RESUMO
The aim of this study was to investigate the effect of calorie restriction (CR) during pregnancy in mice on metabolism and ovarian function in the offspring. Pregnant female mice were divided into two groups, a control group and a CR group (n=7 in each). Mice in the CR group were fed 50% of the amount consumed by control females from Day 10 of gestation until delivery. After weaning, the offspring received diet ad libitum until 3 months of age, when ovaries were collected. Ovaries were serially cut and every sixth section was used for follicle counting. Female offspring from CR dams tended to have increased bodyweight compared with offspring from control females (P=0.08). Interestingly, fewer primordial follicles (60% reduction; P=0.001), transitional follicles (P=0.0006) and total follicles (P=0.006) were observed in offspring from CR mothers. The number of primary, secondary and tertiary follicles did not differ between the groups (P>0.05). The CR offspring had fewer DNA double-strand breaks in primary follicle oocytes (P=0.03). In summary, CR during the second half of gestation decreased primordial ovarian follicle reserve in female offspring. These findings suggest that undernutrition during the second half of gestation may decrease the reproductive lifespan of female offspring.
Assuntos
Restrição Calórica/efeitos adversos , Reserva Ovariana/fisiologia , Fenômenos Fisiológicos da Nutrição Pré-Natal/fisiologia , Animais , Animais Recém-Nascidos , Feminino , Glucose/metabolismo , Masculino , Desnutrição/complicações , Desnutrição/metabolismo , Desnutrição/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Reprodução/fisiologiaRESUMO
Nutritional disorders during the perinatal period cause cardiometabolic dysfunction, which is observable in the early overfeeding (EO) experimental model. Therefore, severe caloric restriction has the potential of affecting homeostasis through the same epigenetic mechanisms, and its effects need elucidation. This work aims to determine the impact of food restriction (FR) during puberty in early overfed obese and non-obese animals in adult life. Three days after delivery (PN3), Wistar rats were separated into two groups: normal litter (NL; 9 pups) and small litter (SL; 3 pups). At PN30, some offspring were subjected to FR (50%) until PN60, or maintained with free access to standard chow. NL and SL animals submitted to food restriction (NLFR and SLFR groups) were kept in recovery with free access to standard chow from PN60 until PN120. Body weight and food intake were monitored throughout the experimental period. At PN120 cardiovascular parameters were analyzed and the animals were euthanized for sample collection. SLNF and SLFR offspring were overweight and had increased adiposity. Differences in blood pressure were observed only between obese and non-obese animals. Obese and FR animals have cardiac remodeling showing cardiomyocyte hypertrophy and the presence of interstitial and perivascular fibrosis. FR animals also show increased expression of AT1 and AT2 receptors and of total ERK and p-ERK. The present study showed that EO leads to the obese phenotype and cardiovascular disruptions. Interestingly, we demonstrated that severe FR during puberty leads to cardiac remodeling.
Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente/fisiologia , Desnutrição/complicações , Obesidade/fisiopatologia , Hipernutrição/complicações , Remodelação Ventricular/fisiologia , Animais , Animais Recém-Nascidos , Peso Corporal , Restrição Calórica/efeitos adversos , Modelos Animais de Doenças , Feminino , Ventrículos do Coração/crescimento & desenvolvimento , Humanos , Lactente , Recém-Nascido , Masculino , Desnutrição/diagnóstico , Desnutrição/fisiopatologia , Obesidade/etiologia , Hipernutrição/fisiopatologia , Ratos , Ratos Wistar , Índice de Gravidade de DoençaRESUMO
According to the developmental origins of health and disease (DOHaD) hypothesis, changes in the maternal environment are known to reprogram the metabolic response of offspring. Known for its redox modulation, caloric restriction extends the lifespan of some species, which contributes to diminished cellular damage. Little is known about the effects of gestational caloric restriction, in terms of antioxidant parameters and molecular mechanisms of action, on the reproductive organs of offspring. This study assessed the effects of moderate (20%) caloric restriction on redox status parameters, molecular expression of sirtuin (SIRT) 1 and SIRT3 and histopathological markers in the ovaries and testes of adult rats that were subjected to gestational caloric restriction. Although enzyme activity was increased, ovaries from female pups contained high levels of oxidants, whereas testes from male pups had decreased antioxidant enzyme defences, as evidenced by diminished glyoxalase I activity and reduced glutathione content. Expression of SIRT3, a deacetylase enzyme related to cellular bioenergetics, was increased in both ovaries and testes. Previous studies have suggested that, in ovaries, diminished antioxidant metabolism can lead to premature ovarian failure. Unfortunately, there is little information regarding the redox profile in the testis. This study is the first to assess the redox network in both ovaries and testes, suggesting that, although intrauterine caloric restriction improves molecular mechanisms, it has a negative effect on the antioxidant network and redox status of reproductive organs of young adult rats.
