Aerobic physical exercise (AET) is an effective nonpharmacological therapy for diabetes. Brown adipose tissue (BAT) has been investigated as a therapeutic target due to its ability to oxidize energy substrates, to produce heat through nonshivering thermogenesis, and to secrete proteins with metabolic actions, such as fibroblast growth factor 21 (FGF21). FGF21 has a broad action and may be one of the batokines involved in diabetic cardiometabolic protection. This study investigated whether the cardiometabolic effect of AET in diabetes is mediated by BAT via FGF21. Adult male C57BL6/J mice were assigned into groups: non-diabetic sedentary (NDS, n=18), non-diabetic trained (NDT, n=12), diabetic sedentary (DS, n=17), diabetic trained (DT, n=21), and diabetic trained with interscapular BAT (iBAT) surgically removed (DTR, n=8). Diabetes was induced by high-fat and -fructose diet and intraperitoneal injection of streptozotocin (120 mg/g). AET consisted of 8-wk running session of 60 min at 60% of maximal speed, 5 days/wk. Procedures were approved by Ethics Committees from School of Arts, Science and Humanities of University of São Paulo (#001/2020). Initial body weight (BW) did not differ among groups, however NDT, DS, DT and DTR groups had lower final BW compared with NDS. BW gain in the DS, DT and DTR was lower than NDS group. The weight of retroperitoneal white adipose tissue (WAT) was lower in NDT, DT and DTR groups compared with NDS, and the DS and DT groups had lower iBAT weight compared with NDS and NDT groups. No differences were observed in the weight of periepididymal and subcutaneous WAT, gastrocnemius and soleus muscles, and cardiac chambers. Food consumption (g/animal/day) was lower in DS, DT and DTR groups compared with NDS. The DS, DT and DTR groups showed hyperglycemia, glucose intolerance and insulin resistance compared with NDS and NDT groups, however only the DS group increased fasting glucose levels post-AET compared with pre-AET values. Echocardiographic evaluation revealed that the DS group presented remodeling of ventricular diameter and volume during diastole, and impairment in ventricular relaxation, which were prevented by AET in the DT and DTR groups. No differences were observed in markers of cardiac oxidative metabolism such as citrate synthase enzyme activity and protein expression of total AMPK, p-AMPK and PGC1-α. Serum FGF21 concentration was lower in the DS, DT and DTR groups, however protein expression of FGF21, FGFR1 receptor and β-klotho co-receptor in the heart did not differ among groups. In conclusion, cardiac and metabolic adaptations induced by AET in diabetic animals were not associated with circulating FGF21 secreted by BAT nor with cardiac expression of FGF21/FGFR1/β-klotho. Sao Paulo Research Foundation (FAPESP processes 2020/15748-4 and 2020/12005-0). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Autophagy is a key regulator of cellular homeostasis and neuronal survival, particularly under adverse physiological conditions. Environmental enrichment (EE), a non-pharmacological intervention providing enhanced sensory, cognitive, and motor stimulation, may modulate autophagic processes in the brain. This systematic review aimed to synthesize preclinical findings on the effects of EE on autophagy markers in rodent models subjected to diverse adverse conditions. A literature search across PubMed, Scopus, ScienceDirect, and embase yielded eight eligible studies meeting inclusion criteria. EE was found to be generally associated with upregulation of key autophagic markers such as Beclin-1, LC3-II/LC3-I ratio, cathepsins, p62, p-TFEB, and LAMP-1 across brain regions including the cortex, hippocampus, and penumbral area. However, reductions in some markers were also observed, indicating that the modulatory effects of EE are context-dependent and may vary with disease model, brain region, or EE protocol duration. These findings suggest that EE holds promise as an adjunctive strategy to modulate autophagy and mitigate neurodegeneration, though heterogeneity in study design and outcomes warrants caution during interpretation. Further mechanistic and sex-specific studies are needed to clarify the therapeutic relevance of EE-induced autophagic modulation.

