Prevention of metabolic disorders and reproductive performance deficits by the blockade of Angiotensin II AT1 receptor in female rats fed with cafeteria diet

Sagae, Sara Cristina; Lubaczeuski, Camila; Zacharias, Patricia; Bonfleur, Maria Lúcia; Franci, Celso Rodrigues; Sanvitto, Gilberto Luiz

doi:10.1016/j.physbeh.2013.05.029

Cited by 10 publications

(10 citation statements)

References 56 publications

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“…In line with previous findings (Machado et al, 2012; Sagae et al, 2013; Oliveira-Junior et al, 2014), we show that oral administration of losartan abolishes weight gain in DIO rats fed a HFD without influencing body weight in age-matched chow fed, animals. Our study, however, extends these findings to show that AT1R receptor blockade also prevents weight gain in animals fed a HFD but who were not obese (DR animals).…”

Section: Discussionsupporting

confidence: 93%

“…Blockade of AT1R by a variety of pharmacological agents have also been shown to prevent HFD induced body weight gain (Sharieh Hosseini et al, 2014) or to impair body weight gain in DIO animals (Machado et al, 2012; Miesel et al, 2012; Sagae et al, 2013; Oliveira-Junior et al, 2014). An interesting finding of the present study is that AT1R blockade had a similar effect on weight gain in the DR animals but not in age-matched chow fed controls suggesting a role for the RAS on body weight gain only in animals receiving a HFD regardless of body weight and adiposity.…”

Section: Discussionmentioning

confidence: 99%

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AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

et al. 2014

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Obesity is a chronic metabolic condition with important public health implications associated with numerous co-morbidities including cardiovascular disease, insulin resistance, and hypertension. The renin angiotensin system (RAS), best known for its involvement in cardiovascular control and body fluid homeostasis has, more recently, been implicated in regulation of energy balance. Interference with the RAS (genetically or pharmacologically) has been shown to influence body weight gain. In this study we investigated the effects of systemic AT1 receptor blockade using losartan on ingestive behaviors and weight gain in diet induced obese (DIO) rats. Prior to losartan administration (30 mg/kg/day) body weight gain remained constant within the DIO animals (3.6 ± 0.3 g/day, n = 8), diet resistant (DR) animals (2.1 ± 0.6 g/day, n = 8) and in the age-matched chow fed control (CHOW) animals (2.8 ± 0.3 g/day, n = 8), Losartan administration abolished body weight gain in animals fed a high fat diet (DIO: -0.4 ± 0.7 g/day, n = 8; and DR: -0.8 ± 0.3 g/day, n = 8) while chow fed animals continued to gain weight (2.2 ± 0.3 g/day, n = 8) as they had previously to oral administration of losartan. This decrease in daily body weight gain was accompanied by a decrease in food intake in the HFD fed animals. Following the removal of losartan, both the DIO and DR animals again showed daily increases in body weight gain and food intake which were similar to control values. Our data demonstrate that oral losartan administration attenuates body weight gain in animals fed a HFD whether the animal is obese (DIO) or not DR while having no effect on body weight gain in age-matched chow fed animals suggesting a protective effect of losartan against body weight gain while on a HFD.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

et al. 2014

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“…E2 and P4 exert both (1) rapid effects (on the order of hours) due to ovarian steroids and their metabolites acting as neuromodulators in the central nervous system (McEwen, 2002) and (2) lagged effects on the order of days due to E2 and P4 acting as traditional steroids (Bless et al, 1997; Schiller et al, 2013). In order to capture these influences of E2 and P4, we chose to use the average scores for each of these six outcomes across the three days following (days ±1, ±2, and ±3) each blood sample (day 0).…”

Section: Methodsmentioning

confidence: 99%

Histories of abuse predict stronger within-person covariation of ovarian steroids and mood symptoms in women with menstrually related mood disorder

Eisenlohr‐Moul

Rubinow

Schiller

et al. 2016

Psychoneuroendocrinology

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Objective Individual differences in sensitivity to cyclical changes in ovarian steroids estradiol (E2) and progesterone (P4) have been implicated in the pathophysiology of menstrually related mood disorder (MRMD). However, no prospective studies have investigated psychosocial risk factors for sensitivity to hormone effects on mood in MRMD. Using a repeated measures approach and multilevel models, we tested the hypothesis that a history of abuse provides a context in which within-person elevations of E2 and P4 prospectively predict daily symptoms. Method 66 women with prospectively-confirmed MRMD recruited for a trial of oral contraceptives provided 1 month of baseline hormone and mood data prior to randomization. Lifetime physical and sexual abuse experiences were assessed. Across one cycle, women completed daily measures of symptoms and provided blood samples on 5 days across the menstrual cycle. Current E2 and P4 were centered within person (CWP) such that higher values represented cyclical elevations in hormones. Results Rates of physical (27%) and sexual (29%) abuse were high, consistent with previous work documenting a link between trauma and MRMD. In women with a history of physical abuse, cyclical increases in P4 predicted greater mood and interpersonal symptoms on the three days following that sample. In women with a history of sexual abuse, cyclical increases in E2 predicted greater anxiety symptoms on the three days following that sample. Conclusions Results inform further inquiry into the role of severe life stressors and stress response systems in MRMD. We discuss areas for future research on the psychosocial and physiological pathways through which abuse may influence the link between hormones and symptoms.