Assuntos
Restrição Calórica/efeitos adversos , Mitocôndrias/metabolismo , Ovário/metabolismo , Efeitos Tardios da Exposição Pré-Natal , Sirtuínas/análise , Testículo/metabolismo , Animais , Antioxidantes/análise , Antioxidantes/metabolismo , Feminino , Masculino , Ovário/química , Oxirredução , Gravidez , Ratos , Ratos Wistar , Sirtuína 1/análise , Sirtuína 3/análise , Testículo/químicaRESUMO
OBJECTIVE: We aim to evaluate the effect of caloric restriction (CR) in cognition by comparing performance in neuropsychological tests for working memory between a group of non-obese healthy subjects doing CR for 2 years with another consuming ad libitum diet (AL). METHODS: This study was part of a larger multicenter trial called CALERIE that consisted of a randomized clinical trial with parallel-group comparing 2 years of 25% CR and AL in 220 volunteers with a BMI between 22 and 28 kg/m2, across 3 sites. The cognitive tests used were the Cambridge Neuropsychological Tests Automated Battery (CANTAB) for Spatial Working Memory (SWM) including the total number of errors (SWMTE) and strategy (SWMS). Included as possible moderators were sleep quality, mood states, perceived stress, and energy expenditure. Analyses were performed at baseline and months 12 and 24. RESULTS: After adjustments, there was a significantly greater improvement in working memory assessed by the SWM for CR individuals, compared to AL. At month 24, it was related mostly to lower protein intake, compared to other macronutrients. Changes in SWM were moderated by changes in sleep quality, physical activity, and energy expenditure. CONCLUSION: On the long term, CR in healthy individuals seems to have a slightly positive effect on working memory. The study of brain CR targets opens new possibilities to prevent and treat cognitive deficits.
Assuntos
Restrição Calórica/efeitos adversos , Memória de Curto Prazo , Adulto , Encéfalo/metabolismo , Encéfalo/fisiologia , Restrição Calórica/métodos , Cognição , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
El soporte nutricional que se brinda a los pacientes críticos, constituye para la mayoría la única vía de acceso a través de la cual es posible cubrir sus requerimientos nutricionales diarios. Sin embargo, se ha identificado que la presencia de deuda calórica impide cubrir dichos requerimientos. Este estudio determinó la deuda calórica y su potencial efecto clínico a través de una cohorte prospectiva que incluyó 191 pacientes que recibieron soporte nutricional en unidades de cuidado intensivo (UCI). Se evaluó la magnitud de la deuda calórica, los principales factores que la favorecen y se exploraron diferencias en desenlaces clínicos relacionados con mortalidad, complicaciones infecciosas y tiempo de estancia en UCI. Los resultados evidenciaron que la deuda calórica estuvo presente en el 73,8%(IC 95% = 67%-80%) de los pacientes evaluados; la principal causa estuvo relacionada con la interrupción de la nutrición enteral y no se encontró asociación entre el porcentaje de adecuación calórico y los desenlaces evaluados. Esta evaluación permitió establecer que la mayoría de los pacientes, a pesar de recibir soporte nutricional, se encuentran expuestos a deuda calórica siendo necesario generar estrategias de atención que permitan disminuir la exposición de esta población a dicha condición.
The nutritional support offered to critically ill patients is, for most of them, the only means to fulfill their daily nutritional requirements. However, it has been documented that nutritional support is not enough to cover such needs, due to the presence of caloric debt. We seek to determine the caloric debt and its potential to clinical affect critically ill patients that receive nutritional support in the Intensive Care Unit (ICU). We conducted a prospective cohort study with 191 patients. We assessed the magnitude of caloric debt and its related factors. We also explored variations in clinical outcomes related to mortality, infectious complications and ICU stay length. Caloric debt was found in 73.8% (95% CI = 67-80%) of patients who received less than 80% of their daily caloric requirements. Main causes were related to enteral nutrition interruption. We found no association between caloric debt and the evaluated outcomes. This evaluation made it possible to establish that the majority of patients, despite receiving nutritional support, were exposed to caloric debt, and it is necessary to generate care strategies to reduce the patients' exposure to this condition.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Nutrição Enteral , Nutrição Parenteral , Restrição Calórica/efeitos adversos , Unidades de Terapia Intensiva , Estudos Prospectivos , Fatores de Risco , Seguimentos , Estado Terminal , Apoio Nutricional , Ingestão de Alimentos , HospitalizaçãoRESUMO
Abstract Background: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. Objective: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. Methods: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). Results: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. Conclusion: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.