The accumulation of adipose tissue is associated with metabolic disorders, including insulin resistance, type 2 diabetes (T2D), dyslipidemia, metabolic syndrome, and cardiovascular diseases (CVD). Menopause might predispose women to increase body weight and adipose tissue, and decrease lean muscle mass. Furthermore, postmenopausal women display fat mass redistribution with greater accumulation in the visceral area mainly due to hormonal shifts that result in a higher testosterone/estradiol ratio. These effects are associated with a less favorable adipokine profile, dyslipidemia, insulin resistance, and cardiac dysfunction after menopause. Fat mass is determined by the balance between the storage of triacylglycerol (TAG) (lipogenesis) and the removal of stored TAG (lipolysis) in combination with the differentiation of new adipocytes (adipogenesis). Disturbances in adipose tissue dynamics lead to an increase in lipogenesis (hypertrophy) and/or in adipogenesis (hyperplasia) to accommodate excess energy intake. While large adipocytes are dysfunctional and have greater secretion of inflammatory adipocytokines, small adipocytes are healthier and associated with metabolic improvements. Different strategies can be used to prevent or reduce body weight gain and fat mass, as well as to maintain healthy adipose tissue; however, due to robust evidence, lifestyle interventions should be pillars in this process. This review provides a comprehensive summary of findings on the role of a balanced diet and physical exercise in improving body composition and promoting healthy adipose tissue in postmenopausal women.

Worldwide, childhood obesity cases continue to rise, and its prevalence is known to increase the risk of non-communicable diseases typically found in adults, such as cardiovascular disease and type 2 diabetes mellitus. Thus, comprehending its multiple causes to build healthier approaches and revert this scenario is urgent. Obesity development is strongly associated with high fructose intake since the excessive consumption of this highly lipogenic sugar leads to white fat accumulation and causes white adipose tissue (WAT) inflammation, oxidative stress, and dysregulated adipokine release. Unfortunately, the global consumption of fructose has increased dramatically in recent years, which is associated with the fact that fructose is not always evident to consumers, as it is commonly added as a sweetener in food and sugar-sweetened beverages (SSB). Therefore, here, we discuss the impact of excessive fructose intake on adipose tissue biology, its contribution to childhood obesity, and current strategies for reducing high fructose and/or free sugar intake. To achieve such reductions, we conclude that it is important that the population has access to reliable information about food ingredients via food labels. Consumers also need scientific education to understand potential health risks to themselves and their children.

Introduction: Obesity is a major risk factor associated with multiple pathological conditions including diabetes and cardiovascular disease. Endothelial dysfunction is an early predictor of obesity. However, little is known regarding how early endothelial changes trigger obesity. In the present work we report a novel endothelial-mediated mechanism essential for regulation of metabolic homeostasis, driven by c-Myc.Methods: We used conditional knockout (EC-Myc KO) and overexpression (EC-Myc OE) mouse models to investigate the endothelial-specific role of c-Myc in metabolic homeostasis during aging and high-fat diet exposure. Body weight and metabolic parameters were collected over time and tissue samples collected at endpoint for biochemical, pathology and RNA-sequencing analysis. Animals exposed to high-fat diet were also evaluated for cardiac dysfunction.Results: In the present study we demonstrate that EC-Myc KO triggers endothelial dysfunction, which precedes progressive increase in body weight during aging, under normal dietary conditions. At endpoint, EC-Myc KO animals showed significant increase in white adipose tissue mass relative to control littermates, which was associated with sex-specific changes in whole body metabolism and increase in systemic leptin. Overexpression of endothelial c-Myc attenuated diet-induced obesity and visceral fat accumulation and prevented the development of glucose intolerance and cardiac dysfunction. Transcriptome analysis of skeletal muscle suggests that the protective effects promoted by endothelial c-Myc overexpression are associated with the expression of genes known to increase weight loss, energy expenditure and glucose tolerance.Conclusion: Our results show a novel important role for endothelial c-Myc in regulating metabolic homeostasis and suggests its potential targeting in preventing obesity and associated complications such as diabetes type-2 and cardiovascular dysfunction.

