Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats.

OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n = 8), fructose (n = 8), and fructose+ simvastatin (n = 8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4 ± 0.32%/min) relative to that in the control group (4.4 ± 0.29%/min). Fructose + simvastatin rats exhibited increased insulin sensitivity (5.4 ± 0.66%/min). The fructose and fructose + simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124 ± 2 mmHg and fructose+simvastatin: 126 ± 3 mmHg vs. controls: 112 ± 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 ± 7 bpm) compared with that in the control (48 ± 7 bpm) and fructose+simvastatin groups (31 ± 8 bpm). The vagal effect was increased in fructose + simvastatin animals (84 ± 7 bpm) compared with that in control (49 ± 9 bpm) and fructose animals (46 ± 5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.

Effect of food restriction and intense physical training on estrous cyclicity and plasma leptin concentrations in rats.

Intense physical training and dietary energy restriction have been associated with consequences such as nutritional amenorrhea. We investigated the effects of intense physical training, food restriction or the combination of both strategies on estrous cyclicity in female rats, and the relationship between leptin ad these effects. Twenty-seven female Wistar rats were distributed into four groups: SF: sedentary, fed ad libitum; SR: sedentary subjected to 50% food restriction (based on the food intake of their fed counterparts); TF: trained (physical training on a motor treadmill with a gradual increase in speed and time), fed ad libitum; TR: trained with 50% food restriction. We analysed estrous cyclicity, plasma leptin and estradiol as well as chemical composition of the carcass, body weight variation, and weight of ovaries and perirenal adipose tissue. Data demonstrate that physical training alone was not responsible for significant modifications in either carcass chemical composition or reproductive function. Food restriction reduced leptin levels in all animals and interrupted the estrous cyclicity in some animals, but only the combination of food restriction and physical training was capable of interrupting the estrous cyclicity in all animals. Leptin was not directly related to estrous cyclicity. From our findings, it may be concluded that there is an additive or synergistic effect of energy intake restriction and energy expenditure by intense physical training on estrous cyclicity. Leptin appears to be one among others factors related to estrous cycle, but it probably acts indirectly.

Simvastatin-induced cardiac autonomic control improvement in fructose-fed female rats

OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8), fructose (n=8), and fructose+ simvastatin (n=8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32 percent/min) relative to that in the control group (4.4+ 0.29 percent/min). Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66 percent/min). The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 + 7 bpm) compared with that in the control (48 + 7 bpm) and fructose+simvastatin groups (31+8 bpm). The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm) compared with that in control (49 + 9 bpm) and fructose animals (46+5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.

Male and female odors induce Fos expression in chemically defined neuronal population.

Olfactory information modulates innate and social behaviors in rodents and other species. Studies have shown that the medial nucleus of the amygdala (MEA) and the ventral premammillary nucleus (PMV) are recruited by conspecific odor stimulation. However, the chemical identity of these neurons is not determined. We exposed sexually inexperienced male rats to female or male odors and assessed Fos immunoreactivity (Fos-ir) in neurons expressing NADPH diaphorase activity (NADPHd, a nitric oxide synthase), neuropeptide urocortin 3, or glutamic acid decarboxylase mRNA (GAD-67, a GABA-synthesizing enzyme) in the MEA and PMV. Male and female odors elicited Fos-ir in the MEA and PMV neurons, but the number of Fos-immunoreactive neurons was higher following female odor exposure, in both nuclei. We found no difference in odor induced Fos-ir in the MEA and PMV comparing fed and fasted animals. In the MEA, NADPHd neurons colocalized Fos-ir only in response to female odors. In addition, urocortin 3 neurons comprise a distinct population and they do not express Fos-ir after conspecific odor stimulation. We found that 80% of neurons activated by male odors coexpressed GAD-67 mRNA. Following female odor, 50% of Fos neurons coexpressed GAD-67 mRNA. The PMV expresses very little GAD-67, and virtually no colocalization with Fos was observed. We found intense NADPHd activity in PMV neurons, some of which coexpressed Fos-ir after exposure to both odors. The majority of the PMV neurons expressing NADPHd colocalized cocaine- and amphetamine-regulated transcript (CART). Our findings suggest that female and male odors engage distinct neuronal populations in the MEA, thereby inducing contextualized behavioral responses according to olfactory cues. In the PMV, NADPHd/CART neurons respond to male and female odors, suggesting a role in neuroendocrine regulation in response to olfactory cues.

