Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance.

CONTEXT Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. OBJECTIVE Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. DESIGN GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. RESULTS GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. CONCLUSIONS GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

Metabolomic insights into the intricate gut microbial-host interaction in the development of obesity and type 2 diabetes.

Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion, and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbial-host co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e., niacin), purines, and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbial-host crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders.

Política turística de Girona: 1976-2007

Es pretén fer una descripció de la política turística de la ciutat de Girona en el període 1976-2007. Es defineixen 6 objectius: estudiar el concepte de política turística, estudiar l’evolució del boom turístic dels 60 fins al turisme de qualitat dels 90, observar el repartiment de competències entre les diferents administracions, observar l’actual política turística de l’Ajuntament de Girona, descriure els fets que han influït en la política turística de la ciutat de Girona, i comparar la política turística estatal i la de Girona en aquest període

PPAR-mediated activity of phthalates: A link to the obesity epidemic?

The endocrine disruption hypothesis asserts that exposure to small amounts of some chemicals in the environment may interfere with the endocrine system and lead to harmful effects in wildlife and humans. Many of these chemicals may interact with members of the nuclear receptor superfamily. Peroxisome proliferator-activated receptors (PPARs) are such candidate members, which interact with many different endogenous and exogenous lipophilic compounds. More particularly, the roles of PPARs in lipid and carbohydrate metabolism raise the question of their activation by a sub-class of pollutants, tentatively named "metabolic disrupters". Phthalates are abundant environmental micro-pollutants in Europe and North America and may belong to this class. Mono-ethyl-hexyl-phthalate (MEHP), a metabolite of the widespread plasticizer di-ethyl-hexyl-phthalate (DEHP), has been found in exposed organisms and interacts with all three PPARs. A thorough analysis of its interactions with PPARgamma identified MEHP as a selective PPARgamma modulator, and thus a possible contributor to the obesity epidemic.

Association between obesity indices and cardiovascular risk factors in late adolescence in the Seychelles.

ABSTRACT: BACKGROUND: The ability of different obesity indices to predict cardiovascular risk is still debated in youth and few data are available in sub Saharan Africa. We compared the associations between several indices of obesity and cardiovascular risk factors (CVRFs) in late adolescence in the Seychelles. METHODS: We measured body mass index (BMI), waist circumference, waist/hip ratio (WHiR), waist/height ratio (WHtR) and percent fat mass (by bioimpedance) and 6 CVRFs (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting blood glucose and uric acid) in 423 youths aged 19-20 years from the general population. RESULTS: The prevalence of overweight/obesity and several CVRFs was high, with substantial sex differences. Except for glucose in males and LDL-cholesterol in females, all obesity indices were associated with CVRFs. BMI consistently predicted CVRFs at least as well as the other indices. Linear regression on BMI had standardized regression coefficients of 0.25-0.36 for most CVRFs (p<0.01) and ROC analysis had an AUC between 60%-75% for most CVRFs. BMI also predicted well various combinations of CVRFs: 36% of male and 16% of female lean subjects (BMI P90). CONCLUSION: There was an elevated prevalence of obesity and of several CVRFs in youths in Seychelles. BMI predicted single or combined CVRFs at least as well as other simple obesity indices.

Història urbana de Girona: el monar reial del Mercadal a Girona

De l'any 1015 consta l'existència del rec comtal, segons escriptura atorgada pel comte Ramon Borrell i per llur esposa, Ermessenda, que varen fer donació a la Seu de Santa Maria, el dia 19 de juny, de quatre mujades de terra situades prop del Mercadal iuxta urbem Gerundensis in ipso plano super ipsum Mercadalem. Les dites terres afrontaven de occiduo in ipso rege comitale i a migdia amb el riu Güell. Aquest fet permet considerar que el rec comtal feia possible, ja al segle XI, la instal·lació del Monar comtal amb llurs molins

Èmfasi contrareformista en els retaules de la seu de Girona

La catedral de Girona conserva un bon mostrari de retaules barrocs, ubicats en les capelles laterals de l'àmplia nau gòtica, fet que permet conèixer i detectar l'ambient artístic desenvolupat a la ciutat en el primer terç del segle XVIII. Entrant per la porta dels peus de la gran nau trobem, a banda i banda, els retaules de l'Anunciació i de la Immaculada Concepció; a la banda dreta, tot seguint la direcció vers l'altar, observem els retaules de sant Miquel i el dels sants Iu i Honorat; enfront, més a prop de la girola, s'hi troba el retaule de sant Narcís; i ja plenament en el deambulatori, el dels Dolors

The association of aldosterone with obesity-related hypertension and the metabolic syndrome.

Overweight and obesity are associated with arterial hypertension. Given the large increase in the obesity prevalence worldwide, the number of obese patients with hypertension is likely to increase substantially in the near future. Overweight and obese patients are exposed to an important metabolic and cardiovascular risk. The understanding of the mechanisms linking obesity to hypertension is important for specific prevention and therapy in this population. There is some evidence that obesity is associated with an increased aldosterone level. To date, 2 mechanisms may explain the interaction of fat tissue with the renin-angiotensin-aldosterone system, and therefore explain, in part, obesity-related hypertension. First, human adipose tissue produces several components of the renin-angiotensin-aldosterone system, mainly adipose tissue-derived angiotensinogen. Second, increased fatty acid production in the obese patient, especially nonesterified fatty acids, might stimulate aldosterone production, independent of renin. A better understanding of these mechanisms might have implications for the management of hypertension in overweight and obese patients. Because aldosterone also is associated with blood glucose and blood lipids, selective aldosterone blockade may represent a particularly attractive therapeutic strategy in obese patients with a clustering of cardiovascular risk factors.

