A high fat diet during adolescence in male rats negatively programs reproductive and metabolic function which is partially ameliorated by exercise

An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO 2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health

Early Overfeed-Induced Obesity Leads to Brown Adipose Tissue Hypoactivity in Rats

Background/Aims: Brown adipose tissue activation has been considered a potential anti-obesity mechanism because it is able to expend energy through thermogenesis. In contrast, white adipose tissue stores energy, contributing to obesity. We investigated whether the early programming of obesity by overfeeding during lactation changes structure of interscapular brown adipose tissue in adulthood and its effects on thermogenesis. Methods: Birth of litters was considered day 0. On day 2, litter size was adjusted to normal (9 pups) and small (3 pups) litters. On day 21, the litters were weaned. A temperature transponder was implanted underneath interscapular brown adipose tissue pads of 81-day-old animals; local temperature was measured during light and dark periods between days 87 and 90. The animals were euthanized, and tissue and blood samples were collected for further analysis. The vagus and retroperitoneal sympathetic nerve activity was recorded. Results: Small litter rats presented significant lower interscapular brown adipose tissue temperature during the light (NL 37.6°C vs. SL 37.2°C) and dark (NL 38°C vs. SL 37.6°C) periods compared to controls. Morphology of small litter brown adipose tissue showed fewer lipid droplets in the tissue center and more and larger in the periphery. The activity of vagus nerve was 19,9% greater in the small litter than in control (pConclusion: Early overfeeding programming of obesity changes the interscapular brown adipose tissue structure in adulthood, leading to local thermogenesis hypoactivity, which may contribute to obesity in adults

Peak Velocity as an Alternative Method for Training Prescription in Mice

Purpose: To compare the efficiency of an aerobic physical training program prescribed according to either velocity associated with maximum oxygen uptake (vVO2max) or peak running speed obtained during an incremental treadmill test (Vpeak_K) in mice.Methods: Twenty male Swiss mice, 60 days old, were randomly divided into two groups with 10 animals each: 1. group trained by vVO2max (GVO2), 2. group trained by Vpeak_K (GVP). After the adaptation training period, an incremental test was performed at the beginning of each week to adjust training load and to determine the amount of VO2 and VCO2 fluxes consumed, energy expenditure (EE) and run distance during the incremental test. Mice were submitted to 4 weeks of aerobic exercise training of moderate intensity (velocity referring to 70% of vVO2max and Vpeak_K) in a programmable treadmill. The sessions lasted from 30 to 40 min in the first week, to reach 60 min in the fourth week, in order to provide the mice with a moderate intensity exercise, totaling 20 training sessions.Results: Mice demonstrated increases in VO2max (ml·kg−1·min−1) (GVO2 = 49.1% and GVP = 56.2%), Vpeak_K (cm·s−1) (GVO2 = 50.9% and GVP = 22.3%), EE (ml·kg−0,75·min−1) (GVO2 = 39.9% and GVP = 51.5%), and run distance (cm) (GVO2 = 43.5% and GVP = 33.4%), after 4 weeks of aerobic training (time effect, P < 0.05); there were no differences between the groups.Conclusions: Vpeak_K, as well as vVO2max, can be adopted as an alternative test to determine the performance and correct prescription of systemized aerobic protocol training to mice

Cross-fostering reduces obesity induced by early exposure to monosodium glutamate in male rats