[Leptin: aspects on energetic balance, physical exercise and athletic amenorhea]. / Leptina: aspectos sobre o balanço energético, exercício físico e amenorréia do esforço.

The aim of this manuscript was to review the knowledge about leptin, detailing its relationship with energetic intake and physical activity. Leptin is an adipocyte hormone, recognized mainly for its putative role in control of energy expenditure, food intake, body weight and reproductive function. Leptin has still important peripheral actions, including its role on the ovarian tissue. The intracellular signaling mechanisms are recognized in hypothalamus, but in peripheral tissue are not fully understood. The exercise, when practiced by women, if not appropriately planned according to food intake, can modify the leptin release. When energy imbalances induced by exercise and/or deficient food ingestion occurs, low leptin levels are observed, leading to a reduction in GnRH (gonadotropin-release hormone), in LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in pituitary, and consequently a minor release of ovarian estrogens. This process is named hypothalamic amenorrhea, and has repercussions in the woman's health. In this perspective, it is important to emphasize the need to evaluate the energy expenditure from exercise and to formulate adequate alimentary plans to these individuals.

Leptina: aspectos sobre o balanço energético, exercício físico e amenorréia do esforço / Leptin: aspects on energetic balance, physical exercise and athletic amenorhea

O presente manuscrito teve por objetivo realizar uma revisão bibliográfica acerca do papel da leptina no balanço energético, no exercício físico e na incidência da amenorréia do esforço. A leptina é um hormônio secretado pelo tecido adiposo, reconhecido principalmente por sua ação adipostática sobre o sistema nervoso central. Esse hormônio sinaliza o hipotálamo a respeito das reservas energéticas, modulando o funcionamento dos eixos hormonais que envolvam o hipotálamo e a hipófise. A leptina tem ainda ações periféricas importantes, incluindo seu papel sobre o tecido ovariano. Os mecanismos de sinalização intracelular desse hormônio foram identificados no hipotálamo, porém em tecidos periféricos há necessidade de maiores investigações. Existe certo consenso de que quando o exercício e a ingestão alimentar são capazes de promover um balanço energético negativo, as concentrações plasmáticas de leptina diminuem, alterando conseqüentemente: a liberação hipotalâmica de GnRH (fator hipotalâmico de liberação de gonadotrofinas); a liberação hipofisária de LH (hormônio luteinizante) e FSH (hormônio folículo-estimulante). Como resultado, há menor liberação de estrógenos ovarianos. Esse processo pode iniciar a chamada amenorréia hipotalâmica funcional, com repercussões na saúde da mulher. Nessa perspectiva, a avaliação do gasto energético e a elaboração de um plano alimentar adequado em atletas são fundamentais.

The aim of this manuscript was to review the knowledge about leptin, detailing its relationship with energetic intake and physical activity. Leptin is an adipocyte hormone, recognized mainly for its putative role in control of energy expenditure, food intake, body weight and reproductive function. Leptin has still important peripheral actions, including its role on the ovarian tissue. The intracellular signaling mechanisms are recognized in hypothalamus, but in peripheral tissue are not fully understood. The exercise, when practiced by women, if not appropriately planned according to food intake, can modify the leptin release. When energy imbalances induced by exercise and/or deficient food ingestion occurs, low leptin levels are observed, leading to a reduction in GnRH (gonadotropin-release hormone), in LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in pituitary, and consequently a minor release of ovarian estrogens. This process is named hypothalamic amenorrhea, and has repercussions in the woman's health. In this perspective, it is important to emphasize the need to evaluate the energy expenditure from exercise and to formulate adequate alimentary plans to these individuals.