Aerobic Physical Exercise Improves Exercise Tolerance and Fasting Glycemia Independent of Body Weight Change in Obese Females.

Obesity is associated with increased risk of several chronic diseases and the loss of disease-free years, which has increased the focus of much research for the discovery of therapy to combat it. Under healthy conditions, women tend to store more fat in subcutaneous deposits. However, this sexual dimorphism tends to be lost in the presence of comorbidities, such as type 2 diabetes mellitus (T2DM). Aerobic physical exercise (APE) has been applied in the management of obesity, however, is still necessary to better understand the effects of APE in obese female. Thus, we investigated the effect of APE on body weight, adiposity, exercise tolerance and glucose metabolism in female ob/ob mice. Eight-weeks-old female wild-type C57BL/6J and leptin-deficient ob/ob mice (Lepob) were distributed into three groups: wild-type sedentary group (Wt; n = 6), leptin-deficient sedentary group (LepobS; n = 5) and leptin-deficient trained group (LepobT; n = 8). The LepobT mice were subjected to 8 weeks of aerobic physical exercise (APE) at 60% of the maximum velocity achieved in the running capacity test. The APE had no effect in attenuating body weight gain, and did not reduce subcutaneous and retroperitoneal white adipose tissue (SC-WAT and RP-WAT, respectively) and interscapular brown adipose tissue (iBAT) weights. The APE neither improved glucose intolerance nor insulin resistance in the LepobT group. Also, the APE did not reduce the diameter or the area of RP-WAT adipocytes, but the APE reduced the diameter and the area of SC-WAT adipocytes, which was associated with lower fasting glycemia and islet/pancreas area ratio in the LepobT group. In addition, the APE increased exercise tolerance and this response was also associated with lower fasting glycemia in the LepobT group. In conclusion, starting APE at a later age with a more severe degree of obesity did not attenuate the excessive body weight gain, however the APE promoted benefits that can improve the female health, and for this reason it should be recommended as a non-pharmacological therapy for obesity.

Potencial do treinamento físico aeróbio para minimizar os efeitos da deficiência de leptina em um modelo experimental de camundongos fêmeas / Potential of aerobic physicaltrainingto minimize the effects of leptin deficiency in an experimental model of female mice

O treinamento físico aeróbio (TFA) tem sido cada vez mais recomendado para a prevenção e tratamento de comorbidades, que podem ter em comum a resistência periférica à insulina (RI), como o diabetes tipo 2 (DM2) ea obesidade. Caracterizada pelo acúmulo excessivo de tecido adiposo, a obesidade também implica a disfunção endócrina desse tecido. Leptina e adiponectina são hormônios secretados pelos adipócitos que desempenham importante função no metabolismo energético, cujo desequilíbrio está fortemente relacionado à obesidade e à RI. Fisiologicamente, mulheres apresentam maiores níveis de leptina e adiponectina comparados aos de homens. Contudo, em condições como a obesidade e/ou DM2 esses níveis diminuem, deixando o organismo de fêmeas sem os efeitos protetores dessas adipocinas. Assim, o presente estudo teve como objetivo investigar os efeitos do TFA sobre as características morfofuncionais de TAB e pâncreas de camundongos fêmeas com deficiência de leptina. Para isso, camundongos fêmeas com oitosemanas de idade C57BL/J6 selvagem (C57) ou com deficiência de leptina ob/ob (Lepob) foram separadas nos grupos sedentárias (S) e treinadas (T): C57S (n=6), C57T (n=6), LepobS (n=5) e LepobT (n=8). O TFA foi realizadodurante oito semanas, com corrida a 60% da capacidade máxima, 1h/dia, 5x/semana. Água e ração foram administradas ad libitum. Os procedimentos foram aprovados pelo CEUA da EACH-USP (#001/2017). O acompanhamento do peso corporal e consumo de ração foi realizado semanalmente. Na 7ª semana de protocolo foram realizados os testesde tolerância àglicose (TTG) e à insulina (TTI). Ao final do protocolode treinamento foram avaliados parâmetros metabólicos de repouso e de esforço através da calorimetria indireta. A eutanásia dos animais foi realizada cominjeção intraperitoneal de anestésico e, em seguida, foram coletados os tecidos adiposos branco (TAB) subcutâneo e retroperitoneal e a porção esplênica do pâncreas, utilizados, posteriormente, para análises morfológicas. A determinação de adiponectinasérica foi realizada através de kit ELISA. Os resultados foram analisados por ANOVA de duas vias mais o teste post-hoc de Bonferroni. O protocolo de TFA não foi eficaz em reduzir a adiposidade e hiperfagia dos animais LepobS e LepobT, contudo o grupo LepobT apresentou tamanho reduzido de adipócitos doTAB-SC comparado ao grupo LepobS.O TFA não afetouo metabolismo glicêmico dos animais. Os parâmetros metabólicos derepouso não apresentaram alteração, contudo, noteste de esforço físico máximo, o grupo LepobT apresentou maiores tempo em teste até a exaustão e iVO2 comparado ao grupo LepobS. Por fim, embora o TFA não tenha aumentadoa secreção de adiponectina, o que poderia regular positivamente o metabolismo glicêmico de camundongos deficientes em leptina, melhorou a condição metabólica desses animais e reduziu a hipertrofia dos adipócitos do TAB-SC