Resumo Fundamento: A restrição calórica compromete a função e a morfologia cardíacas em corações hipertrofiados de ratos espontaneamente hipertensos (SHR). No entanto, a influência de ciclo de jejum/Realimentação é desconhecida. Objetivo: Investigar o efeito de ciclos de jejum/realimentação sobre a remodelação e função miocárdica. Além disso, o presente estudo foi desenhado para avaliar os mecanismos subjacentes à participação do trânsito de cálcio (Ca+2) e sistema beta-adrenérgico. Métodos: Neste estudo, SHR machos de 60 dias de idade foram submetidos a alimento ad libitum (grupo C), 50% de restrição alimentar (grupo R50) ou ciclos de RF (grupo RF) por 90 dias. A remodelação cardíaca foi avaliada por meio da análise ultraestrutural e função do músculo papilar isolado. Adotou-se o nível de significância de 5% (a = 0,05). Resultados: Os ratos do grupo RF apresentaram menor atrofia cardíaca do que os do grupo R50 em relação aos do grupo C. Os ratos do grupo C aumentaram peso corporal, os ratos do grupo R50 mantiveram seu peso corporal inicial e os ratos do grupo RF aumentaram e reduziram seu peso durante o ciclo RF. O ciclo RF não causou comprometimento funcional, pois os parâmetros isotônicos e isométricos apresentaram comportamento similar aos dos ratos do grupo C. Os parâmetros cardíacos isotônicos e isométricos mostraram-se significativamente elevados nos ratos do grupo RF em comparação aos dos ratos do grupo R50. Além disso, os ratos do grupo R50 apresentaram dano cardíaco em comparação aos ratos do grupo C quanto às variáveis isotônicas e isométricas. Os ratos do grupo R50 apresentaram alterações focais em muitas fibras musculares, enquanto os ratos do grupo RF apresentaram leves alterações, como perda ou desorganização de miofibrilas. Conclusão: Ciclos de Jejum/Realimentação promovem efeitos benéficos cardíacos e atenuam o dano miocárdico causado por restrição calórica em SHR, contribuindo para reduzir o risco cardiovascular e os danos morfológicos. Além disso, o ciclo de jejum/realimentação promove leve melhora do trânsito do Ca2+ e do sistema beta-adrenérgico.
Assuntos
Animais , Masculino , Músculos Papilares/metabolismo , Cálcio/metabolismo , Jejum/fisiologia , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Cardiomiopatias/prevenção & controle , Músculos Papilares/patologia , Ratos Endogâmicos SHR , Fatores de Tempo , Peso Corporal/fisiologia , Cálcio/análise , Remodelação Ventricular/fisiologia , Restrição Calórica/efeitos adversos , Isoproterenol/análise , Isoproterenol/metabolismo , Contração Miocárdica , Cardiomiopatias/patologiaRESUMO
BACKGROUND: Caloric restriction is known to impair the cardiac function and morphology in hypertrophied hearts of spontaneously hypertensive rats (SHR); however, the influence of fasting/refeeding (RF) is unknown. OBJECTIVE: To investigate the fasting/refeeding approach on myocardial remodeling and function. In addition, the current study was designed to bring information regarding the mechanisms underlying the participation of Ca2+ handling and b-adrenergic system. METHODS: Sixty-day-old male SHR rats were submitted to food ad libitum (C), 50% food restriction (R50) or RF cycles for 90 days. Cardiac remodeling was assessed by ultrastructure analysis and isolated papillary muscle function. The level of significance considered was 5% (a = 0.05). RESULTS: The RF rats presented lower cardiac atrophy than R50 in relation to C rats. The C rats increased weight gain, R50 maintained their initial body weight and RF rats increased and decreased weight during RF. The RF did not cause functional impairment because the isotonic and isometric parameters showed similar behavior to those of C. The isotonic and isometric cardiac parameters were significantly elevated in RF rats compared to R50 rats. In addition, the R50 rats had cardiac damage in relation to C for isotonic and isometric variables. While the R50 rats showed focal changes in many muscle fibers, the RF rats displayed mild alterations, such as loss or disorganization of myofibrils. CONCLUSION: Fasting/refeeding promotes cardiac beneficial effects and attenuates myocardial injury caused by caloric restriction in SHR rats, contributing to reduce the cardiovascular risk profile and morphological injuries. Furthermore, RF promotes mild improvement in Ca2+ handling and b-adrenergic system.
