Ginkgo biloba Extract (GbE) Stimulates the Hypothalamic Serotonergic System and Attenuates Obesity in Ovariectomized Rats

Menopause is associated with increased risk to develop obesity but the mechanisms involved are not fully understood. We have shown that Ginkgo biloba extract (GbE) improved diet-induced obesity. Since GbE might be effective in the treatment of obesity related to menopause, avoiding the side effects of hormone replacement therapy, we investigated the effect of GbE on hypothalamic systems controlling energy homeostasis. Wistar rats were either ovariectomized (OVX) or Sham-operated. After 2 months, either 500 mg.kg(-1) of GbE or vehicle were administered daily by gavage for 14 days. A subset of animals received an intracerebroventricular (i.c.v.) injection of serotonin (300 mu g) or vehicle and food intake was measured after 12 and 24 h. Another subset was submitted to in vivo microdialysis and 5-HT levels of the medial hypothalamus were measured by high performance liquid chromatography, before and up to 2 h after the administration of 500 mg.kg(-1) of GbE. Additional animals were used for quantification of 5-HT1A, 5-HT1B, 5-HT2C, 5-HTT, and pro-opiomelanocortin hypothalamic protein levels by Western blotting. OVX increased food intake and body weight and adiposity while GbE attenuated these alterations. i.c.v. serotonin significantly reduced food intake in Sham, Sham + GbE, and OVX + GbE groups while it failed to do so in the OVX group. In the OVX rats, GbE stimulated 5-HT microdialysate levels while it reduced hypothalamic 5-HTT protein levels. The results indicate that GbE improved the ovariectomy-induced resistance to serotonin hypophagia, at least in part through stimulation of the hypothalamic serotonergic activity. Since body weight gain is one of the most important consequences of menopause, the stimulation of the serotonergic transmission by GbE may represent a potential alternative therapy for menopause-related obesity.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Sao Paulo, Dept Fisiol, Disciplina Fisiol Nutr, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Setor Morfofisiol & Patol, Diadema, BrazilUniv Fed Sao Paulo, Dept Fisiol, Disciplina Fisiol Nutr, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Ciencias Biol, Setor Morfofisiol & Patol, Diadema, BrazilCNPq: 453924/2014-0FAPESP: 2012/03172-4FAPESP: 2014/18435-6Web of Scienc

Effect of fish oil intake on glucose levels in rat prefrontal cortex, as measured by microdialysis

Background: Brain glucose sensing may contribute to energy homeostasis control. the prefrontal cortex (PFC) participates in the hedonic component of feeding control. As high-fat diets may disrupt energy homeostasis, we evaluated in male Wistar rats whether intake of high-fat fish-oil diet modified cortical glucose extracellular levels and the feeding induced by intracerebroventricular glucose or PFC glucoprivation.Methods: Glucose levels in PFC microdialysates were measured before and after a 30-min meal. Food intake was measured in animals receiving intracerebroventricular glucose followed, 30-min. later, by 2-deoxy-D-glucose injected into the PFC.Results: the fish-oil group showed normal body weight and serum insulin while fat pads weight and glucose levels were increased. Baseline PFC glucose and 30-min. carbohydrates intake were similar between the groups. Feeding-induced PFC glucose levels increased earlier and more pronouncedly in fish-oil than in control rats. Intracerebroventricular glucose inhibited feeding consistently in the control but not in the fish-oil group. Local PFC glucoprivation with 2-DG attenuated glucose-induced hypophagia.Conclusions: the present experiments have shown that, following food intake, more glucose reached the prefrontal cortex of the rats fed the high-fat fish-oil diet than of the rats fed the control diet. However, when administered directly into the lateral cerebral ventricle, glucose was able to consistently inhibit feeding only in the control rats. the findings indicate that, an impairment of glucose transport into the brain does not contribute to the disturbances induced by the high-fat fish-oil feeding.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo Unifesp, Dept Fisiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo Unifesp, Dept Fisiol, BR-04023062 São Paulo, BrazilWeb of Scienc

Lateral hypothalamic serotonin is not stimulated during central leptin hypophagia