Girona entre l'Islam i Carlemany: una ciutat de frontera (759-801)

Tradicionalment s'ha considerat l'ocupació de Girona pels francs (any 785) com el moment "fundacional" de la ciutat medieval, en paral·lel a la consideració que ha merescut l'època de Carlemany (final del segle VIII i principi del IX) com una època formativa en la història de Catalunya. Però tenim raons per pensar que aquells moments no significaren un gran terrabastall enuna ciutat que, des de començament del segle VIII, jugava un paper polític i militar significatiu en els esdeveniments de l'anomenada Marca Superior, el territori musulmà proper a les terres del regne franc. Més endavant, un cop incorporada a l'imperi carolingi, Girona mantingué la seva condició de ciutat capital de frontera o marca, fins a la conquesta de Barcelona l'any 801. Volem historiar, en la mesura del possible, aquesta etapa d'uns quaranta anys -entre 759 i 801- quan la ciutat visqué en primera línia i, també, protagonitzà les vicissituds de l'enfrontament entre dos dels grans estats d'aquell moment: la monarquia franca dels carolingis i l'emirat omeia A'al-Andalús. Els moviments d'anada i tomada dels seus exèrcits van situar Girona en primera línia de combat en aquells anys, fins a la definitiva consolidació del poder franc a principis del segle IX

El Camí de Sant Jaume en la provincia de Girona

En primer lugar se identifican las distintas rutas del Camí de Sant Jaume en la provincia de Girona con el objetivo de determinar cuáles han sido las principales rutas que los peregrinos han utilizado para su peregrinación hacia Santiago de Compostela dentro de la provincia de Girona. En segundo lugar se establecen los elementos que determinan que un itinerario concreto esté comprendido en el Camino de Santiago para lo cual se analizan las rutas y se buscan los componentes que tienen una relación directa con la peregrinación a Santiago de Compostela, bien por ser elementos descriptivos del Santo, bien por ser elementos que a lo largo de la historia se han atribuido a los peregrinos que peregrina a Santiago de Compostela. En tercer lugar se analiza el recorrido del Camí de Sant Jaume elegido por la Generalitat de Catalunya, se examinan los servicios que ofrece y las carencias o insuficiencias que posee. Finalmente se establece la confección de propuestas de mejora y las acciones pertinentes para corregir las debilidades que en su caso puedan tener estos itinerarios

Substrate metabolism, nutrient balance and obesity development in children and adolescents: a target for intervention?

Obesity results from the organism's inability to maintain energy balance over a long term. Childhood obesity and its related factors and pathological consequences tend to persist into adulthood. A cluster of factors, including high energy density in the diet (high fat intake), low energy expenditure, and disturbed substrate oxidation, favour the increase in fat mass. Oxidation of three major macronutrients and their roles in the regulation of energy balance, particularly in children and adolescents, are discussed. Total glucose oxidation is not different between obese and lean children; exogenous glucose utilization is higher whereas endogenous glucose utilization is lower in obese compared with lean children. Carbohydrate composition of the diet determines carbohydrate oxidation regardless of fat content of the diet. Both exogenous and endogenous fat oxidation are higher in obese than in lean subjects. The influence of high fat intake on accumulation of fat mass is operative rather over a long term. Several future directions are addressed, such that a combination of increased physical activity and modification in diet composition, in terms of energy density and glycemic index, is recommended for children and adolescents.

Projecte d'una passarel·la metàl·lica per a vianants amb tauler de fusta sobre el riu Onyar de Girona

Girona és famosa entre d’altres coses pels seus ponts sobre el riu Onyar.El nou pont que es vol projectar es vol situar entre el carrer del Carme i el carrer Emili Grahit de Girona al principi on la llera del riu Onyar comença a ser transitable. El projecte té com a objectiu la projecció (disseny, càlcul i construcció) d’unapassarel•la d’acer sobre el riu Onyar a Girona al seu començament de la zonatransitable a la llera del riu, que permeti el pas de vianants i vehicles rodats nomotoritzats, incloent cadires de rodes, bicicletes, carros de la compra i cotxets d’uncostat a l’altre del riu. Per aconseguir un disseny òptim sense necessitar d’utilitzar mésmaterial del necessari es decideix realitzar una passarel•la amb forma corba i un estudide la biga principal aplicant el mètode dels elements finits a través d’un programacomercial.L’abast del projecte és la de projectar una passarel•la metàl•lica de uns 50 metres dellarg i 4 metres d’amplada. Amb una estructura el mes apurada possible per tal de noutilitzar més material del compte i així poder abaratir costos. El material també ha deser un material bo i resistent a les inclemències meteorològiques per tal de tenir elmenor manteniment possible. A més ha de complir totes les normatives vigents deseguretat

La Desamortització a Girona: mite, realitat i anècdota

Article sobre la desamortització a les comarques gironines