Chronic REM sleep restriction in young rats increases energy expenditure with no change in food intake.

NEW FINDINGS: What is the central question of this study? What are the effects of different periods of REM sleep restriction (7, 14 and 21 days) on metabolic parameters in young rats? What is the main finding and its importance? Animals submitted to each period of REM sleep deprivation showed a negative energy balance, with reduced body weight gain, body energy gain and gross food efficiency, less body fat content, and increased energy expenditure. There was no increase in food intake after any of the REM sleep restriction periods. In young rats, negative energy balance is not compensated by increased dietary intake as observed in adult rats. ABSTRACT: Reduced sleep is associated with metabolic alterations, not only in adults, but also in children and adolescents. Several studies have shown that sleep restricted (SR) adult rats exhibit metabolic changes, followed by increased food intake, but few have evaluated these functions in young animals. The aim of the present study was to establish the metabolic parameters of young rats subjected to different periods of REM sleep restriction and to propose a correction factor for the correct measurement of food intake. Young male Wistar rats were distributed in control and SR groups for 7, 14 or 21 days. Sleep restriction was performed by the single platform method for 18 h. Regardless of the length of sleep restriction, all SR rats had a negative energy balance, evidenced by reduction in body weight gain, body energy gain and gross food efficiency, accompanied by increased energy expenditure. In addition, sleep restriction reduced body fat content throughout the entire period. Discounting food spillage, there was no increase in food intake by SR rats. In conclusion, the present study revealed metabolic changes in SR young rats after different lengths of REM sleep restriction and that weight loss and increased energy expenditure were not compensated by increased dietary intake as occurs in adult rats, indicating that young rats use other mechanisms to cope with the negative energy balance caused by sleep restriction. In addition, we propose a correction factor for food intake, to prevent overestimation of this parameter, due to food spillage in the water containers.

Restriction of rapid eye movement sleep during adolescence increases energy gain and metabolic efficiency in young adult rats.

NEW FINDINGS: What is the central question of this study? Sleep curtailment in infancy and adolescence may lead to long-term risk for obesity, but the mechanisms involved have not yet been determined. This study examined the immediate and long-term metabolic effects produced by sleep restriction in young rats. What is the main finding and its importance? Prolonged sleep restriction reduced weight gain (body fat stores) in young animals. After prolonged recovery, sleep-restricted rats tended to save more energy and to store more fat, possibly owing to increased gross food efficiency. This could be the first step to understand this association. Sleep curtailment is associated with obesity and metabolic changes in adults and children. The aim of the present study was to evaluate the immediate and long-term metabolic alterations produced by sleep restriction in pubertal male rats. Male Wistar rats (28 days old) were allocated to a control (CTL) group or a sleep-restricted (SR) group. This was accomplished by the single platform technique for 18 h per day for 21 days. These groups were subdivided into the following four time points for assessment: sleep restriction and 1, 2 and 4 months of recovery. Body weight and food intake were monitored throughout the experiment. At the end of each time period, blood was collected for metabolic profiling, and the carcasses were processed for measurement of body composition and energy balance. During the period of sleep restriction, SR animals consumed less food in the home cages. This group also displayed lower body weight, body fat, triglycerides and glucose levels than CTL rats. At the end of the first month of recovery, despite eating as much as CTL rats, SR animals showed greater energy and body weight gain, increased gross food efficiency and decreased energy expenditure. At the end of the second and fourth months of recovery, the groups were no longer different, except for energy gain and gross food efficiency, which remained higher in SR animals. In conclusion, sleep restriction affected weight gain of young animals, owing to reduction of fat stores. Two months were sufficient to recover this deficit and to reveal that SR rats tended to save more energy and to store more fat.

Maternal obesity and late effects on offspring metabolism.

