Differential Responses of Liver and Hypothalamus to the Nutritional Condition During Lactation and Adult Life.

It was previously reported that liver glucose metabolism in rats under caloric restriction differs from that of freely-fed rats. This study hypothesized that these changes (1) were related to the expression of hypothalamic neuropeptides involved in metabolic control, and (2) were not a residual effect of litter size. To those purposes, liver glucose metabolism and hypothalamic expression of the orexigenic neuropeptides NPY (neuropeptide Y) and AgRP (agouti gene-related peptide); and of the anorexigenic neuropeptides POMC (pro-opiomelanocortin) and CART (cocaine- and amphetamine-related transcripts) were investigated. Male Wistar rats from two different litter sizes (G6 and G12, with 6 or 12 pups, respectively) were subjected to free feeding (GL, ad libitum), 50% caloric restriction (GR) or caloric restriction+ad libitum refeeding (GRL) until the age of 90 days. Biometric values were lower in GR than in GL, while in GRL they were totally or partially recovered. Blood glucose variation during the pyruvate tolerance test (PTT) was small in GR. During in situ liver perfusion, total, basal, and adrenaline-stimulated liver glucose outputs were high in GR, but additional glucose output in the presence of alanine was negligible. Refeeding (GRL) yielded values close to those of GL. Litter size did not consistently influence any of these variables. The expression of transcripts of the hypothalamic neuropeptides was responsive to feeding regimen, litter size and/or their interaction and differed from G6 to G12, while the metabolic changes of the liver were qualitatively equal in both GR. Therefore, the changes in glucose metabolism in the liver of rats under caloric restriction were not determined by either litter size or hypothalamic neuropeptide expression and were linked only to the prevailing feeding regimen of the adult animal.

Modulation of liver glucose output by free or restricted feeding in the adult rat is independent of litter size.

BACKGROUND: Caloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible. It was investigated whether these changes could be a residual effect of the nutritional condition during lactation and what could be the mechanism of such change. METHODS: Newborn Wistar rat pups were arranged in litters of 6 or 12 (G6 and G12). After weaning, the male pups were divided in: G6L and G12 L, fed freely until the age of 90 days (freely-fed groups); G6R and G12R, given 50% of the GL ingestion (food-restricted groups) until 90 days of age; G6RL and G12RL, given 50% of the GL ingestion until 60 days of age and fed freely until 90 days of age (refed groups). The experimental protocols were carried out at the age of 90 days after overnight fasting. Pairs of groups were compared through t test; other statistical comparisons were made with one-way ANOVA with Tukey post hoc text. RESULTS: Caloric restriction was effective in decreasing body and fat weights, total cholesterol and LDL. These effects were totally or partially reversed after 30 days of refeeding (groups GRL). During liver perfusion, the high glucose output of the GRs was further enhanced by adrenaline (1 µM), but not by lactate infusion. In contrast, in groups G6L, G12 L, G6RL and G12RL glycogenolysis (basal and adrenaline-stimulated glucose output) was low and gluconeogenesis from lactate was significant. A twofold increase in liver content of PKA in group G6R suggests that liver sensitivity to glucagon and adrenaline was higher because of caloric restriction, resulting in enhanced glucose output. CONCLUSIONS: As glucose output was not affected by litter size, liver glucose metabolism in the adult rat, in contrast to other metabolic processes, is not a programmed effect of the nutritional condition during lactation. In addition, the increased expression of PKA points to a higher sensitivity of the animals under caloric restriction to glycogenolytic hormones, a relevant condition for glucose homeostasis during fasting.

Food restriction promotes damage reduction in rat models of type 2 diabetes mellitus.