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“…No entanto, ainda não está claro se esse efeito é direto sobre os parâmetros reprodutivos, ou indireto, por meio do restabelecimento dos parâmetros metabólicos. Vias endócrinas, inflamatórias, neurais e celular-intrínsecas estão desreguladas na obesidade e evidências sugerem que o SRA pode estar envolvido nos problemas associados com a obesidade 7 . Considerando que os efeitos benéficos do LOS sobre a ovulação estão associados ao papel protetor contra o acúmulo de gordura, à resistência à insulina e ao aumento das concentrações plasmáticas de triglicérides e LDL 8 , a utilização de fármacos inibidores do SRA que melhoram a síndrome metabólica 14 poderia favorecer indiretamente a fertilidade na obesidade.…”

Section: Discussionunclassified

“…A atividade do sistema renina-angiotensina (SRA) está aumentada na obesidade 7 e pode ter efeito mediador nas alterações reprodutivas relacionadas com essa doença 5 . O bloqueio do receptor AT 1 da Angiotensina II, desde o desmame, em fêmeas de roedores alimentadas por DCAF previne a hipertrofia do tecido adiposo, melhora a sensibilidade à insulina, restabelece o pico pré-ovulatório de LH e a ovulação, além de melhorar o perfil reprodutivo das ratas 8 .…”

Section: Introductionunclassified

Bloqueio do receptor AT1 da Angiotensina II reduz o número de folículos antrais em ratas com obesidade induzida por dieta de cafeteria

Sagae¹,

Gobo²,

Paz³

et al. 2015

Rev. Bras. Ginecol. Obstet.

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ResumoOBJETIVO: Avaliar o desenvolvimento folicular em ratas Wistar com obesidade induzida por dieta de cafeteria (DCAF) submetidas à administração de losartan (LOS), um antagonista do receptor AT 1 da Angiotensina II. MÉTODOS: Aos 21 dias de vida, as ratas foram separadas aleatoriamente em dois grupos: controle (CTL), que recebeu ração padrão, e cafeteria (CAF), que recebeu a DCAF, altamente palatável e calórica. Aos 70 dias de vida, início da idade reprodutiva, animais do grupo CAF foram subdivididos em dois grupos (n=15/grupo): CAF, que recebeu água, e CAF+LOS, que recebeu 30 mg/kg de peso corporal (PC) de LOS por gavagem durante 30 dias. O grupo CTL também recebeu água por gavagem. Aos 100 dias de vida foi realizada a eutanásia dos animais e o PC e das gorduras retroperitoneal, perigonadal e subcutânea foi avaliado. Os ovários direitos foram retirados para contagem do número dos diferentes tipos de folículos ovarianos. As concentrações plasmáticas dos hormônios folículo-estimulantes (FSH), luteinizante (LH), prolactina (PRL) e progesterona foram avaliadas. Os resultados foram expressos como média±erro padrão da média. Para análise estatística, foi utilizado one-way ANOVA, seguido pelo pós-teste de Newman-Keuls (p<0,05). RESULTADOS: O PC e das gorduras, assim como o número de folículos antrais, foi elevado no grupo CAF em relação ao CTL. Todavia, as concentrações de FSH e LH foram mais baixas entre os animais CAF. A administração de LOS reduziu o PC e das gorduras retroperitoneal e subcutânea, bem como o número de folículos antrais. O tratamento com LOS atenuou a redução das concentrações de FSH e de LH. As concentrações de progesterona e PRL foram semelhantes entre os grupos estudados. CONCLUSÃO: O uso de LOS pode favorecer o desenvolvimento folicular em fêmeas obesas e pode possibilitar sua utilização como fármaco coadjuvante no tratamento da infertilidade associada à obesidade. Abstract PURPOSE:To evaluate the follicular development of female Wistar rats with obesity induced by the cafeteria diet, submitted to the administration of losartan (LOS), an antagonist of the AT 1 receptor of Angiotensin II. METHODS: At weaning (21 days of age), female Wistar rats were randomly divided, into two groups: control (CTL) that received standard chow and cafeteria (CAF) that received a cafeteria diet, a highly palatable and highly caloric diet. At 70 days of age, at the beginning of the reproductive age, animals of the CAF group were subdivided into two groups (n=15/ group): CAF, that received water, and CAF+LOS, that received LOS for 30 days. The CTL group also received water by gavage. At 100 days of age, the animals were euthanized and body weight (BW) as well as the retroperitoneal, perigonadal and subcutaneous fat weights were analyzed. The right ovaries were isolated for counting the number of primary, secondary, antral and mature follicles. Plasma levels of FSH, LH, prolactin and progesterone hormones were analyzed. The results were expressed as mean±standard error of the mean. Data were analyzed statistically by...

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Prevention of metabolic disorders and reproductive performance deficits by the blockade of Angiotensin II AT1 receptor in female rats fed with cafeteria diet

Cited by 10 publications

References 56 publications

AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

Histories of abuse predict stronger within-person covariation of ovarian steroids and mood symptoms in women with menstrually related mood disorder

Bloqueio do receptor AT1 da Angiotensina II reduz o número de folículos antrais em ratas com obesidade induzida por dieta de cafeteria

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Prevention of metabolic disorders and reproductive performance deficits by the blockade of Angiotensin II AT1 receptor in female rats fed with cafeteria diet

Cited by 10 publications

References 56 publications

AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

Histories of abuse predict stronger within-person covariation of ovarian steroids and mood symptoms in women with menstrually related mood disorder

Bloqueio do receptor AT1 da Angiotensina II reduz o n&#250;mero de fol&#237;culos antrais em ratas com obesidade induzida por dieta de cafeteria

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Bloqueio do receptor AT1 da Angiotensina II reduz o número de folículos antrais em ratas com obesidade induzida por dieta de cafeteria