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Acceso Abierto Oral Metformin Treatment Prevents Enhanced Insulin Demand and Placental Dysfunction in the Pregnant Rat Fed a Fructose-Rich Diet(Hindawi Publishing Corporation, 2012) Alzamendi, Ana; Del Zotto, Héctor; Castrogiovanni, Daniel; Romero, José; Giovambattista, Andrés; Spinedi, EduardoThe intake of a fructose-rich diet (FRD) in the normal female rat induces features similar to those observed in the human metabolic syndrome phenotype. We studied the impact of FRD administration to mothers on pregnancy outcome. On gestational day (Gd) zero rats were assigned to either group: ad libitum drinking tap water alone (normal diet, ND) or containing fructose (10% w/vol; FRD) through pregnancy; all rats were fed a Purina chow diet ad libitum ND and FRD rats were daily cotreated or not with metformin (60 mg/Kg/day oral; ND + MF and FRD + MF) and submitted to a high glucose load test on Gd 14. Additionally, placentas from different groups were studied on Gd 20. Data indicated that: (1) although FRD rats well tolerated glucose overload, their circulating levels of insulin were significantly higher than in ND rats; (2) the mesometrial triangle blood vessel area was significantly lower in placentas from FRD than ND dams; (3) the detrimental effects of FRD administration to mothers were ameliorated by metformin cotreatment. Our study suggests that excessive intake of fructose during pregnancy enhanced the risk for developing gestational diabetes and subsequent preeclampsia, and that metformin prevented the poor pregnancy outcome induced by FRD. - Artículo
Acceso Abierto Effect of Pioglitazone on the Fructose-Induced Abdominal Adipose Tissue Dysfunction(Hindawi Publishing Corporation, 2012) Alzamendi, Ana; Giovambattista, Andrés; Garcia, María Elisa; Rebolledo, Oscar R.; Gagliardino, Juan José; Spinedi, EduardoAim. To test the potential role of PPARγ in the endocrine abdominal tissue dysfunction induced by feeding normal rats with a fructose rich diet (FRD) during three weeks. Methodology. Adult normal male rats received a standard commercial diet (CD) or FRD, (10% in drinking water) without or with pioglitazone (PIO) (i.p. 0.25mg/Kg BW/day; CD-PIO and FRD-PIO). Thereafter, we measured circulating metabolic, endocrine, and oxidative stress (OS) markers, abdominal adipose tissue (AAT) mass, leptin (LEP) and plasminogen activator inhibitor-1 (PAI-1) tissue content/expression, and leptin release by isolated adipocytes incubated with different concentrations of insulin. Results. Plasma glucose, insulin, triglyceride, TBARS, LEP, and PAI-1 levels were higher in FRD rats; PIO coadministration fully prevented all these increments. AAT adipocytes from FRD rats were larger, secreted a higher amount of LEP, and displayed decreased sensitivity to insulin stimulation; these effects were significantly ameliorated by PIO. Whereas AAT LEP and PAI-1 (mRNA) concentrations increased significantly in FRD rats, those of insulin-receptor-substrate- (IRS-) 1 and IRS-2 were reduced. PIO coadministration prevented FRD effects on LEP, PAI-1, and IRS-2 (fully) and IRS-1 (partially) mRNAs in AAT. Conclusion. PPARγ would play a relevant role in the development of the FRD-induced metabolicendocrine dysfunction. - Artículo
Acceso Abierto Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats(2015) Castrogiovanni, Daniel; Ongaro, Luisina; Zuburía, Guillermina; Giovambattista, Andrés; Spinedi, EduardoRats neonatally treated withmonosodiumL-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly,metformin-treatedMSG rats corrected BWcatch-up and counteracted VAT (mass and leptinmRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformin therapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome. - Artículo
Acceso Abierto Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction(2016) Villagarcía, Hernán Gonzalo; Sabugo, Vanesa; Castro, María Cecilia; Schinella, Guillermo Raúl; Castrogiovanni, Daniel; Spinedi, Eduardo; Massa, María Laura; Francini, FlavioWe investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs)were increased. In conclusion adultMSGrats developed an insulinresistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis.These features, shared by both metabolic and Cushing’s syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation. - Artículo