There are several animal models of type 2 diabetes mellitus induction but the comparison between models is scarce. Food restriction generates benefits, such as reducing oxidative stress, but there are few studies on its effects on diabetes. The objective of this study is to evaluate the differences in physiological and biochemical parameters between diabetes models and their responses to food restriction. For this, 30 male Wistar rats were distributed in 3 groups (n = 10/group): control (C); diabetes with streptozotocin and cafeteria-style diet (DE); and diabetes with streptozotocin and nicotinamide (DN), all treated for two months (pre-food restriction period). Then, the 3 groups were subdivided into 6, generating the groups CC (control), CCR (control+food restriction), DEC (diabetic+standard diet), DER (diabetic+food restriction), DNC (diabetic+standard diet) and DNR (diabetic+food restriction), treated for an additional two months (food restriction period). The food restriction (FR) used was 50% of the average daily dietary intake of group C. Throughout the treatment, physiological and biochemical parameters were evaluated. At the end of the treatment, serum biochemical parameters, oxidative stress and insulin were evaluated. Both diabetic models produced hyperglycemia, polyphagia, polydipsia, insulin resistance, high fructosamine, hepatic damage and reduced insulin, although only DE presented human diabetes-like alterations, such as dyslipidemia and neuropathy symptoms. Both DEC and DNC diabetic groups presented higher levels of protein carbonyl groups associated to lower antioxidant capacity in the plasma. FR promoted improvement of glycemia in DNR, lipid profile in DER, and insulin resistance and hepatic damage in both diabetes models. FR also reduced the protein carbonyl groups of both DER and DNR diabetic groups, but the antioxidant capacity was improved only in the plasma of DER group. It is concluded that FR is beneficial for diabetes but should be used in conjunction with other therapies.

Metabolismo do lactato e avaliação de desempenho: dois lados do mesmo processo / Lactate metabolism and performance assessment: two sides of the same process

A mensuração do lactato sanguíneo com determinação do limiar anaeróbio é uma forma simples e difundida de avaliar o desempenho físico. O lactato é o produto final da glicólise anaeróbia, um dos processos geradores de energia no corpo humano, junto com os sistemas dos fosfagênios e aeróbio. A contribuição relativa de cada um deles para as demandas energéticas do músculo esquelético depende do tipo, intensidade e duração do exercício, e o lactato é uma forma de medir essa contribuição. Há intensa transferência de lactato entre tecidos e dentro das células musculares. O propósito desta revisão é interligar esses aspectos em uma estrutura coerente a partir da qual novas hipóteses possam ser exploradas. Foram consultados artigos das bases PubMed e Scielo usando os termos treinamento, performance, lactato e metabolismo e livros de fisiologia. O metabolismo sistêmico de lactato e a variação sanguínea do lactato, registrada em avaliações de desempenho, são aspectos inter-relacionados do mesmo processo fisiológico.

The measuring of blood lactate to determine anaerobic threshold is the commonest method to evaluate physical performance. Lactate is the final product of anaerobic glycolysis, one of the energy-producing processes in the human body, coupled to phosphagenic and aerobic systems. Since relative contribution of each for energy demands of the skeleton muscle depends on the type, intensity and duration of the exercise, lactate measures such contribution. There is intense transfer of lactate among tissues and within muscle cells. This review interlinks the above aspects within a coherent structure so that new hypotheses may be taken. Physiology textbooks and articles from PubMed and Scielo databases were consulted by employing the terms training, performance, lactate and metabolism. Lactate systemic metabolism and lactate blood variation registered in performance assessments are inter-related aspects of the same physiological process.

Early-onset obesity and food restriction alter hepatocyte metabolism in adult Wistar rats.

CONTEXT: Caloric restriction (CR) is suggested for overweight control. OBJECTIVE: Systemic and liver glucose metabolism in the reduced-litter (RL) rat model under 30% CR was investigated. MATERIALS AND METHODS: Newborn litters were organised in control (G9); RL with free diet (G3L); and RL with CR (G3R). Assessments were made at the age of 90 d. RESULTS: Higher liver glycogen content and changes in systemic glucose handling were found in the RL groups. Hepatocyte glucose metabolism was similar in groups G9 and G3L, but basal glucose production and glycogenolysis were higher, while gluconeogenesis and basal glycolysis were lower in the G3R. Urea production was lower in the RL groups. DISCUSSION: The altered glucose handling of the RL adult rats was not reversed by moderate (30%) CR. Hepatocyte glucose and nitrogen metabolism were changed by both early overfeeding and current feeding conditions. CONCLUSIONS: RL and CR alter systemic and liver glucose metabolism.