The ability of brown adipose tissue (BAT) and aerobic physical exercise (AET) to improve energy metabolism is widely known. Since AET has been used as an insulin- sensitizing therapy for diabetes, here we tested whether the effects of AET on the glycemic metabolism and aerobic capacity of diabetic animals are accompanied by structural changes in BAT. Adult male C57BL6/J mice were assigned into groups: non-diabetic sedentary (NDS, n=6), non-diabetic trained (NDT, n=6), diabetic sedentary (DS, n=4) and diabetic trained (DT, n=7). Diabetes was induced by high-fat and -fructose diet and intraperitoneal injection of streptozotocin (120 mg/g). AET consisted of 8-wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committees from Faculty of Medicine and from School of Arts, Science and Humanities of University of São Paulo (#1473/2020 and #001/2020, respectively). Initial body weight (BW) did not differ among groups, however the DS and DT groups had lower final BW compared with NDS. The BW gain of DS group was lower compared with NDS group. Food consumption (Kcal/animal/day) was higher in DT group compared with NDS and NDT. The DS and DT groups had higher fasting blood glucose, and DS group had greater area under the curve on the glucose tolerance test than the NDS and NDT groups. Indirect calorimetry measurement at rest revealed no difference in the variables oxygen uptake (VO2), carbon dioxide expiration (VCO2), respiratory exchange ratio (RER), energy expenditure (EE), carbohydrate and fat oxidation among groups. During maximal exercise test, NDT and DT increased the time to exhaustion, maximal speed, intensity corresponding to the VO2máx (iVO2) compared with NDS and DS. An increase in VO2máx and VCO2máx was observed in NDT group compared with DS and DT group. No differences were observed in the weight of white adipose tissue depots (retroperitoneal, periepididymal and subcutaneous), interscapular brown adipose tissue (iBAT), skeletal muscle (gastrocnemius and soleus), and other organs (heart, lung, and kidney). Morphometric analysis of the iBAT revealed that the area, diameter, volume, mass, frequency of lipid droplet distribution by size (small, medium, large, and very large) and amount of lipid droplets did not differ among groups, however, collagen deposition in the iBAT increased in the DS and DT groups compared with NDS group. In conclusion, the AET-induced improvement in glucose tolerance and aerobic capacity in diabetic animals is not accompanied by changes in morphometry and collagen deposition in the iBAT. This study was supported by grants from the São Paulo Research Foundation (FAPESP) #2020/15748-4 and #2020/12005-0. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

We tested the hypothesis that third ventricular (3V) injections of angiotensin 1-7 (Ang 1-7) increases thermogenesis in brown adipose tissue (BAT), and whether the Mas receptor mediates this response. First, in male Siberian hamsters (n = 18), we evaluated the effect of Ang 1-7 in the interscapular BAT (IBAT) temperature and, using selective Mas receptor antagonist A-779, the role of Mas receptor in this response. Each animal received 3V injections (200 nL), with 48 h intervals: saline; Ang 1-7 (0.03, 0.3, 3, and 30 nmol); A-779 (3 nmol); and Ang 1-7 (0.3 nmol) + A-779 (3 nmol). IBAT temperature increased after 0.3 nmol Ang 1-7 compared with Ang 1-7 + A-779 at 20, 30, and 60 min. Also, 0.3 nmol Ang 1-7 increased IBAT temperature at 10 and 20 min, and decreased at 60 min compared with pretreatment. IBAT temperature decreased after A-779 at 60 min and after Ang 1-7 + A-779 at 30 and 60 min compared with the respective pretreatment. A-779 and Ang 1-7 + A-779 decreased core temperature at 60 min compared with 10 min. Then, we evaluated blood and tissue Ang 1-7 levels, and the expression of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) in IBAT. Male Siberian hamsters (n = 36) were killed 10 min after one of the injections. No changes were observed in blood glucose, serum and IBAT Ang 1-7 levels, and ATGL. Ang 1-7 (0.3 nmol) increased p-HSL expression compared with A-779 and increased p-HSL/HSL ration compared with other injections. Ang 1-7 and Mas receptor immunoreactive cells were found in brain regions that coincide with the sympathetic nerves outflow to BAT. In conclusion, 3V injection of Ang 1-7 induced thermogenesis in IBAT in a Mas receptor-dependent manner.

