Central and peripheral effects of physical exercise without weight reduction in obese and lean mice

To investigate the central (hypothalamic) and peripheral effects of exercise without body weight change in diet-induced obesity (DIO). Twelve-week-old male C57Bl/6 mice received a control (C) or a high-fat diet (H). Half of them had free access to running wheels for 5 days/week for 10 weeks (CE) and HE, respectively). Hypothalamic expression of genes related to energy homeostasis, and leptin (Stat3 and p-Stat3) and insulin (Akt and p-Akt) signaling were evaluated. Glucose and leptin tolerance, peripheral insulin sensitivity, and plasma insulin, leptin and adiponectin were determined. Perigonadal and retroperitoneal fat depots were increased by diet but reduced by exercise despite lack of effect of exercise on body weight. Blood glucose during intraperitoneal glucose tolerance test (ipGTT) was higher and glucose decay during intraperitoneal insulin tolerance test (ipITT) was lower in H and HE compared with C and CE. Exercise increased liver p-Akt expression and reduced fast glycemia. High-fat diet increased plasma insulin and leptin. Exercise had no effect on insulin but decreased leptin and increased adiponectin. Leptin inhibited food intake in all groups. Hypothalamic total and p-Stat3 and Akt were similar amongst the groups despite higher plasma levels of leptin and insulin in H and HE mice. High-fat diet modulated gene expression favoring a positive energy balance. Exercise only marginally changed the gene expression. Exercise induced positive changes (decreased fast glycemia and fat depots; increased liver insulin signaling and adiponectin concentration) without weight loss. Thus, despite reducing body weight could bring additional benefits, the effects of exercise must not be overlooked when weight reduction is not achieved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Univ Fed Sao Paulo, Programa Posgrad Interdisciplinar Ciencias Saude, Santos, SP, BrazilUniv Fed Sao Paulo, Programa Posgrad Alimentos Nutr & Saude, Santos, SP, BrazilUniv Estadual Campinas Unicamp, Inst Biol, Dept Biol Func & Estrutural, Campinas, SP, BrazilUniv Fed Sao Paulo, Inst Saude & Soc, Dept Biociencias, Santos, SP, BrazilUniv Fed Sao Paulo, Programa Posgrad Interdisciplinar Ciencias Saude, Santos, SP, BrazilUniv Fed Sao Paulo, Programa Posgrad Alimentos Nutr & Saude, Santos, SP, BrazilUniv Fed Sao Paulo, Inst Saude & Soc, Dept Biociencias, Santos, SP, BrazilFAPESP: 2011/05932-3FAPESP: 2013/01624-8Web of Scienc

Efeitos de diferentes tipos de dieta (hipoprotéica e hiperlipídica) sobre a atividade física espontânea e expressão hipotalâmica de genes relacionados à homeostase energética de camundongos

