Jacqueline Luz

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.

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 B1 and B2. 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 B1 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 B1 receptor deficiency in mice (B1−/−) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet–induced weight gain. Under high-fat diet, B1−/− also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B1 receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B1−/−). However, ob/ob-B1−/− mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B1 receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B1 receptor ablation was pharmacologically confirmed by long-term administration of the kinin B1 receptor antagonist SSR240612 to mice under high-fat diet. CONCLUSIONS—Our data suggest that kinin B1 receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.

Enhanced peroxisomal β-oxidation is associated with prevention of obesity and glucose intolerance by fish oil-enriched diets

The effects of different amounts of omega 3—polyunsaturated fatty acids in diets with normal or high content of fat on lipid and carbohydrate metabolism were investigated.

The Influence of Food Restriction During Different Periods of Pregnancy

Considering that the energy balance can be affected by factors such as pregnancy and food restriction and that the development of foetuses is different during different periods of pregnancy, the aim of this paper was to study the effects on the maternal and offspring energy balance of food restriction imposed at different periods of pregnancy. Pregnant and non-pregnant rats were subjected to four food intake treatments. Control groups received food ad libitum during the 20 days of the experiment. The other three groups were food restricted by receiving 50% of the control group food intake during the first half, the second half, or the whole experimental period. Food restriction imposed during the first half of the experimental period permitted a recuperation of energy intake, but compared to the control group, the rats gained less energy in the body. The offspring parameters studied were not affected by food restriction during the first half of the experimental period. Food restriction during the second half was more deleterious to the dams and to the offspring, which were born with less energy and weight. When food restriction was applied during the whole experimental period, the impairment in energy balance of offspring was similar to the one observed when food restriction occurred during the second half of pregnancy added to a decreased number of offspring. The dams, however, were more deeply affected than when food restriction was applied during the first half of the experimental period.

Distribution of Energy between Food-Restricted Dams and Offspring

Pregnant and nonpregnant rats were subjected to one of four food intake schedules: ad libitum, 20, 40 and 60% of food restriction, during 20 days, with the objective of studying the distribution of energy between food-restricted mothers and offspring. The animals were anesthetized and the conceptuses were removed and separated into male, female, and placental tissues. The rats were then killed and all carcasses were prepared for energy balance determination. A baseline group of weight-matched rats were killed in the first day of the experiment to evaluate the initial body energy. The results obtained showed that the energy balance of pregnant rats was impaired as a consequence of the food restriction imposed. The offspring from restricted mothers had lower body weight and energy content and were less in number than the ones from the control dams. It is also suggested that food restriction causes the mother to transfer similar percent energy to the offspring as in control animals which will deplete the mother energy stores more than in ad libitum fed rats.

Oxygen consumption of rats with broad intestinal resection

The study was performed to investigate possible alterations in oxygen consumption in an animal model with broad intestinal resection. Oxygen consumption and the thermal effect of a short meal were measured in rats subjected to short bowel syndrome. Four groups of rats were used. Group I was the control group, group II was sham operated, group III was submitted to 80% jejunum-ileum resection, and group IV was submitted to 80% jejunum-ileum resection with colon interposition. Ninety days after surgery, oxygen consumption was measured over a period of 6 h with the animals fasted overnight. The thermal effect of feeding was determined in another session of oxygen consumption measurement in animals fasted for 12 h. A 12-kcal meal was then introduced into the animal chamber and oxygen consumption was measured for a further 4 h. No differences in fasting oxygen consumption or in the thermal effect of the meal were detected among the groups studied. It is concluded that short bowel syndrome does not affect the overall energy expenditure of rats.

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.

Effects of Aging on the Energy Balance of Pregnant Rats

In pregnant and non-pregnant female rats at various ages the energy balance was determined to study the age-induced alterations in the mother and conceptus. The animals were anesthetized and the conceptus removed and separated into male, female, and placental tissues. The animals were then killed and the carcasses prepared for energy balance determination. The results obtained showed that the older animals gained less energy in the body and had lower gross food efficiency than the younger animals. The number, energy and weight of the offspring were not affected by the mother’s age. Nevertheless, due to its constant growth during life, the rat is not the best model to study age-related processes.

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 cows 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 cows milk fortified with iron in the same quantity and type as the formula; 3) control--powdered whole cows 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 cows milk. Growth was similar in the three groups.

Chronic lipoic acid treatment worsens energy imbalances in streptozotocin-induced diabetic rats

AIM Our objective was to verify the energy balance in streptozotocin-induced diabetic rats chronically treated with lipoic acid (LA). METHODS Diabetes was induced in rats by streptozotocin and the animals divided into four groups, comprising controls and diabetic rats, with each group receiving either daily intraperitoneal LA (30 mg/kg) or a buffer solution for 30 days. Body weight, food intake and stool and urine collections were recorded daily. On day 30, animals were sacrificed and the carcasses, faeces and urine collected and processed for calorimetric analysis. Blood glucose and insulin were also determined. RESULTS All parameters of energy balance were affected by diabetes. LA treatment reduced weight gain, energy gain and gross food efficiency in both control and diabetic animals. However, the LA-treated animals tended to show higher energy expenditure than non-treated animals. Body composition was also affected by diabetes: fat content was impaired by LA treatment in both control and diabetic animals. The latter also showed increased glycaemia and decreased insulinaemia, but LA had no effect on these parameters. CONCLUSION Our results indicate that chronic treatment with LA aggravates energy imbalances in diabetic animals. Moreover, our data suggest the need to reconsider the use of LA as an adjuvant in the prevention and treatment of type 1 diabetes.