Whether leptin targets the hypothalamic serotonergic system to inhibit food intake is not established. We examined the effect of a short-term i.c.v. leptin treatment on serotonin microdialysate levels in rat lateral hypothalamus. Adipose tissue gene expression was also evaluated.Male rats received four daily injections of leptin (5 mu g) or vehicle (with pair-feeding to leptin-induced intake) and a fifth injection during collection of LH microdialysates. We found that serotonin and 5-HIAA levels were not affected by the leptin pre-treatment, as basal levels were similar between the leptin and the pair-fed group. These levels remained unaltered after the acute leptin injection.For gene expression studies, rats were pre-treated with five daily injections of either leptin (5 mu g) or vehicle (with either pair-feeding or ad libitum intake). mRNA levels of resistin, adiponectin, lipoprotein lipase, and PPAR-gamma were unaltered by either leptin or pair-feeding. Leptin gene expression was significantly reduced by leptin but not by pair-feeding, in both the retroperitoneal (- 74%) and the epididymal (- 99%) depots while no differences were observed in the subcutaneous depot.The observations confirmed the absence of an acute stimulatory effect of central leptin on serotonin release in the lateral hypothalamus and showed that the pre-treatment with leptin failed to modify this pattern. This indicates that components of the serotonergic system are probably not directly affected by leptin. Additionally, the central effect of leptin was able to downregulate its own adipose tissue gene expression in a depot-specific manner while other adipokine genes were not affected. (C) 2013 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, UNIFESP, Dept Fisiol, Disciplina Fisiol Nutr, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, Diadema, SP, BrazilUniversidade Federal de São Paulo, UNIFESP, Dept Fisiol, Disciplina Fisiol Nutr, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Ciencias Biol, Diadema, SP, BrazilWeb of Scienc

L-arginine abolishes the hypothalamic serotonergic activation induced by central interleukin-1 beta administration to normal rats

IL-1 beta-induced anorexia may depend on interactions of the cytokine with neuropeptides and neurotransmitters of the central nervous system control of energy balance and serotonin is likely to be one catabolic mediator targeted by IL-1 beta. in the complex interplay involved in feeding modulation, nitric oxide has been ascribed a stimulatory action, which could be of significance in counteracting IL-1 beta effects.The present study aims to explore the participation of the nitric oxide and the serotonin systems on the central mechanisms induced by IL-1 beta and the relevance of their putative interactions to IL-1 beta hypophagia in normal rats. Serotonin levels were determined in microdialysates of the ventromedial hypothalamus after a single intracerebroventricular injection of 10 ng of IL-1 beta, with or without the pre-injection of 20 mu g of the nitric oxide precursor L-arginine. IL-1 beta significantly stimulated hypothalamic serotonin extracellular levels, with a peak variation of 130 +/-37% above baseline. IL-1 beta also reduced the 4-h and the 24-h food intakes (by 23% and 58%, respectively). the IL-1 beta-induced serotonergic activation was abolished by the pre-injection of L-arginine while the hypophagic effect was unaffected.The data showed that one central effect of IL-1 beta is serotonergic stimulation in the ventromedial hypothalamus, an action inhibited by nitric oxide activity. It is suggested that, although serotonin participates in IL-1 beta anorexia, other mechanisms recruited by IL-1 beta in normal rats are able to override the absence of the serotonergic hypophagic influence.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Dept Physiol, BR-04023060 São Paulo, BrazilUniversidade Federal de São Paulo, Div Appl Stat, BR-04023060 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, BR-04023060 São Paulo, BrazilUniversidade Federal de São Paulo, Div Appl Stat, BR-04023060 São Paulo, BrazilWeb of Scienc

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.Universidade Federal de São Paulo (UNIFESP) Departamento de Ciências BiológicasUniversidade Federal de São Paulo (UNIFESP) Departamento de Fisiologia Disciplina de Fisiologia da NutriçãoUniversidade Federal de São Paulo (UNIFESP) Departamento de BiociênciasUniversidade Federal de Alagoas Faculdade de NutriçãoUniversidade Federal do Rio de Janeiro Curso de NutriçãoUNIFESP, Depto. de Ciências BiológicasUNIFESP, Depto. de Fisiologia Disciplina de Fisiologia da NutriçãoUNIFESP, Depto. de BiociênciasSciEL

Efeito da adrenalectomia e ingestão de sacarose sobre o metabolismo e comportamento alimentar em ratos normais e obesos pelo tratamento com Glutamato Monossódico

BV UNIFESP: Teses e dissertaçõe

Participation of adrenergic and cholinergic neurons as than as central and peripheric glycorecptors of feeding behavior and metabolic parameters of normal and obese rats - MSG