Fisiologia de extremos: Digestão em répteis de alimentação esporádica / Extreme physiology: Digestion in intermittent-feeding reptiles / Fisiología de extremos: Digestión en reptiles de alimentación esporádica

Entre as diversas adaptações que os seres vivos apresentam em resposta às variáveis do ambiente, estão as mudanças adaptativas morfológicas e funcionais a curto e longo prazo que acontecem no sistema digestório em resposta ao padrão de alimentação. Em alguns répteis, tais adaptações vêm ao encontro da maximização dos recursos energéticos, os quais correlacionam os hábitos alimentares ao rendimento energético por meio do processo de regulação de órgãos específicos. Considerável número de artigos discute o desempenho do trato gastrointestinal e a influência de outros sistemas no auxílio a esse comportamento do sistema digestório em répteis, especialmente em pítons. Este trabalho teve por objetivo destacar e discutir as ações fisiológicas envolvidas no processo digestório e em outros sistemas em répteis que se alimentam esporadicamente. A atrofia e reconstrução alternadas do trato gastrointestinal em animais de hábitos alimentares infrequentes garantem a esses uma economia de energia em períodos de jejum e uma alta captação dos nutrientes no período digestivo. Essas alterações são acompanhadas por variações funcionais ácido-básicas, respiratórias e hemodinâmicas, e consequentemente por grandes mudanças na taxa metabólica, quando os estados de jejum e pós-prandial são comparados.

Short- and long-term morphological and functional adaptive changes in the digestive system related to the feeding habits are among the many adaptations living beings have in response to environmental variables. In some reptiles, such adaptations aim at maximizing the energy resources, which correlate the feeding habits with the energy performance through the regulation of specific organs. A considerable number of articles address the performance of the digestive tract and the influence of other systems in helping this digestive system behavior in reptiles, especially pythons. This paper has the purpose of highlighting and discussing the physiological actions involved in the digestive process and in other systems in reptiles that feed sporadically. The alternate atrophy and reconstruction of the gastrointestinal system in infrequent-feeding animals allow them to save energy during fasting and a high uptake of nutrients during digestion. These changes are accompanied by acid-base, respiratory and hemodynamic alterations, and therefore, by large changes in the metabolic rate, when comparing fasting and the post-prandial periods.

Entre las diversas adaptaciones que los seres vivos tienen, en respuesta a las variables ambientales, están los cambios adaptativos morfológicos y funcionales a corto y largo plazo que se producen en el sistema digestivo en respuesta al patrón de alimentación. En algunos reptiles, tales adaptaciones vienen a satisfacer la maximización de los recursos energéticos, que correlacionan los hábitos alimenticios con la eficiencia energética a través del proceso de regulación de órganos específicos. Números considerables de artículos analizan el rendimiento del tracto gastrointestinal y la influencia de otros sistemas para ayudar al sistema digestivo en los reptiles, especialmente las pitones. Este estudio tuvo como objetivo destacar y discutir las acciones fisiológicas que intervienen en el proceso digestivo y en otros sistemas en reptiles que se alimentan de forma esporádica. La atrofia y la reconstrucción alternadas del tracto gastrointestinal de animales de hábitos alimentarios infrecuentes, aseguran tales ahorros de energía durante los períodos de ayuno y una alta absorción de nutrientes en el período digestivo. Estos cambios van acompañados de variaciones funcionales ácido-básico, respiratorias y hemodinámicos y, consecuentemente por importantes cambios en la tasa metabólica, cuando se comparan los estados de ayuno y postprandial.

