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

Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression

Sleep deprivation in humans has been related to weight gain and consequently, increased risk for insulin resistance. In contrast, there is a significant loss of weight in sleep deprived rats suggesting a state of insulin resistance without obesity interference. Thus, we aimed to assess the effects of a rich fish oil dietetic intervention on glucose tolerance, serum insulin and adiponectin, and adipose tissue gene expression of adiponectin and TNF-α of paradoxically sleep deprived (PSD) rats. The study was performed in thirty day-old male Wistar randomly assigned into two groups: rats fed with control diet (soybean oil as source of fat) and rats fed with a fish oil rich diet. After 45 days of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h. Body weight and food intake were carefully monitored in all groups. At the end of PSD period, a glucose tolerance test was performed and the total blood and adipose tissues were collected. Serum insulin and adiponectin were analyzed. Adipose tissues were used for RT-PCR to estimate the gene expression of adiponectin and TNF-α. Results showed that although fish oil diet did not exert any effect upon these measurements, PSD induced a reduction in adiponectin gene expression of retroperitoneal adipose tissues, with no change in serum adiponectin concentration or in adiponectin and TNF-α gene expression of epididymal adipose tissue. Thus, the stress induced by sleep deprivation lead to a desbalance of adiponectin gene expression

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

Impact of insomnia on pain in postmenopausal women

Background: Sleep disturbances and pain are assumed to be reciprocally linked. Insomnia and pain are central symptoms of the postmenopausal period and are closely related. Insomnia affects quality of life, increases pain sensitivity, the risk of pain-related disability, and other health problems.Objective: To investigate whether insomnia influences aspects of pain (pain intensity and the effect of pain on daily function) in postmenopausal women, and to evaluate the objective sleep pattern of insomniacs with pain.Methods: Fifty-seven women completed questionnaires about insomnia, climacteric symptoms, and pain. Polysomnography data were collected as well as their medical history. Patients were allocated into three groups: control, subthreshold insomnia, and insomnia. Pain intensity, climacteric symptoms and objective sleep pattern were compared between groups.Results: Postmenopausal women with insomnia had statistically significant higher pain interference in their activities (e.g. relationships with other people, enjoyment of life and sleep) than controls, and had more severe climacteric symptoms. There were no statistically significant differences in pain intensity and objective sleep pattern between groups.Conclusions: Insomnia status affected climacteric symptoms and pain interference, but not pain intensity in postmenopausal women. Women with insomnia had higher rates of climacteric symptoms than those without insomnia or those with subthreshold insomnia. No changes in objective sleep pattern were found.Associação Fundo de Incentivo à Psicofarmacologia (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Nutr, Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Gynecol, Sao Paulo, BrazilUniversidade Federal de São Paulo (UNIFESP), Dept Psychobiol, Sao Paulo, BrazilUniversidade Federal de São Paulo (UNIFESP), Dept Nutr, Sao Paulo, BrazilUniversidade Federal de São Paulo (UNIFESP), Dept Gynecol, Sao Paulo, BrazilFAPESP: 2014/18722-5CNPq: 158506/2014-6Web of Scienc