OBJECTIVE: The aim of this study was to evaluate the late effects of maternal obesity induced by lesion of the ventromedial hypothalamus on offspring metabolism. MATERIALS AND METHODS: Thirty days after the bilateral lesion of the ventromedial hypothalamus, female rats were mated and divided into 2 groups of pregnant animals: Control (C) - false lesion (sham) and Obese (OB) - lesion. Three months after that, with the groups of mothers, offspring were divided into control and obese animals that received a normocaloric diet (C-N and OB-N), and control and obese animals that received a hypercaloric diet (C-H and OB-H). At 120 days of age, the animals were euthanized and their carcasses, feces and food were submitted to calorimetric analysis to determine energy balance and body composition. RESULTS: During the growth period, offspring from obese mothers showed higher values of body weight and food intake than controls. Obese animals showed higher body weight gain and gross food efficiency than control animals in adulthood. The hypercaloric diet led to increased metabolizable energy intake, percentage of absorbed energy and energy expenditure in both groups. Body composition was only affected by the association of hypercaloric diet and maternal obesity that led to increased body fat. CONCLUSIONS: Maternal obesity has led to the development of later overweight in offspring, suggesting fetal programming. According to the trend presented, it is believed that the prolonged intake of hypercaloric diets in adult animals may, as an additional effect, induce worsening of the overweight induced by maternal obesity.

Maternal obesity and late effects on offspring metabolism / Obesidade materna e efeitos tardios sobre o metabolismo da prole

Objective : The aim of this study was to evaluate the late effects of maternal obesity induced by lesion of the ventromedial hypothalamus on offspring metabolism.Materials and methods : Thirty days after the bilateral lesion of the ventromedial hypothalamus, female rats were mated and divided into 2 groups of pregnant animals: Control (C) – false lesion (sham) and Obese (OB) – lesion. Three months after that, with the groups of mothers, offspring were divided into control and obese animals that received a normocaloric diet (C-N and OB-N), and control and obese animals that received a hypercaloric diet (C-H and OB-H). At 120 days of age, the animals were euthanized and their carcasses, feces and food were submitted to calorimetric analysis to determine energy balance and body composition.Results : During the growth period, offspring from obese mothers showed higher values of body weight and food intake than controls. Obese animals showed higher body weight gain and gross food efficiency than control animals in adulthood. The hypercaloric diet led to increased metabolizable energy intake, percentage of absorbed energy and energy expenditure in both groups. Body composition was only affected by the association of hypercaloric diet and maternal obesity that led to increased body fat.Conclusions : Maternal obesity has led to the development of later overweight in offspring, suggesting fetal programming. According to the trend presented, it is believed that the prolonged intake of hypercaloric diets in adult animals may, as an additional effect, induce worsening of the overweight induced by maternal obesity. Arq Bras Endocrinol Metab. 2014;58(3):301-7.

Objetivo Avaliar os efeitos tardios da obesidade materna induzida por lesão do núcleo ventromedial do hipotálamo sobre o metabolismo da prole. Trinta dias após a lesão bilateral do hipotálamo ventromedial, ratos fêmeas foram colocadas para acasalar e divididas em dois grupos de animais gestantes: Controle (C) – falsa lesão e Obeso (OB) – lesionados. Três meses após o nascimento, de acordo com os grupos das mães, os filhotes foram divididos em animais controle e obesos que recebiam dieta normocalórica (C-N and OB-N) e animais controle e obesos que recebiam dieta hipercalórica (C-H and OB-H). Aos 120 dias de idade, os animais foram eutanasiados e as carcaças, fezes e ração foram submetidas à análise calorimétrica para determinação do balanço energético e composição corporal.Resultados Durante o período de crescimento, os filhos de mães obesas mostraram maiores valores de peso corporal e ingestão alimentar que animais controle. Os animais obesos apresentaram maiores valores de ganho de peso corporal e eficiência metabólica que os animais controle quando adultos. A dieta hipercalórica levou ao aumento da energia metabolizável, percentagem de energia absorvida e gasto energético para ambos os grupos. A composição corporal foi somente afetada pela associação da dieta hipercalórica com a obesidade materna que levou ao aumento da gordura corporal.Conclusões : A obesidade materna levou ao sobrepeso tardio na prole, sugerindo uma programação fetal. Pela tendência apresentada, acreditamos que a ingestão prolongada de dietas hipercalóricas em animais adultos possa induzir uma piora no quadro de sobrepeso induzido pela obesidade materna. Arq Bras Endocrinol Metab. 2014;58(3):301-7.

Effect of food restriction on energy expenditure of monosodium glutamate-induced obese rats.