Background: Obesity is a worldwide concern due to its global rapid expansion and remarkable impact on individual’s health by predisposing to several other diseases. About twice as many women as men suffer from severe obesity and, in fact, there are stages in a woman’s life when weight gain and adiposity can result in greater damage to health. For example, obesity triples the chance of a woman developing gestational diabetes. Many hormones promote the metabolic adaptations of pregnancy, including progesterone, whose role in female obesity is still not well known despite being involved in many physiological and pathological processes. Methods: Here we investigated whether progesterone treatment at low dose can worsen the glucose metabolism and the morpho functional aspects of adipose tissue and pancreas in obese females. Mice were assigned into four groups: normocaloric diet control (NO-CO), high-fat and -fructose diet control (HFF-CO), normocaloric diet plus progesterone (NO-PG) and high-fat and -fructose diet plus progesterone (HFF-PG) for 10 weeks. Infusion of progesterone (0.25 mg/kg/day) was done by osmotic minipump in the last 21 days of protocol. Results: Animals fed a hypercaloric diet exhibited obesity with increased body weight (p < 0.0001), adipocyte hypertrophy (p < 0.0001), hyperglycemia (p = 0.03), and glucose intolerance (p = 0.001). HFF-CO and HFF-PG groups showed lower adiponectin concentration (p < 0.0001) and glucose-stimulated insulin secretion (p = 0.03), without differences in islet size. Progesterone attenuated glucose intolerance in the HFF-PG group (p = 0.03), however, did not change morphology or endocrine function of adipose tissue and pancreatic islets. Conclusions: Taken together, our results showed that low dose of progesterone does not worsen the effects of hypercaloric diet in glycemic metabolism, morphology and function of adipose tissue and pancreatic islets in female animals. These results may improve the understanding of the mechanisms underlying the pathogenesis of obesity in women and eventually open new avenues for therapeutic strategies and better comprehension of the interactions between progesterone effects and obesity.

Fibroblast growth factor 21 (FGF-21) is a protein that is involved in the regulation of glucose, lipids, and energy metabolism. To act on target tissues, endocrine FGF-21 binds preferably to FGF receptor 1 (FGFR1) in the presence of the coreceptor named β-klotho (KLB). Some of the effects of FGF-21 include increased fatty acid oxidation, glucose uptake, insulin sensitivity, and thermogenesis, which can regulate body weight and glycemia control. By exerting such metabolic effects, the therapeutic potential of FGF-21 for the treatment of obesity and diabetes has been investigated. Physical exercise has been widely used for the prevention and treatment of obesity. Several mechanisms mediate the effects of physical exercise, including the FGF-21 pathway. Studies have shown that physical exercise increases the concentration of circulating and tissue FGF-21 in animals, while contradictory results are still observed in humans. Considering the metabolic role of FGF-21 and the chance of physical exercise to induce FGF-21 secretion, in this review we explore the potential of physical exercise-induced FGF-21 modulation as a strategy for prevention and treatment of obesity.

Increased energy expenditure influences lipid handling by the liver. Aerobic exercise training (AET) has been widely used for the prevention and treatment of liver disorders especially non-alcoholic fatty liver disease (NAFLD). In the present study, we evaluated the contribution of visceral white and brown adipose tissue (WAT and BAT, respectively) and the skeletal muscle to prevent NAFLD through aerobic physical exercise (APE). Adult male C57BL6/J mice were assigned into groups (n=10/group): chow-fed controls (C), chow-fed trained (T), cafeteria diet (CAF), and cafeteria diet and trained (CAFT). AET was performed simultaneously with diet and consisted of 8-wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from Faculty of Medicine of University of São Paulo (002/2015) and from School of Arts, Science and Humanities, University of Sao Paulo (002/2018). The CAF group presented higher body weight gain, glucose intolerance, insulin resistance while AET prevented such damages in the CAFT group. In the liver, lipid deposition was higher in CAF (10.7 ± 1.9 %/area) compared to C, T and CAFT groups (6.4 ± 1.4, 0.5 ± 0.2 and 5.3 ± 1.1 %/area, respectively), the protein expression of DGAT2 did not differ but the expression of FAS enzyme and the content of IL-6 was lower in CAFT compared to CAF. The CAF group increased periepididymal WAT weight compared to C and T groups, and the protein expressions of p-HSL and ATGL, which are markers of lipolysis, increased in both CAF and CAFT compared to C and T groups. In addition, interscapular BAT weight did not change among groups, however the protein expression of UCP1 and PGC1a, which are markers of thermogenesis, increased in both CAF and CAFT compared to C and T groups. The activity of oxidative enzymes citrate synthase and β-HAD in the soleus muscle increased in the T (352 ± 21.5 and 80.1 ± 6.6 mmol/min/mg) and CAFT (350 ± 22.4 and 87.9 ± 7.3 mmol/min/mg) groups compared to C (272.7 ± 9.5 and 62.7 ± 3.9 mmol/min/mg) and CAF (254.6 ± 15.7 and 46.7 ± 1.6 mmol/min/mg) groups. In conclusion, for the prevention of NAFLD, the AET increased the metabolic activation of WAT and BAT that favors fat oxidation as well as improved the oxidative capacity of skeletal muscle to deal with excess lipids.

