impact gut immune response and microbiota composition while improving gut barrier function, inflammation, and glucose metabolism in mice fed an obesogenic diet

The consumption of plant-based bioactive compounds modulates the gut microbiota and interacts with the innate and adaptive immune responses associated with metabolic disorders. The present study aimed to evaluate the effect of cranberry polyphenols (CP), rich in flavonoids, and agavins (AG), a highly branched agave-derived neo-fructans, on cardiometabolic response, gut microbiota composition, metabolic endotoxemia, and mucosal immunomodulation of C57BL6 male mice fed an obesogenic high-fat and high-sucrose (HFHS) diet for 9 weeks. Interestingly, CP+AG-fed mice had improved glucose homeostasis. Oral supplementation with CP selectively and robustly (five-fold) increases the relative abundance of Akkermansia muciniphila, a beneficial bacteria associated with metabolic health. AG, either alone or combined with CP (CP+AG), mainly stimulated the glycan-degrading bacteria Muribaculum intestinale, Faecalibaculum rodentium, Bacteroides uniformis, and Bacteroides acidifaciens. This increase of glycan-degrading bacteria was consistent with a significantly increased level of butyrate in obese mice receiving AG, as compared to untreated counterparts. CP+AG-supplemented HFHS-fed mice had significantly lower levels of plasma LBP than HFHS-fed controls, suggesting blunted metabolic endotoxemia and improved intestinal barrier function. Gut microbiota and derived metabolites interact with the immunological factors to improve intestinal epithelium barrier function. Oral administration of CP and AG to obese mice contributed to dampen the pro-inflammatory immune response through different signaling pathways. CP and AG, alone or combined, increased toll-like receptor (TLR)-2 (Tlr2) expression, while decreasing the expression of interleukin 1ß (ILß1) in obese mice. Moreover, AG selectively promoted the anti-inflammatory marker Foxp3, while CP increased the expression of NOD-like receptor family pyrin domain containing 6 (Nlrp6) inflammasome. The intestinal immune system was also shaped by dietary factor recognition. Indeed, the combination of CP+AG significantly increased the expression of aryl hydrocarbon receptors (Ahr). Altogether, both CP and AG can shape gut microbiota composition and regulate key mucosal markers involved in the repair of epithelial barrier integrity, thereby attenuating obesity-associated gut dysbiosis and metabolic inflammation and improving glucose homeostasis

Circulating levels of linoleic acid and HDL-cholesterol are major determinants of 4-hydroxynonenal protein adducts in patients with heart failure

Objective: Measurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA). Methods and results: Circulating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R2=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only. Conclusion: Results from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts

Gabriel Tarde e as ciências sociais francesas: afinidades eletivas

Este artigo investiga os fatores que contribuíram para a ascensão intelectual de Tarde nos anos 1890, tendo-se em conta o fato de que o autor não tinha as credenciais acadêmicas necessárias para a carreira universitária. Procuro mostrar que Tarde conquistou prestígio junto a instâncias do poder intelectual e político contrárias à crescente autonomia da universidade e das ciências sociais. Os grupos pertencentes ao pólo pedagógico e ao pólo técnico-profissional ainda eram hegemônicos nos anos 1890, mas passaram a disputar com Durkheim a definição legítima das novas disciplinas. Como parte de uma estratégia estamental, esses grupos elegeram a psicologia social de Tarde como instrumento de combate, autor que correspondeu às expectativas e acumulou capital social nas mais diversas instâncias intelectuais e políticas, sendo por isso amplamente recompensado.<br>This article investigates the factors that contributed to the intellectual ascension of Tarde during the 1890's. Taking into account the fact that the author lacked the necessary academic credentials for a university career, I seek to show that Tarde obtained prestige among circles of intellectual and political power that were contrary to the growing autonomy of the university and the social sciences. Groups affiliated to the pedagogic pole and the technical-professional pole were still hegemonic in the 1890's, but they began to contend with Durkheim for the legitimate definition of the new disciplines. As part of a strategy of maintaining hierarchy, these groups elected the social psychology of Tarde as an instrument for combat. The author lived up to expectations and accumulated social capital in diverse intellectual and political fields, being thereby amply rewarded

Mágoas de amizade: um ensaio em antropologia das emoções

Neste ensaio, analiso a recorrência das categorias grosseria (rudeness) e ofensa (offence) no discurso sobre a amizade de um grupo de ingleses de camadas médias em Londres. Mais do que outros sentimentos ditos positivos, a menção freqüente a essas categorias aponta para uma tensão que atravessa o discurso sobre a amizade e que problematiza o espaço das amizades no conjunto mais amplo das relações sociais. Adoto, aqui, uma abordagem pragmática dentro do campo da "antropologia das emoções". Se, em um primeiro momento, os estudos priorizavam a relativização das categorias de emoções entre as culturas, verifica-se, mais recentemente, um movimento no sentido de tomar os discursos emotivos como práticas situadas em jogos de relações sociais e negociações de poder. Com isso, a emoção deixa de ser vista como experiência interna, subjetiva, para ser analisada como prática discursiva com efeitos externos, extrapolando o chamado domínio do privado.<br>In this essay, I discuss the presence of the categories rudeness and offence in the discourse on friendship produced by a group of middle class English people resident in London. The frequent reference to these categories, rather than to the so called positive emotions, reveals the tensions regarding the negotiation of personal space which crosscut this discourse, which in turn highlight the problematic space that friendship occupies within the field of social relations. This essay draws on the analytical tools of a pragmatic approach within the area known as "anthropology of emotions", developed in the last decade in the Unites States. If at first emotion concepts were mainly studied cross-culturally, nowadays they are seen as discursive practices situated within the wider field of social relations and negotiations of power. As such, emotions cease to be treated as an internal, purely subjective experience, in order to be analysed as a discursive practice with external effects on both private and public spheres