The neonatal administration of monosodium glutamate (MSG) to rodents leads to obesity in the adult animal, characterized by increased fat storages. Chronic food restriction is known to induce reduction in body energy expenditure, as an adaptive mechanism to save energy. Our purpose was to examine whether obesity can alter the mechanism of energy conservation in food-restricted animals. Newborn female Wistar rats were injected either MSG (obese) or saline (control). At the age of 90 days, the animals were fed daily ad libitum (control and MSG) or restricted (50%) (control-restricted and MSG-restricted). After 30 days the animals were sacrificed and the energy balance was determined by calorimetric analysis. Some parameters of energy balance and body composition were affected by MSG treatment as well as food restriction. The percent reduction of the energy expenditure and fat content in MSG-restricted animals was lower than control-restricted animals, when compared with their respective ad libitum groups. These results indicate that all food-restricted animals were able to develop the mechanism of energy conservation, regardless of the obesity, but it was less efficient in MSG-obese animals.

Iron absorption from infant formula and iron-fortified cow's milk: experimental model in weanling rats.

OBJECTIVE: To compare iron absorption from infant formula and iron-fortified cow's milk. METHODS: Twenty-four weanling Wistar rats were maintained in metabolic cages during the whole experiment (10 days). On the first day, the animals were divided into three similar groups according to their weight, length, hematocrit and hemoglobin levels: 1) infant formula; 2) powdered whole cow's milk fortified with iron in the same quantity and type as the formula; 3) control--powdered whole cow's milk not fortified with iron. Deionized water and diet were offered ad libitum and the volume consumed was measured. Weight, hematocrit, and hemoglobin levels were measured on the fifth and 10th days when length, fecal occult blood, and hepatic iron levels were also analyzed. RESULTS: Group 1 consumed less diet (450.5+/-26.50 mL) than group 2 (658.8+/-53.73 mL) and control group (532.7+/-19.06 mL, p < 0.001). Hemoglobin levels were higher (p < 0.001) in group 1 (12.1+/-1.13 g/dL) than in group 2 (9.6+/-1.59 g/dL) and in control group (6.2+/-0.97 g/dL). Hepatic iron level showed the same pattern as hemoglobin (p < 0.001). There was no difference in weight and length between the three groups (p = 0.342). There was no fecal occult blood in the any of the animals. CONCLUSIONS: Despite the lower volume consumed, the group that received formula presented higher iron absorption and hemoglobin levels than the group fed with fortified whole cow's milk. Growth was similar in the three groups.

Absorção do ferro da fórmula para lactentes e do leite de vaca fortificado: modelo experimental em ratos recém-desmamados / Iron absorption from infant formula and iron-fortified cow's milk: experimental model in weanling rats

OBJETIVO: Comparar a absorção do ferro da fórmula de partida e do leite de vaca integral fortificado. MÉTODOS: Foram utilizados 24 ratos machos Wistar recém-desmamados, mantidos em gaiolas metabólicas durante todo o período do experimento (10 dias). No primeiro dia, os animais foram distribuídos em três grupos semelhantes quanto ao peso, comprimento, hematócrito e hemoglobina: 1) fórmula de partida para lactentes; 2) leite de vaca integral em pó fortificado com a mesma quantidade e tipo de sal de ferro da fórmula; e 3) controle - leite de vaca integral em pó não fortificado com ferro. Água e dieta foram oferecidas ad libitum com mensuração do volume consumido. Peso, hematócrito e hemoglobina foram mensurados no quinto e no 10º dia do experimento, quando foram analisados também comprimento, sangue oculto nas fezes e teor de ferro hepático. RESULTADOS: O grupo 1 ingeriu menor volume de dieta (450,5±26,50 mL) que os grupos 2 (658,8±53,73 mL) e controle (532,7±19,06 mL; p < 0,001). As concentrações de hemoglobina foram maiores (p < 0,001) no grupo 1 (12,1±1,13 g/dL) que nos grupos 2 (9,6±1,59 g/dL) e controle (6,2±0,97 g/dL). O teor de ferro hepático apresentou o mesmo comportamento da hemoglobina (p < 0,001). Não foi observada diferença de peso e comprimento nos três grupos (p = 0,342). Não foi detectado sangue oculto nas fezes de nenhum dos animais. CONCLUSÕES: Apesar do menor volume ingerido, o grupo que recebeu fórmula apresentou maior absorção de ferro e concentração de hemoglobina que o grupo que recebeu leite de vaca integral fortificado. O crescimento foi semelhante nos três grupos.