Obesity is mainly caused by excess energy intake and physical inactivity, and the number of overweight/obese individuals has been steadily increasing for decades. Previous studies showed that rodents fed westernized diets exhibit endocrine pancreas deterioration and a range of metabolic disorders. This study evaluated the effects of moderated aerobic treadmill exercise training on pancreatic islet cell viability and function in mice consuming a high-fat and sucrose diet. In the present study, 60-day-old male C57BL/6J mice were divided into four groups: control (C), fed a standard diet AIN-93M (3.83 kcal/g; 70% carbohydrate (cornstarch and dextrinized starch were chosen as the major source of carbohydrate for the AIN-93 diet. In addition, a small amount of sucrose), 20% protein (casein), and 10% fat (soybean) with no training (i.e., sedentary); C + training (CTR, fed the standard diet with eight weeks of exercise; high-fat diet + sucrose (HFDS), fed a high fat and sucrose diet (5.2 kcal/g; 20% carbohydrate (cornstarch and dextrinized starch were chosen as the major source of carbohydrate), 20% protein (casein), 60% fat (Lard was chosen as the major source of fat and a small amount of soybean) + 20% sucrose diluted in drinking water with no training; and HFDS + training (HFDSTR). After eight weeks, the HFDS mice displayed increased body weight (P<0.001) and epididymal, inguinal and retroperitoneal adipose tissue mass (P<0.01). These mice also presented insulin resistance (P<0.01), glucose intolerance (P<0.001), impaired glucose-stimulated insulin secretion (GSIS) and were less responsive to the physiological net ROS production induced by glucose stimulus. The HFDS group’s pancreatic islet cells were 38% less viable and 59% more apoptotic than those from the C group (P<0.05). The HFDSTR improved glucose tolerance, body mass, insulin sensitivity and GSIS (P<0.05). Furthermore, HFDSTR mice had 53% more viable isolated pancreatic islets cells and 29% fewer apoptotic cells than the HFDS group (P<0.01). Thus, exercise training may slow down and/or prevent adverse metabolic effects associated with consuming a westernized diet.

Since the incidence of gestational diabetes is higher in obese women and those treated with progestogens during pregnancy, the aim of this study was to investigate the effect of progesterone (PG) on body composition, glucose metabolism and metabolic parameters in obese female mice. Post-weaned female C57Bl/J6 were distributed into four groups: normocaloric control (NO-CO, n=11), high fat and fructose control (HFF-CO, n=10), normocaloric PG (NO-PG, n=8) and high fat and fructose PG (HFF-PG, n=9). The NO-CO and NO-PG mice fed a AING93 standard diet and the HFF-CO and HFF-PG fed a AIN93G diet added of lard (31%) and fructose (24%) during 10 weeks. In the 7th week, NO-PG and HFF-PG received an osmotic pump implant for constant infusion (0,25 mg/kg/d) of PG. All procedures were approved by the Ethics Committee of the School of Arts, Sciences and Humanities of University of Sao Paulo (003/2018). The daily food intake in grams was similar in all groups, but in terms of calories, the intake of the HFF-CO and HFF-PG (13.24+0.9 and 13.06+0.72 kcal/animal) groups was higher than NO-CO and NO-PG (9.22+0.2 and 9.53+0.53 kcal/animal) groups. The body weight gain was greater the HFF-CO and HFF-PG (11.52+0.94 and 9.61+0.85 g) groups compared to NO-CO and NO-PG (5.85+0.51 and 5.69+0.5 g) groups. Considering the final body weight of these animals (NO-CO, 22.14+0.34 g; NO-PG, 21.89+0.33 g; HFF-CO, 28.76+0.59 g; HFF-PG, 26.27+0.67 g) we observed not only the predicted increase in the weight of groups that received the HFF-CO diet but also a lower increase in HFF-PG group compared to HFF-CO group. White adipose tissue fat pads (subcutaneous, SC-WAT and retroperitoneal, RP-WAT) increased significantly in the HFF-CO group compared to NO-CO and PG groups. In HFF-PG, both WAT fat pads were greater compared to NO-PG group, but only the WAT-RP was greater compared to NO-CO group. No differences were observed in interscapular brown adipose tissue and pancreas weight. On the other hand, the weight of liver was lower in HFF and HFF-PG compared to NO-CO and PG groups. No difference was found in the fasting glycaemia in the animals. From the results of the GTT and area under the curve (AUC) we observed that the HFF (23907+1304 mg/dL/120min) presented significantly higher AUC than NO-CO and NO-PG (17327+1042 and 18096+989 mg/dL/120min) groups. In addition, kITT of HFF-CO (2.86+0.26 %/min) was significantly smaller compared to NO-CO (4.23+0.56 %/min), NO-PG (4.07+0.64 %/min) and HFF-PG (3.89+0.4 %/min). Metabolic parameters measured in the indirect calorimetry during resting such as resting oxygen consumption, energy expenditure, respiratory exchange ratio, and the rates of carbohydrate and lipids oxidation did not differ among groups. In conclusion, the treatment with PG in a concentration that mimics those found in pregnancy attenuated body weight gain, adiposity and glycaemic metabolism damage observed in obese female mice.