Acute exercise and caffeine improve insulin-induced hypoglycemia in normal and malnourished rats / Exercício agudo e cafeína melhoram a hipoglicemia induzida por insulina em ratos normais e desnutridos

In food restriction, hypoglycemic episodes can be more severe and persistent. This study assessed the influence of acute exercise and caffeine on the insulin-induced hypoglycemia in freely-fed or malnourished (50% food restriction) young rats. At the age of 60 days, rats under overnight fasting received an insulin injection to cause an episode of hypoglycemia. In some animals, hypoglycemia was preceded by an acute session of exercise, in others, caffeine was orally given 15 minutes after insulin injection; or exercise and caffeine were combined. Blood samples were collected at regular intervals for five hours after insulin injection. A beneficial effect of both exercise or caffeine on the hypoglycemic episode in the malnourished rats was found. In the control rats, the association of exercise+caffeine was more beneficial than either intervention alone. It is discussed that exercise and caffeine, alone or combined, can be used as exogenous anti-hypoglycemic resources, but considering the nutritional status of the subject.

Na restrição alimentar, os episódios de hipoglicemia podem ser mais severos e persistentes. Este trabalho avaliou a influência do exercício agudo e da cafeína sobre a hipoglicemia induzida por insulina em ratos jovens alimentados livremente ou desnutridos (50% de restrição alimentar) desde o nascimento. Aos 60 dias de idade, os ratos em jejum noturno receberam injeção de insulina para causar um episódio de hipoglicemia. Em alguns animais, a hipoglicemia foi precedida por sessão aguda de exercício; em outros foi administrada a cafeína via oral, 15 min. após a injeção de insulina; ou foi associada a exercício e cafeína. Amostras de sangue foram coletadas em intervalos regulares por 5h desde a aplicação da insulina. Registrou-se efeito benéfico do exercício e da cafeína isolados sobre o episódio hipoglicêmico nos ratos desnutridos. Nos ratos controle, a associação de exercício+cafeína teve efeito benéfico mais acentuado do que as intervenções separadas. É discutido que exercício físico e cafeína, isolados ou combinados, podem ser explorados como recursos anti-hipoglicêmicos exógenos, levando-se em consideração porém o estado nutricional do indivíduo.

Effect of the chronic administration of caffeine on adipose mass and lipid profile of Wistar rats / Efeito da administração crônica de cafeína na massa adiposa e no perfil lipídico de ratos Wistar

This work aimed at verifying the effect of the chronic ingestion of caffeine on body weight and adiposity of Wistar rats. Sixteen male Wistar rats weighting on average 240 g were divided into two groups, one control and the other caffeine -treated (5 mg kg-1, orally) for five weeks. At the end, the groups were evaluated for their differences in body weight; weight of the periepididymal, retroperitoneal, subcutaneous and mesenteric fat pads; size of the retroperitoneal adipocytes; liver and heart weight; glycemia and plasma lipids. Statistically significant differences were observed in adipocyte size and total serum cholesterol, while the results for the other parameters were not statistically different. Therefore, this study showed that, using an oral dose of caffeine within acceptable (non toxic) limits, it is possible to reduce the size of adipocytes of non-obese Wistar rats, as well as to reduce the serum cholesterol levels, even in the absence of physical activity or other active compounds.

Este trabalho teve como objetivo verificar o efeito da ingestão crônica de cafeína no peso corporal e na adiposidade de ratos Wistar. Foram utilizados 16 ratos Wistar machos com peso em torno de 240 g divididos em dois grupos, um controle e outro tratado com cafeína (5 mg kg-1, via oral) por cinco semanas. Ao final, foi avaliada a diferença entre os dois grupos em relação ao peso corporal; ao peso dos depósitos de gordura periepididimal, retroperitoneal, subcutânea e mesentérica; ao tamanho dos adipócitos retroperitoneais; ao peso do coração e do fígado; e aos valores de glicemia e lipídeos plasmáticos. Foram observadas diferenças estatisticamente significativas no tamanho dos adipócitos e na quantidade plasmática de colesterol total, sendo que o resultado das demais variáveis não foi significativo. Portanto, este estudo mostrou que, usando uma dose oral de cafeína dentro dos limites considerados aceitáveis (não-tóxicos), é possível reduzir o tamanho dos adipócitos de ratos Wistar não-obesos, bem como reduzir seus níveis séricos de colesterol, mesmo na ausência de atividade física ou de outros compostos ativos.