Assuntos
Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Cálcio/metabolismo , Cardiomiopatias/prevenção & controle , Jejum/fisiologia , Músculos Papilares/metabolismo , Animais , Peso Corporal/fisiologia , Cálcio/análise , Restrição Calórica/efeitos adversos , Cardiomiopatias/patologia , Isoproterenol/análise , Isoproterenol/metabolismo , Masculino , Contração Miocárdica , Músculos Papilares/patologia , Ratos Endogâmicos SHR , Fatores de Tempo , Remodelação Ventricular/fisiologiaRESUMO
OBJECTIVE: We investigated the effect of intermittent food restriction (IFR) cycles on hypothalamic expression of lipogenic proteins and induction of overeating. METHODS: Female Wistar rats were distributed in three groups: free access to feed (control, C), 2 d feed restriction at 50% of C intake followed by 3 d (restricted 3, R3) or 5 d (restricted 5, R5) ad libitum feeding. After 6 wk, the rats were submitted to euthanasia and collected the hypothalamus and blood. The deposits of retroperitoneal, mesenteric, and gonadal fat were weighed. The expression of the mRNA for sterol regulatory element binding protein (SREBP) 1c and 2 and acetyl-CoA carboxylase in the hypothalamus were determined by real-time polymerase chain reaction, and glucose and triacylglycerol were evaluated by a commercial kit. Body mass and food intake were measured daily. RESULTS: IFR promoted increased expression of SREBP-2 in both treated groups and, in R5, increased expression of SREBP-1c. The serum triacylglycerol, mesenteric deposit, and total fat content were higher in R3. Neither of the treatment intervals altered the expression of the mRNA of acetyl-CoA carboxylase enzyme but induced hyperglycemia and higher food intake immediately after food restriction. CONCLUSION: IFR affected the expression of SREBP-1c in R5 and SREBP-2 in the hypothalamus and caused overeating immediately after fasting in both groups. We suggest that hypothalamic and peripheral alterations, coupled with compulsive eating behavior in the ad libitum period, indicate risks for diabetes mellitus and recovery of body mass after interruption of IFR.
Assuntos
Restrição Calórica/efeitos adversos , Ingestão de Alimentos/genética , Jejum/efeitos adversos , Hiperfagia/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , Feminino , Hiperfagia/etiologia , Hipotálamo/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
CONTEXT: Caloric restriction increases liver glucose release (LGR), but it is not known if this is a permanent condition. OBJECTIVE: To investigate if refeeding after caloric restriction reverses the high LGR. MATERIALS AND METHODS: Rats were organised in six-pups litters (GC); 12-pups litters with either 50% caloric restriction from 21 to 80 days of age (GR) or fed at will from 50 to 80 days of age (GRL). Liver perfusion was made at the age of 80 days. RESULTS: LGR was higher in the GR both during basal and adrenaline-stimulated conditions. Refeeding after caloric restriction decreased it to values close to those of GC rats. DISCUSSION: The altered LGR of GR rats was reversed by refeeding (group GRL). The influence of hypothalamic neuropetides on these hepatic changes is suggested. CONCLUSIONS: Enhanced LGR under caloric restriction is not programmed by early feeding; instead, it is determined by the current nutritional conditions.