Acceso Abierto High Risk of Metabolic and Adipose Tissue Dysfunctions in Adult Male Progeny, Due to Prenatal and Adulthood Malnutrition Induced by Fructose Rich Diet(2016) Alzamendi, Ana; Zubiría, Guillermina; Moreno, Gricelda; Portales, Andrea Estefanía; Spinedi, Eduardo; Giovambattista, AndrésThe aim of this work was to determine the effect of a fructose rich diet (FRD) consumed by the pregnant mother on the endocrine-metabolic and in vivo and in vitro adipose tissue (AT) functions of the male offspring in adulthood. At 60 days of age, rats born to FRD-fed mothers (F) showed impaired glucose tolerance after glucose overload and high circulating levels of leptin (LEP). Despite the diminished mass of retroperitoneal AT, this tissue was characterized by enhanced LEP gene expression, and hypertrophic adipocytes secreting in vitro larger amounts of LEP. Analyses of stromal vascular fraction composition by flow cytometry revealed a reduced number of adipocyte precursor cells. Additionally, 60 day-old control (C) and F male rats were subjected to control diet (CC and FC animals) or FRD (CF and FF rats) for three weeks. FF animals were heavier and consumed more calories. Their metabolic-endocrine parameters were aggravated; they developed severe hyperglycemia, hypertriglyceridemia, hyperleptinemia and augmented AT mass with hypertrophic adipocytes. Our study highlights that manipulation of maternal diet induced an offspring phenotype mainly imprinted with a severely unhealthy adipogenic process with undesirable endocrine-metabolic consequences, putting them at high risk for developing a diabetic state. - Artículo
Acceso Abierto Long-Term Fructose Intake Increases Adipogenic Potential: Evidence of Direct Effects of Fructose on Adipocyte Precursor Cells(2016) Zubiría, Guillermina; Alzamendi, Ana; Moreno, Griselda; Rey, María Amanda; Spinedi, Eduardo; Giovambattista, AndrésWe have previously addressed that fructose rich diet (FRD) intake for three weeks increases the adipogenic potential of stromal vascular fraction cells from the retroperitoneal adipose tissue (RPAT). We have now evaluated the effect of prolonged FRD intake (eight weeks) on metabolic parameters, number of adipocyte precursor cells (APCs) and in vitro adipogenic potential from control (CTR) and FRD adult male rats. Additionally, we have examined the direct fructose effects on the adipogenic capacity of normal APCs. FRD fed rats had increased plasma levels of insulin, triglyceride and leptin, and RPAT mass and adipocyte size. FACS studies showed higher APCs number and adipogenic potential in FRD RPAT pads; data is supported by high mRNA levels of competency markers: PPARγ2 and Zfp423. Complementary in vitro experiments indicate that fructose-exposed normal APCs displayed an overall increased adipogenic capacity. We conclude that the RPAT mass expansion observed in eight week-FRD fed rats depends on combined accelerated adipogenesis and adipocyte hypertrophy, partially due to a direct effect of fructose on APCs. - Artículo
Acceso Abierto Relationship between the Balance of Hypertrophic/Hyperplastic Adipose Tissue Expansion and the Metabolic Profile in a High Glucocorticoids Model(2016) Zubiría, Guillermina; Alzamendi, Ana; Moreno, Griselda; Portales, Andrea Estefanía; Castrogiovanni, Daniel; Spinedi, Eduardo; Giovambattista, AndrésAdipose tissue (AT) expansion is the result of two processes: hyperplasia and hypertrophy; and both, directly or indirectly, depend on the adipogenic potential of adipocyte precursor cells (APCs). Glucocorticoids (GCs) have a potent stimulatory effect on terminal adipogenesis; while their effects on early stages of adipogenesis are largely unknown. In the present work, we study, in a model of high GC levels, the adipogenic potential of APCs from retroperitoneal AT (RPAT) and its relationship with RPAT mass expansion. We employed a model of hyper-adiposity (30- and 60-day-old rats) due to high endogenous GC levels induced by neonatal treatment with L-monosodium glutamate (MSG).We found that the RPAT APCs from 30-day-old MSG rats showed an increased adipogenic capacity, depending on the APCs’ competency, but not in their number. Analyses of RPAT adipocyte diameter revealed an increase in cell size, regardless of the rat age, indicating the prevalence of a hypertrophic process. Moreover, functional RPAT alterations worsened in 60-day-old rats, suggesting that the hyperplastic AT expansion found in 30-day-old animals might have a protective role. We conclude that GCs chronic excess affects APCs’ adipogenic capacity, modifying their competency. This change would modulate the hyperplastic/hypertrophic balance determining healthy or unhealthy RPAT expansion and, therefore, its functionality. - Artículo