Maternal obesity programmes a range of metabolic disturbances for the offspring later in life. Moreover, environmental changes during the suckling period can influence offspring development. Because both periods significantly affect long-term metabolism, we aimed to study whether cross-fostering during the lactation period was sufficient to rescue a programmed obese phenotype in offspring induced by maternal obesity following monosodium L-glutamate (MSG) treatment. Obesity was induced in female Wistar rats by administering subcutaneous MSG (4 mg/g body weight) for the first 5 days of postnatal life. Control and obese female rats were mated in adulthood. The resultant pups were divided into control second generation (F2) (CTLF2), MSG-treated second generation (F2) (MSGF2), which suckled from their CTL and MSG biological dams, respectively, or CTLF2-CR, control offspring suckled by MSG dams and MSGF2-CR, MSG offspring suckled by CTL dams. At 120 days of age, fat tissue accumulation, lipid profile, hypothalamic leptin signalling, glucose tolerance, glucose-induced, and adrenergic inhibition of insulin secretion in isolated pancreatic islets were analysed. Maternal MSG-induced obesity led to an obese phenotype in male offspring, characterized by hyperinsulinaemia, hyperglycaemia, hyperleptinaemia, dyslipidaemia, and impaired leptin signalling, suggesting central leptin resistance, glucose intolerance, impaired glucose-stimulated, and adrenergic inhibition of insulin secretion. Cross-fostering normalized body weight, food intake, leptin signalling, lipid profiles, and insulinaemia, but not glucose homeostasis or insulin secretion from isolated pancreatic islets. Our findings suggest that alterations during the lactation period can mitigate the development of obesity and prevent the programming of adult diseases

Protective Effect of Metformin Against Walker 256 Tumor Growth is Not Dependent on Metabolism Improvement

Background/Aims: The objective of the current work was to test the effect of metformin on the tumor growth in rats with metabolic syndrome. Methods: We obtained pre-diabetic hyperinsulinemic rats by neonatal treatment with monosodium L-glutamate (MSG), which were chronically treated every day, from weaning to 100 day old, with dose of metformin (250 mg/kg body weight). After the end of metformin treatment, the control and MSG rats, treated or untreated with metformin, were grafted with Walker 256 carcinoma cells. Tumor weight was evaluated 14 days after cancer cell inoculation. The blood insulin, glucose levels and glucose-induced insulin secretion were evaluated. Results: Chronic metformin treatment improved the glycemic homeostasis in pre-diabetic MSG-rats, glucose intolerance, tissue insulin resistance, hyperinsulinemia and decreased the fat tissue accretion. Meanwhile, the metformin treatment did not interfere with the glucose insulinotropic effect on isolated pancreatic islets. Chronic treatment with metformin was able to decrease the Walker 256 tumor weight by 37% in control and MSG rats. The data demonstrated that the anticancer effect of metformin is not related to its role in correcting metabolism imbalances, such as hyperinsulinemia. However, in morphological assay to apoptosis, metformin treatment increased programmed cell death. Conclusion: Metformin may have a direct effect on cancer growth, and it may programs the rat organism to attenuate the growth of Walker 256 carcinoma

Efeito da redução de ninhada sobre as respostas autonômicas e metabólicas de ratos Wistar

OBJETIVO: Este estudo investigou o perfil lipídico e a atividade elétrica dos nervos parassimpático (vago superior) e simpático (localizado na região esplâncnica) de ratos obesos oriundos de ninhada reduzida. MÉTODOS: Foram pesquisados dois grupos distintos, com 12 animas cada um: ninhada padrão, padronizado em nove filhotes por ninhada, e ninhada reduzida, três filhotes por ninhada. O consumo de ração e peso corporal foi acompanhado do desmame até o final do protocolo experimental. Aos 90 dias de idade, os animais foram anestesiados com (Thiopental®) e submetidos ao registro da atividade elétrica dos nervos simpático (vago) e parassimpático (da região esplâncnica); em seguida, foram sacrificados e retiradas e pesadas as gorduras retroperitoneal e periepididimal. Amostras de sangue foram coletadas para dosagens de glicemia, insulinemia, colesterol total, triglicerídeos e lipoproteína de alta densidade colesterol. RESULTADOS: Os ratos de ninhada reduzida apresentaram aumento da ingestão alimentar, peso corporal e tecido adiposo branco, quadros de hiperglicemia, hiperinsulinemia e hipercolesterolemia, aumento dos triglicérides e redução do lipoproteína de alta densidade colesterol. CONCLUSÃO: Quanto à atividade do nervo vago, os ratos ninhada reduzida apresentaram um aumento significativo em relação aos ratos ninhada padrão, e mesmo não havendo diferença na atividade simpática, o modelo ninhada reduzida mostrou-se eficaz para indução da obesidade, dislipidemia, hipercolesterolemia, hiperinsulinemia, hiperglicemia e desequilíbrio autonômico em roedores