OBJECTIVE: To compare iron absorption from infant formula and iron-fortified cow's milk. METHODS: Twenty-four weanling Wistar rats were maintained in metabolic cages during the whole experiment (10 days). On the first day, the animals were divided into three similar groups according to their weight, length, hematocrit and hemoglobin levels: 1) infant formula; 2) powdered whole cow's milk fortified with iron in the same quantity and type as the formula; 3) control - powdered whole cow's milk not fortified with iron. Deionized water and diet were offered ad libitum, and the volume consumed was measured. Weight, hematocrit, and hemoglobin levels were measured on the fifth and 10th days when length, fecal occult blood, and hepatic iron levels were also analyzed. RESULTS: Group 1 consumed less diet (450.5±26.50 mL) than group 2 (658.8±53.73 mL) and control group (532.7±19.06 mL, p < 0.001). Hemoglobin levels were higher (p < 0.001) in group 1 (12.1±1.13 g/dL) than in group 2 (9.6±1.59 g/dL) and in control group (6.2±0.97 g/dL). Hepatic iron level showed the same pattern as hemoglobin (p < 0.001). There was no difference in weight and length between the three groups (p = 0.342). There was no fecal occult blood in the any of the animals. CONCLUSIONS: Despite the lower volume consumed, the group that received formula presented higher iron absorption and hemoglobin levels than the group fed with fortified whole cow's milk. Growth was similar in the three groups.

Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity.

OBJECTIVE: Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown. RESEARCH DESIGN AND METHODS: Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity. RESULTS: Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet. CONCLUSIONS: Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats.

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in anti-hypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases.

High- or low-salt diet from weaning to adulthood: effect on body weight, food intake and energy balance in rats.

OBJECTIVE: To get some additional insight on the mechanisms of the effect of salt intake on body weight. DESIGN AND METHODS: Rats were fed a low (LSD), normal (NSD), or high (HSD) salt diet. In a first set, body weight, tail-cuff blood pressure, fasting plasma thyroid-stimulating hormone, triiodothyronine, L-thyroxine, glucose, insulin, and angiotensin II were measured. Angiotensin II content was determined in white and brown adipose tissues. Uncoupling protein 1 expression was measured in brown adipose tissue. In a second set, body weight, food intake, energy balance, and plasma leptin were determined. In a third set of rats, motor activity and body weight were evaluated. RESULTS: Blood pressure increased on HSD. Body weight was similar among groups at weaning, but during adulthood it was lower on HSD and higher on LSD. Food intake, L-thyroxine concentration, uncoupling protein 1 expression and energy expenditure were higher in HSD rats, while non-fasting leptin concentration was lower in these groups compared to NSD and LSD animals. Plasma thyroid-stimulating hormone decreased on both HSD and LSD while plasma glucose and insulin were elevated only on LSD. A decrease in plasma angiotensin II was observed in HSD rats. On LSD, an increase in brown adipose tissue angiotensin II content was associated to decreased uncoupling protein 1 expression and energy expenditure. In this group, a low angiotensin II content in white adipose tissue was also found. Motor activity was not influenced by the dietary salt content. CONCLUSIONS: Chronic alteration in salt intake is associated with changes in body weight, food intake, hormonal profile, and energy expenditure and tissue angiotensin II content.

Energy balance of pregnant diabetic rats.

Pregnancy and diabetes lead to metabolic alterations in the energy balance that may not be completely independent. The objective of the present study was to look at the alterations induced by type 1 diabetes mellitus on the energy balance of pregnant rats and the offspring. Diabetes was induced by streptozotocin injection 15 d before the starting of pregnancy. The rats had their energy balance variables followed for 21 d. Protein, fat and energy content of dams was determined from samples of the carcasses. Pregnancy led to increased energy intake, energy gain and energy expenditure as well as higher gross food efficiency than non-pregnant counterparts. Diabetes increased metabolizable energy intake but not the energy gain of the animals: they had very high energy expenditure, so that diabetes blocked the improvement in gross food efficiency shown during pregnancy. Offspring from diabetic dams were born with lower body weight. Pregnant animals did not present the usual energy storage as seen by lower energy gain of diabetic dams as well as by the lower fat content in the carcasses of pregnant diabetic rats. It is concluded that diabetes impairs the energy variables usually enhanced by pregnancy alone.