Acceso Abierto Prevención primaria de diabetes tipo 2 en Argentina: estudio piloto en la provincia de Buenos Aires(Sociedad Argentina de Endocrinología y Metabolismo (SAEM); Federación Argentina de Sociedades de Endocrinología (FASEN), 2016) Gagliardino, Juan José; Etchegoyen, Graciela; Bourgeois, Marcelo; Fantuzzi, Gabriel; García, Silvia; González, Lorena; Elgart, Jorge Federico; Ré, Matías; Ricart, Alberto; Ricart, Juan Pablo; Spinedi, EduardoIntervenciones: Sobre estilo de vida, previenen el desarrollo de diabetes tipo 2 (DMT2) en personas con tolerancia a la glucosa o glucemia de ayunas alterada (TGA y GAA, respectivamente), aisladas o combinadas. Objetivo: Evaluar la efectividad de adoptar estilo de vida saludable sobre la manifestación clínica de DMT2 en personas con riesgo de desarrollarla. Metodología: Estudio prospectivo en participantes de 3 municipios de provincia de Buenos Aires (La Plata, Berisso y Ensenada), mediante cuestionario FINDRISC; quienes superen su puntaje de riesgo (≥ 13), realizarán prueba de tolerancia oral a la glucosa. El estudio incluirá a todas las personas con TGA/GAA que deseen participar y firmen un consentimiento informado, distribuidas en 2 grupos: a) intervención autoadministrada, y b) intervención intensificada (talleres de modalidad grupal mensuales sobre plan de alimentación saludable y práctica regular de actividad física 3 veces por semana). Ambos grupos tendrán un seguimiento de 2 an˜ os. Se utilizarán cuestionarios para evaluar bienestar, hábitos alimentarios y actividad física de cada participante al inicio del estudio y cada 6 meses durante el seguimiento. En ambos grupos se realizarán individualmente mediciones antropométricas y análisis de laboratorio a los 0, 12 y 24 meses. Igualmente, se evaluará la coste-efectividad de las estrategias implementadas. Resultados y conclusiones: Los resultados del estudio permitirán: a) demostrar la factibilidad y el costo de este tipo de programas: b) identificar genotipos de personas en riesgo facilitando intervenir en ellas precoz y eficientemente; c) definir si estas intervenciones también mejoran otros FRCV presentes; d) cuantificar las lesiones de microangiopatía (microaneurismas retinianos) en población con TGA/GAA, y e) identificar barreras y alianzas estratégicas interdisciplinarias e intersectoriales para la implementación efectiva de este tipo de programas. - Artículo
Acceso Abierto VMP1- Related autophagy induced by fructose rich diet in β-cells: its prevention by incretins(2017) Maiztegui, Bárbara; Boggio, Verónica; Román, Carolina Lisi; Flores, Luis Emilio; Del Zotto, Héctor; Ropolo, Alejandro; Grasso, Daniel; Vaccaro, María I.; Gagliardino, Juan JoséTo demonstrate the role of autophagy and incretins on fructose‐induced alteration in β‐cell mass and function. Methods: Normal Wistar rats were fed (3 weeks) with commercial diet without (C) or with 10% fructose in drinking water (F) alone or plus sitagliptin (CS and FS) or exendin‐4 (CE and FE). Serum levels of metabolic/endocrine parameters, β‐cell mass, morphology/ultrastructure and apoptosis, VMP1 expression and glucose‐stimulated insulin secretion (GSIS) were studied. Complementary, islets isolated from normal rats were cultured (3 days) without (C) or with F and F plus exendin‐4 (FE) or chloroquine (FCQ). Expression of autophagy related‐proteins (VMP1 and LC3), apoptotic/antiapoptotic markers (caspase‐3 and Bcl‐2), GSIS and insulin mRNA levels were measured. Results: F rats developed impaired glucose tolerance (IGT) and a significant increase in plasma triglyceride, TBARS, insulin levels, HOMAIR and HOMA‐β indexes. Significant β‐cell mass reduction was associated to an increased apoptotic rate and morphological/ultrastructural changes indicative of autophagic activity. All these changes were prevented by either sitagliptin or exendin‐4. In cultured islets, F significantly enhanced insulin mRNA and GSIS, decreased Bcl‐2 mRNA levels and increased caspase‐3 expression. Chloroquine reduced these changes suggesting autophagy participation in this process. Indeed, F induced the increase of both, VMP1 expression and LC3‐II, suggesting that VMP1‐related autophagy is activated in injured β‐cell. Exendin‐4 prevented islet‐cell damage and autophagy development. Conclusions: VMP1‐related autophagy is a reactive process against Finduced islet dysfunction, being prevented by exendin‐4 treatment. This knowledge could help to use autophagy as potential target for preventing progression from IGT toT2DM. - Comunicacion
Acceso Abierto Estudio exploratorio de la oferta de bebidas sin alcohol en comercios mayoristas y minoristas de ciudad de La Plata(2017) Papalardo, Brenda; García, Silvia; Prestes, Mariana; Fasano, María Victoria; Olmedo, Luciana; Henning, María Florencia; Malpeli, Agustina; Bisceglia, María Gabriela; Pellon Maison, MagaliLos hábitos de consumo alimentario actuales promueven el sobrepeso y la obesidad. Se consiguen alimentos a menores precios, particularmente aquellos con una alta densidad energética y con mayor grado de procesamiento, como las bebidas endulzadas con edulcorantes calóricos. La Argentina se posiciona como uno de los líderes del mercado y como uno de los mayores consumidores a nivel mundial de este tipo de bebidas. Los objetivos de este trabajo fueron: -Explorar el contenido total de hidratos de carbono y tipo de edulcorante de las bebidas sin alcohol ofrecidas a la venta en comercios de La Plata. -Comparar la oferta de bebidas sin alcohol y su contenido en edulcorantes calóricos y no calóricos en comercios de centros comunales de diferente nivel socioeconómico.