Type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) are among the top ten causes of death in the world.It is observed that the association between T2DM and cardiovascular risk is not the same for both sexes, with cardiovascular risk associated with T2DM being greater in women.Among the different strategies for the prevention and treatment of T2DM and risk factors for CVD, the physical exercise has been largely recommended because of positive effects for the glycemic control, body mass, blood pressure, and lipid profile.Therefore, this manuscript aimed to review the literature about the risk factors that connect T2DM to CVD, the benefits of different types of physical exercise on these factors, and the differences between women and men in this context.The research was carried out in PubMed and Web of Science databases to find works that highlighted the differences between women and men on risk factors that connect T2DM to CVD and the effects of physical exercise.The most recent works, seminal and/or with the closest relationship with T2DM were selected to review.Some different responses were identified between the sexes, although it was not possible to identify whether such differences are due to the characteristics of the sexes or the absence of specific physical exercise protocols for women.In any case, this review reaffirms the benefits of physical exercise for the control of risk factors that connect T2DM and CVD, both in women and in men, and the need for further studies that consider the differences between sexes and so they can propose increasingly adequate protocols.

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.

Abstract Background We investigate the effect of aerobic physical training (APT) on muscle morphofunctional markers and Angiotensin Converting Enzyme 2/Angiotensin 1-7/Mas receptor (ACE2/Ang 1-7/Mas) axis in an obesity-linked insulin resistance (IR) animal model induced by cafeteria diet (CAF). Methods Male C57BL/6J mice were assigned into groups CHOW-SED (chow diet, sedentary; n = 10), CHOW-TR (chow diet, trained; n = 10), CAF-SED (n = 10) and CAF-TR (n = 10). APT consisted in running sessions of 60 min at 60% of maximal speed, 5 days per week for 8 weeks. Results Trained groups had lower body weight and adiposity compared with sedentary groups. CAF-TR improved the glucose and insulin tolerance tests compared with CAF-SED group (AUC = 28.896 ± 1589 vs. 35.200 ± 1076 mg dL−1 120 min−1; kITT = 4.1 ± 0.27 vs. 2.5 ± 0.28% min−1, respectively). CHOW-TR and CAF-TR groups increased exercise tolerance, running intensity at which VO2 max was reached, the expression of p-AMPK, p-ACC and PGC1-α proteins compared with CHOW-SED and CAF-SED. Mithocondrial protein expression of Mfn1, Mfn2 and Drp1 did not change. Lipid deposition reduced in CAF-TR compared with CAF-SED group (3.71 vs. 5.53%/area), but fiber typing, glycogen content, ACE2 activity, Ang 1-7 concentration and Mas receptor expression did not change. Conclusions The APT prevents obesity-linked IR by modifying the skeletal muscle phenotype to one more oxidative independent of changes in the muscle ACE2/Ang 1-7/Mas axis.