Aerobic physical training (APT) has become an important strategy for the prevention and treatment of comorbidities, which may have in common the peripheral resistance to insulin(RI), such as type 2 diabetes and obesity. Characterized by the excessive accumulation of adipose tissue, obesity also implies endocrine dysfunction of this tissue.Leptin and adiponectin are hormones secreted by adipocytes that play an important role in energy metabolism, whose imbalance is strongly related to obesity and RI. Physiologically, women have higher levels of leptin and adiponectin compared to men.However,in conditions such as obesity and/or type 2 diabetes these levels decrease, leaving the body of females without the protective effects of these adipokines.Thus, the present study aimed to investigate the effects of APTon the morphofunctional characteristics of white adipose tissue (WAT)and pancreas in leptin-deficientfemale mice. For this, 8-week-old wild C57BL/J6 (C57) or leptin-deficient ob/ob (Lepob) female mice were separated into the groups sedentary (S) and trained (T): C57S (n = 6), C57T (n = 6), LepobS (n = 5) and LepobT (n = 8). Mice were housed in a temperature-controlled (22 ± 2°C) and 12-h light/12-h dark cycle, with free access to tap water and food ad libitum. The APT was performed for 1 h/day at 60% of maximal velocity achieved in the running capacity test, five times per week for eight weeks. The procedures were performed in accordance with the guidelines of the Brazilian College for Animal Experimentation and were approved by the Ethics Committee of the School of Arts, Sciences and Humanities of University of Sao Paulo (Process number001/2017). Body weight and feed intake were evaluated weekly. In the 7th week of protocol, the glucose and insulin tolerance tests (GTT and ITT) were performed. At the end of the training protocol, metabolic parameters of resting and maximal exertion were evaluated through indirect calorimetry. The euthanasia of the animals was performed by intraperitoneal injection of anaesthetic and thenthe subcutaneous and retroperitoneal WAT and the splenic portion of the pancreas were collected, and subsequentlyused for morphological analysis. Serum adiponectin quantification was performed by ELISA kit. The results were analyzed by two-way ANOVA plus the Bonferroni post-hoc test. The APT protocol was not effective in reducing the adiposity and hyperphagia of the animals LepobS and LepobT, however the LepobT group presented a reduced size of WAT-SC adipocytes compared to the LepobS group. Also, APT did not affectthe glycemic metabolism of theseanimals. Although the resting metabolic parameters were not different, in the maximal physical exercise test, the LepobT group had longer time to exhaustion test and iVO2 compared to the LepobS group.Finally, although APTdid not increase adiponectin plasma concentration, which could positively regulate the glycemic metabolism of leptin-deficient mice, it improved the metabolic condition of these animals and reduced the adipocyte hypertrophy of WAT-SC