The impact of an inactive lifestyle goes beyond obesity, evidencing the importance of studying mechanisms that regulate physical activity, classified as voluntary exercise (sports, academy) and spontaneous physical activity (SPA - routine activities), which can represent more than 50% of total daily energy expenditure. Recent studies have shown that diet can affect SPA. Thus, our goal was to characterize SPA and energy expenditure (EE) in mice fed isocalorically with a low protein -LP (6% protein) or high fat- HFD (34% fat) diet for 12 weeks. Two separated studies were performed. In study 1, we evaluated the effect of a calorie matched high -fat diet (34% fat) for 12 weeks on SPA and EE of 8 weeks-old C57Bl/6 mice. Compared to control group (C), mice fed with isocaloric amount of HFD had reduced SPA all over the experiment. The energy expenditure also decreased compared to C mice, resulting in a significant increase in body weight and fat pad weight. HFD animals showed postprandial hyperglycemia, hiperinsulinemia and increased plasma concentration of IL-6. Expression of Agrp, Bdnf, Opmr1, Adra2b, Pyy and Nts genes was altered in the hypothalamus of these mice, highlighting the downregulation of BDNF, a key regulator of energy homeostasis. In study 2 ; we evaluated SPA and hypothalamic insulin signalling in weaned or adult mice fed with LP. After 12 weeks, hypothalamic insulin sensitivity was not altered in both, Weaned -LP or Adult-LP, in relation to their control groups. LP diet did not affect the overall level of SPA regardless the age the diet was initiated. However, during all the experiment, W-LP mice showed a progressively disrupted light/dark pattern of activity, which was not reproduced in the A-LP. Distance travelled and average speed was affected in the same way. In conclusion, despite calorie-matched, HFD promoted increase in weight gain and can affect energy homeostasis by decreasing SPA and consequently EE. The substantial change in hypothalamic gene expression, caused by HFD, may be behind the reduction in SPA, which plays a key role in the energy balance. On the other hand, reducing the protein content of the diet did not change the overall SPA, EE and other parameters of activity. However, when offered in the weaning, LP diet disrupts the circadian pattern of activity, which may contribute to the late metabolic disorders observed in protein restriction animals.O impacto de um estilo de vida sedentário vai além da obesidade, evidenciando a importância do estudo de mecanismos que regulam a atividade física, classificada em exercício voluntário (esportes e academia) e atividade física espontânea -spontaneous physical activity - SPA (atividades rotineiras), que pode representar mais de 50% do gasto energético total diário. Estudos têm mostrado que a dieta pode afetar a SPA. Assim, o objetivo deste trabalho foi caracterizar a SPA e o gasto energético (EE) de camundongos alimentados isocaloricamente com dieta hipoproteica, low protein - LP (6% de proteína) ou hiperlipídica, high fat diet ? HFD (34% de gordura). Para isso, 2 estudos foram realizados. No estudo 1, foi verificado o efeito da HFD, oferecida de maneira calórico equivalente, por 12 semanas, sobre a SPA e EE de camundongos C57BL/6 de 8 semanas de idade. Comparados com o grupo controle (C), animais HFD tiveram SPA reduzida durante todo o experimento. O EE também diminuiu em comparação ao grupo C, resultando em maior ganho de massa corporal e dos depósitos de gordura. Animais HFD apresentaram hiperglicemia pós-prandial, hiperinsulinemia e concentração plasmática de IL-6 aumentada. A expressão dos genes AgRP, BDNF, Opmr1, Adra2b, PYY e Nts foi alterada no hipotálamo destes animais, com destaque para a subexpressão do BDNF, regulador-chave da homeostase energética. No estudo 2, foi avaliada a SPA e a sinalização da insulina no hipotálamo de camundongos recém-desmamados (weaned) ou adultos, alimentados com dieta LP. Após 12 semanas, a sensibilidade hipotalâmica à insulina não foi alterada em ambos os grupos, Weaned-LP ou AdultLP, em relação aos seus grupos controle. A dieta LP não afetou o nível geral de SPA, independentemente da idade em que foi iniciada. Porém, dur ante todo experimento, camundongos W -LP apresentaram progressiva interrupção do padrão circadiano de atividade, o que não foi reproduzido no grupo A -LP. Distância percorrida e velocidade média, foram afetadas da mesma maneira. Em conclusão, mesmo ofertada de maneira isocalórica, a HFD promoveu aumento do ganho de peso e pode afetar a homeostase energética por diminuição da SPA e consequentemente do EE. A mudança substancial na expressão gênica hipotalâmica, causada pela HFD, pode estar por trás da redução da SPA, que tem papel chave no balanço energético. Por outro lado, a redução do teor de proteína da dieta não altera a SPA total, EE e outros parâmetros locomotores. Porém, quando oferecida no desmame, a dieta LP rompe o padrão circadiano de atividade, o que pode contribuir para os desarranjos metabólicos tardios observados em animais com restrição proteica.Dados abertos - Sucupira - Teses e dissertações (2013 a 2016