Recent reports have shown that the renin angiotensin system (RAS) plays an important role in the Coronavirus disease 2019 (COVID-19) because the angiotensin converting enzyme 2 is the receptor for the severe acute respiratory syndrome coronavirus 2. In addition, the balance of RAS components can be involved in the pathogenesis and progression of COVID-19, especially in patients with metabolic and cardiovascular diseases. On the other hand, physical exercise is effective to prevent and to counteract the consequences of such diseases and one of the biological mediators of the exercise adaptation is the RAS. This review was designed to highlight the connection between COVID-19 and RAS, and to discuss the role of the RAS as a mediator of the benefits of physical exercise in COVID-19 pandemic.

Aerobic exercise training (AET) has been widely used for the prevention and treatment of obesity and insulin resistance (IR). Improvements in the oxidative capacity of skeletal muscle can mediate the protective effect of AET. Considering the role of angiotensin converting enzyme 2 (ACE2)/angiotensin 1‐7 (Ang 1‐7)/receptor Mas axis activation in reducing cardiometabolic diseases, the present study aimed to evaluate if the prevention of obesity and IR through AET is associated with changes in the ACE2/Ang (1‐7)/Mas axis in the skeletal muscle. Adult male C57BL6/J mice were assigned into groups (n=10/group): chow‐fed controls (C), chow‐fed trained (T), cafeteria diet (CAF), and cafeteria diet and trained (CAFT). AET was performed simultaneously with diet and consisted of 8‐wk running session of 60 min at 60% of maximal speed, 5 days/wk. Experimental procedures were approved by Ethics Committee from School of Arts, Science and Humanities, University of Sao Paulo, Brazil (#001/2016). The CAF group presented higher body weight gain and adiposity, glucose intolerance, IR and increased lipid deposition in the liver while AET prevented such damages in the CAFT group. Food consumption did not change among the groups. During the maximal physical exertion test, the T group increased VO2máx and both T and CAFT groups showed higher maximal speed, higher speed on the VO2máx and lower relative running cost compared to C and CAF groups. The enzymatic activity of citrate synthase and β‐hydroxyacyl‐CoA dehydrogenase (β‐HAD) in the soleus muscle increased in the T (352 ± 21.5 mmol/min/mg and 80.1 ± 6.6 mmol/min/mg) and CAFT (350 ± 22.4 mmol/min/mg and 87.9 ± 7.3 mmol/min/mg) groups compared to C (272.7 ± 9.5 mmol/min/mg and 62.7 ± 3.9 mmol/min/mg) and CAF (254.6 ± 15.7 mmol/min/mg and 46.7 ± 1.6 mmol/min/mg) groups. Protein expression of mitofusin 1, mitofusin 2 and dynamin related protein 1 (Drp1) did not change among groups. Also, no differences were observed in the ACE2 and Ang (1‐7) levels nor in the receptor Mas protein expression. In conclusion, the AET prevented the increase in body weight, adiposity and IR induced by cafeteria diet, improved the aerobic capacity and promoted the increase in oxidative enzymes activity in the soleus muscle. However, the adaptations induced by AET were not associated with changes in the ACE2/Ang (1‐7)/Mas axis in the skeletal muscle.Support or Funding InformationSão Paulo Research Foundation (FAPESP #2015/04948‐4; #2016/23783‐9; #2016/20659‐5).