O presente trabalho teve por objetivo investigar em ratos normais (Controles) e obesos pelo tratamento neonatal com glutamato monossodico (MSG): 1 º - Se os glicoreceptores centrais eram sensiveis a glicoprivacao provocada pela injecao intracerebroventricular (icv) de 2 deoxi-D-glicose na dose de 10mG/10pL/5minutos. Nestas condicoes foi tambem avaliada a resposta reflexa da inGestão de alimentos, da concentracao plasmatica de glicose e da mobilizacao dos acidos graxos nao esterificados (NEFA). Os resultados mostraram que ratos MSG pesam menos e ingerem menor quantidade de alimentos entre 17 e 23 horas comparado aos ratos Controle. A injecao icv de 2 DG promoveu, nos ratos controle, aumento significativo do consumo alimentar (p<0,001)enquanto nos ratos MSG nao se observa resposta. Nos ratos Controle a injecao icv de 2 DG induziu aumento da concentracao plasmatica de glicose, enquanto nos ratos MSG em nenhum momento a glicemia diferiu do valor basal. A injecao icv de 2 DG promoveu aumento acentuado e progressivo da concentracao plasmatica de NEFA, nos ratos Controle. Os ratos MSG apresentaram valores basais de NEFA significativamente (p<0,001) mais elevados do que os Controle mas apos injecao icv de 2 DG nao houve resposta significativa. Podemos concluir que a falta de resposta reflexa do aumento da inGestão de alimentos, da glicemia e da mobilizacao de NEFA induzidos pela injecao icv de 2 DG, nos ratos MSG, e decorrente da lesao central provocada pela administracao neonatal de glutamato monossodico comprometendo a estimulacao dos glicoceptores envolvidos neste reflexo. 2º - Se tambem os glicoreceptores perifericos eram sensiveis a glicoprivacao . Para isto foi utilizada injecao intravenosa (i.v.) de 2 deoxi-D-glicose (2 DG) na dose de 1OOmG/Kg de peso corporeo e avaliada a resposta reflexa da inGestão de alimentos, da concentracao plasmatica de glicose e acidos graxos nao esterificados (NEFA). Os resultados mostraram que a injecao i.v. de 2 DG, em ambos grupos experimentais, nao promoveu inGestão de alimentos. Igualmente em ambos grupos ocorreu elevacao significativa (p<0,001) da glicemia sendo que nos ratos MSG esta...(au)BV UNIFESP: Teses e dissertaçõe

Monosodium glutamate (MSG)-obese rats develop glucose intolerance and insulin resistance to peripheral glucose uptake

Different levels of insulin sensitivity have been described in several animal models of obesity as well as in humans. Monosodium glutamate (MSG)-obese mice were considered not to be insulin resistant from data obtained in oral glucose tolerance tests. To reevaluate insulin resistance by the intravenous glucose tolerance test (IVGTT) and by the clamp technique, newborn male Wistar rats (N = 20) were injected 5 times, every other day, with 4 g/kg MSG (N = 10) or saline (control; N = 10) during the first 10 days of age, At 3 months, the IVGTT was performed by injecting glucose (0.75 g/kg) through the jugular vein into freely moving rats. During euglycemic clamping plasma insulin levels were increased by infusing 3 mU.kg(-1).min(-1) of regular insulin until a steady-state plateau was achieved. The basal blood glucose concentration did not differ between the two experimental groups, After the glucose load, increased values of glycemia (P<0.001) in MSG-obese rats occurred at minute 4 and from minute 16 to minute 32. These results indicate impaired glucose tolerance. Basal plasma insulin levels were 39.9 +/- 4 mu U/ml in control and 66.4 +/- 5.3 mu U/ml in MSG-obese rats. The mean post-glucose area increase of insulin was 111% higher in MSG-obese than in control rats. When insulinemia was clamped at 102 or 133 mu U/ml in control and MSG rats, respectively, the corresponding glucose infusion rate necessary to maintain euglycemia was 17.3 +/- 0.8 mg.kg(-1).min(-1) for control rats while 2.1 +/- 0.3 mg.kg(-1).min(-1) was sufficient for MSG-obese rats. The 2-h integrated area for total glucose metabolized, in mg.min.dl(-1), was 13.7 +/- 2.3 vs 3.3 +/- 0.5 for control and MSG rats, respectively. These data demonstrate that MSG-obese rats develop insulin resistance to peripheral glucose uptake.UNIV FED SAO PAULO,DEPT FISIOL,DISCIPLINA NEUROFISIOL & FISIOL ENDOCRINA,EPM,BR-04023900 SAO PAULO,SP,BRAZILUNIV FED SAO PAULO,DEPT FISIOL,DISCIPLINA NEUROFISIOL & FISIOL ENDOCRINA,EPM,BR-04023900 SAO PAULO,SP,BRAZILWeb of Scienc