Assuntos
Restrição Calórica/efeitos adversos , Regulação para Baixo , Glucose/metabolismo , Glicogenólise , Fígado/metabolismo , Síndrome da Realimentação/metabolismo , Animais , Glicemia/análise , Regulação para Baixo/efeitos dos fármacos , Epinefrina/farmacologia , Glicogenólise/efeitos dos fármacos , Cinética , Tamanho da Ninhada de Vivíparos , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Masculino , Perfusão , Ratos Wistar , Síndrome da Realimentação/sangue , Regulação para Cima/efeitos dos fármacos , Vasoconstritores/farmacologia , DesmameRESUMO
O desenvolvimento de uma resposta imune adequada é um processo extremamente importante para a manutenção da homeostase do organismo. Uma série de processos são desencadeados a partir do primeiro contato com micro-organismos patógenos até a efetivação da resposta imune de memória. Todos esses processos envolvem a participação e a complexa atuação de mediadores como as citocinas inflamatórias e também citocinas regulatórias, que exercerão efeitos controlando o processo inflamatório. Diversos mecanismos moleculares, subjacentes à resposta inflamatória, ainda não estão totalmente compreendidos, como por exemplo o controle da expressão de genes inflamatórios exercido pela IL-10. Os processos envolvidos na resposta inflamatória são mantidos às custas do consumo de nutrientes, dentre eles podemos destacar o aminoácido glutamina, que atua em nível molecular, fornecendo nitrogênio para a formação do material genético e fonte energética para determinadas células do sistema imunológico como os macrófagos. Portanto, neste trabalho, investigamos os efeitos da IL-10 na modificação de nucleossomos, evidenciando o papel dessa citocina em regular a expressão de genes inflamatórios em macrófagos. Avaliamos também a função da glutamina, modulando a expressão de RNAm de citocinas inflamatórias e regulatórias dessas células. E por último, desenvolvemos um modelo de restrição alimentar em camundongos, nos quais avaliamos os efeitos desse modelo considerando-se alguns aspectos hematológicos e estudamos as alterações na resposta inflamatória em células esplênicas e do peritônio, bem como avaliamos a suplementação de glutamina in vitro na produção das citocinas (IL-12, TNF-alfa, IL-10) e a expressão do fator de transcrição NFkB. Os resultados compilados mostraram que a IL-10 leva a uma rápida redução da acetilação de nucleossomos, modulando a arquitetura da cromatina de genes inflamatórios como a IL-12. A glutamina modula a expressão de citocinas inflamatórias, regulando positivamente a expressão de IL-10 e Interferon beta. E a restrição alimentar induz a redução de citocinas proinflamatórias (IL-12 e TNF-α), influenciadas pelo aumento da produção de IL-10 e finalmente a suplementação com glutamina não interfere nesses parâmetros nas células peritoneiais e esplênicas do grupo submetido à restrição alimentar. Conclusão: a IL-10 modula a expressão gênica através da modificação de nucleossomos em macrófagos derivados da medula; a glutamina modula a expressão de IL-10 inibindo a resposta inflamatória, e a restrição alimentar modula alguns aspectos hematológicos e possui propriedades anti-inflamatórias.
The development of an appropriate immune response is an important process to the organism's homeostatic maintenance. A series of processes are triggered upon the very first contact with pathogens, up to the immunological memory establishment. These processes implicate in the participation of complex mediators, such as inflammatory and regulatory cytokines that will control the inflammatory process. Some mechanisms underlying the inflammatory response are not totally understood, the control of inflammatory genes exerted by IL-10 is an example. The processes involved in the inflammatory response are kept with nutrients expense, among these nutrients we can highlight the amino acid glutamine. It acts in a molecular level, supplying nitrogen to genetic material formation and as an energy supply for immune cells such as macrophages. Thus, we investigated the IL-10 effects on nucleosome modifications evidencing this cytokine role regulating inflammatory genes expression in macrophages. We also evaluated glutamine functions modulating inflammatory and regulatory cytokines mRNA expression on these cells. Ultimately, we developed a dietary restriction animal model where we evaluated it's effects on selected haematological aspects, analyzing the alteration in the inflammatory response of splenic and peritoneal cells. We also evaluated in vitro glutamine supplementation assessing cytokines production (IL-12, TNF-α, and IL-10) and the expression of NFkB transcription factor. The compiled results a expressive reduction in nucleosome acetylation modifying the chromatin architecture of inflammatory genes such as IL-12 and IL-6. Glutamine modulates inflammatory cytokines gene expression upregulating the expression of IL-10 and interferon beta. The dietary restriction reduces proinflammatory cytokines production (IL-12 and TNF-α), these results are influenced by the upregulated IL-10 production, glutamine supplementation have no effect on these parameters in the dietary restriction group. In conclusion, we can infer that IL-10 modulates gene expression trough nucleosome modification in bone marrow derived macrophages, glutamine has a potential effect on IL-10 expression, inhibiting the inflammatory response and dietary restriction modifies hematological parameters, presenting anti-inflammatory properties.