Purpose: To evaluate the effect of 8 weeks of aerobic training on insulin resistance and inflammatory response in obese mice (ob/ob) with NAFLD. Materials and Methods: Male ob/ob mice were randomly divided into sedentary (n=7) and trained (n=7) groups. Aerobic training consisted of 5 weekly sessions, 60 min per session at 60% of the maximum speed of the running test. Hepatic and pancreatic samples were collected to evaluate histological features and gene expression associated with insulin resistance and inflammatory response after 8-week experiment protocol. RNA was performed by TRIzol (R). PCR experiments were performed using the Rotor-Gene RG-3000. Parametric data were assessed by t-test, one-way ANOVA and Bonferroni test for multiple comparisons. Non-parametric data were assessed by the Mann-Whitney tests with Dunn's post-test of multiple comparisons. Histological analysis was assessed by chi-square test with Fisher's exact test. Significant variables were considered when p<0.05. All the analyses were performed by GraphPad Prism V6.0 software (GraphPad Software Inc.). Results: Reductions in bodyweight (p = 0.008), weight evolution (p = 0.03), food intake (p <0.0001) and fat content were observed in trained group. Moreover, the trained group showed better results in peak velocity (p=0.03) physical effort tolerance (p=0.006) and distance (p=0.01). Gene expression showed differences in IL-10 (p=0.03) and GLUT-2 (p=0.03) in hepatic analysis, between groups. Pancreatic gene expression showed difference between groups in IRS-2 (p=0.004), GLUT-2 (p=0.03) and IL-10 (p=0.008) analysis. Also, the trained group showed lower values for interlobular fat and inflammatory infiltrate in histological analysis when compared to sedentary animals. Conclusion: An 8-week physical training protocol was able to attenuate bodyweight gain, food intake and generate positive effects on gene expression related to insulin resistance and inflammation in both liver and pancreas of ob/ob mice.

Recent reports have shown that the renin angiotensin system (RAS) plays an important role in the Coronavirus disease 2019 (COVID-19) because the angiotensin converting enzyme 2 is the receptor for the severe acute respiratory syndrome coronavirus 2. In addition, the balance of RAS components can be involved in the pathogenesis and progression of COVID-19, especially in patients with metabolic and cardiovascular diseases. On the other hand, physical exercise is effective to prevent and to counteract the consequences of such diseases and one of the biological mediators of the exercise adaptation is the RAS. This review was designed to highlight the connection between COVID-19 and RAS, and to discuss the role of the RAS as a mediator of the benefits of physical exercise in COVID-19 pandemic.

Aerobic physical training (APT) is an important strategy for prevention and treatment of comorbidities such as type 2 diabetes and obesity. Leptin and adiponectin play an important role in energy metabolism, whose imbalance is strongly related to obesity and insulin resistance (IR). Although women have higher levels of leptin and adiponectin compared to men, in conditions such as obesity and/or type 2 diabetes these levels decrease, abolishing the protective effects of these adipokines in females. This study investigated the effects of APT on the metabolic parameters in leptin‐deficient female 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) (C57S, n = 6 and LepobS, n = 5) and trained (T) (LepobT, n = 8). The APT was performed during 1 h/day at 60% of maximal speed achieved in the maximal physical exertion test, 5 times/week for eight weeks. The procedures were approved by the Ethics Committee of the School of Arts, Sciences and Humanities of University of Sao Paulo (#001/2017). LepobS and LepobT groups increased body weight, the weight of retroperitoneal (WAT‐RP) and subcutaneous (WAT‐SC) fat pads compared to C57S. Adipocyte area and diameter of WAT‐RP and WAT‐SC were higher in both LepobS and LepobT compared to C57S, however the APT decreased the WAT‐SC adipocyte area and diameter in LepobT group compared to LepobS. LepobS and LepobT groups showed lower weight of pancreas, gastrocnemius and plantar muscles compared to C57S, however APT prevented the mass reduction of gastrocnemius and plantar muscles in LepobT. Food intake was higher in LepobS compared to C57S, which was counteracted by APT in the LepobT group. The LepobS had fasting hyperglycemia (131 ± 1.02 mg/dL) and glucose intolerance (AUC: 31522 ± 1148 mg/dL/120min) compared to C57S (92 ± 2.51 mg/dL and AUC: 20339 ± 1857 mg/dL/120min). Despite of LepobT group had shown glucose intolerance (AUC: 30085 ± 547 mg/dL/120min), the APT decreased the fasting glycemia (114 ± 6.11 mg/dL) compared to LepobS group. Adiponectin level did not change among groups, as well as the relative area of islets in the pancreatic tissue. During the maximal physical exertion test, LepobT showed higher maximal speed, time to exhaustion and speed on the VO2máx compared to LepobS group. In conclusion, APT prevented the loss of gastrocnemius and plantar muscles mass, reduced WAT‐SC adipocyte hypertrophy and food intake, improved fasting glycemia and aerobic capacity in leptin deficient female mice.Support or Funding InformationFAPESP (#2018/22361‐9), CAPES, CNPq