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It is of great importance to investigate the effects of physical exercise for metabolic health when performed in early life, and what the adulthood response would be. The aim of this study is to analyse the effects of moderate intensity physical exercise protocol during childhood on the adipose tissue and insulin sensitivity of rats during adulthood. Twenty weaned Wistar (28 days old) were divided into control and trained groups. The Control Group was kept sedentary, and the Trained group was submitted to swimming exercise at 80% of the anaerobic threshold (determined by the lactate minimum test) for 1 hour/day, 5 days/week from 28 to 90 days of age. At the end of the experiment, the body weight, adiposity (adipose tissue weight), insulin sensitivity, glycemia, insulinemia, pancreatic insulin, lipogenic activity in mesenteric fat, lipogenic activity and glycogen store in gastrocnemius and glucose uptake by soleus were analyzed. Trained group showed lower body weight gain, fat acumulation, lipid synthesis, glycemia, insulinemia and pancreatic insulin level. Kitt, HOMA-IR, glycogen store in gastrocnemius and glucose uptake by soleus were higher in this group. Therefore, we conclude that the moderate physical exercise performed during childhood can contribute to the reduction of body fat and insulin resistance during adulthood in Wistar rats. É de grande importância a investigação dos efeitos do exercício para a saúde metabólica quando realizado no início da vida, e quais seriam as respostas durante a fase adulta. O objetivo desse estudo é analisar os efeitos do exercício físico de intensidade moderada durante a infância na adiposidade e sensibilidade à insulina de ratos durante a fase adulta. Vinte ratos Wistar desmamados de 28 dias de vida foram divididos em grupos Controle e Treinado. O grupo Controle permaneceu sedentário, enquanto o grupo Treinado realizou exercício de natação a 80% do limiar anaeróbio (determinado pelo teste de lactato mínimo) por 1hora/dia, 5dias/semana do 28º até o 90º dia de vida. No fim do experimento, a massa corporal, adiposidade, sensibilidade à insulina, glicemia, insulinemia, insulina pancreática, atividade lipogênica do tecido adiposo mesentérico, atividade lipogênica e estoques de glicogênio no músculo gastrocnêmio e captação de glicose pelo músculo sóleo foram analizadas. O grupo Treinado apresentou menor ganho de massa corporal, acúmulo de gordura, síntese de lipídios, glicemia, insulinemia e insulina pancreática. Kitt, HOMA-IR, estoques de glicogênio no gastrocnêmio e captação de glicose pelo sóleo foram maiores nesse grupo. Portanto, concluímos que o exercício físico moderado realizado durante a infância pode contribuir para a redução da adiposidade corporal e resistência à insulina durante a fase adulta em ratos Wistar.

Obesity is a chronic, non-transmissible and multifactorial disease commonly associated with systemic inflammation and damage to health. This disorder has been pointed out as leading to the development of a diversity of eye diseases and, consequently, damage to visual acuity. More specifically, cardiometabolic risk is associated with lacrimal gland dysfunctions, since it changes the inflammatory profile favoring the development and worsening of dry eye disease. In more severe and extreme cases, obesity, inflammation, and diabetes mellitus type 2 can trigger the total loss of vision. In this scenario, besides its numerous metabolic functions, clusterin, an apolipoprotein, has been described as protective to the ocular surface through the seal mechanism. Thus, the current review aimed to explain the role of clusterin in dry eye disease that can be triggered by obesity and diabetes.

Obesity is a chronic, non-transmissible and multifactorial disease commonly associated with systemic inflammation and damage to health. This disorder has been pointed out as leading to the development of a diversity of eye diseases and, consequently, damage to visual acuity. More specifically, cardiometabolic risk is associated with lacrimal gland dysfunctions, since it changes the inflammatory profile favoring the development and worsening of dry eye disease. In more severe and extreme cases, obesity, inflammation, and diabetes mellitus type 2 can trigger the total loss of vision. In this scenario, besides its numerous metabolic functions, clusterin, an apolipoprotein, has been described as protective to the ocular surface through the seal mechanism. Thus, the current review aimed to explain the role of clusterin in dry eye disease that can be triggered by obesity and diabetes.

Obesity is a disease characterized by the exacerbated increase of adipose tissue. A possible way to decrease the harmful effects of excessive adipose tissue is to increase the thermogenesis process, to the greater energy expenditure generated by the increase in heat in the body. In adipose tissue, the thermogenesis process is the result of an increase in mitochondrial work, having as substrate H+ ions, and which is related to the increased activity of UCP1. Evidence shows that stress is responsible for increasing the greater induction of UCP1 expression via β-adrenergic receptors. It is known that physical exercise is an important implement for sympathetic stimulation promoting communication between norepinephrine/epinephrine with membrane receptors. Thus, the present study investigates the influence of short-term strength training (STST) on fatty acid composition, lipolysis, lipogenesis, and browning processes in the subcutaneous adipose tissue (sWAT) of obese mice. For this, Swiss mice were divided into three groups: lean control, obesity sedentary, and obese strength training (OBexT). Obese animals were fed a high-fat diet for 14 weeks. Trained obese animals were submitted to 7 days of strength exercise. It was demonstrated that STST sessions were able to reduce fasting glycemia. In the sWAT, the STST was able to decrease the levels of the long-chain fatty acids profile, saturated fatty acid, and palmitic fatty acid (C16:0). Moreover, it was showed that STST did not increase protein levels responsible for lipolysis, the ATGL, ABHD5, pPLIN1, and pHSL. On the other hand, the exercise protocol decreased the expression of the lipogenic enzyme SCD1. Finally, our study demonstrated that the STST increased browning process-related genes such as PGC-1α, PRDM16, and UCP1 in the sWAT. Interestingly, all these biomolecular mechanisms have been observed independently of changes in body weight. Therefore, it is concluded that short-term strength exercise can be an effective strategy to initiate morphological changes in sWAT.

Made available in DSpace on 2020-12-10T20:07:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-31 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The impairment of mitochondrial metabolism is a hallmark of aging. Mitonuclear imbalance and the mitochondrial unfolded protein response (UPRmt) are two conserved mitochondrial mechanisms that play critical roles in ensuring mitochondrial proteostasis and function. Here, we combined bioinformatics, physiological, and molecular analyses to examine the role of mitonuclear imbalance and UPRmt in the skeletal muscle of aged rodents and humans. The analysis of transcripts from the skeletal muscle of aged humans (60-70 years old) revealed that individuals with higher levels of UPRmt-related genes displayed a consistent increase in several mitochondrial-related genes, including the OXPHOS-associated genes. Interestingly, high-intensity interval training (HIIT) was effective in stimulating the mitonuclear imbalance and UPRmt in the skeletal muscle of aged mice. Furthermore, these results were accompanied by higher levels of several mitochondrial markers and improvements in physiological parameters and physical performance. These data indicate that the maintenance or stimulation of the mitonuclear imbalance and UPRmt in the skeletal muscle could ensure mitochondrial proteostasis during aging, revealing new insights into targeting mitochondrial metabolism by using physical exercise. Univ Estadual Campinas, Lab Mol Biol Exercise, Limeira, SP, Brazil Sao Paulo State Univ, Inst Biosci, Dept Phys Educ, Rio Claro, SP, Brazil Univ Estadual Campinas, Lab Funct Properties Foods, Limeira, SP, Brazil Univ Sao Paulo, Postgrad Program Rehabil & Funct Performance, Ribeirao Preto, SP, Brazil Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, SP, Brazil Univ Estadual Campinas, Lab Nutr Genom, Limeira, SP, Brazil Univ Campinas UNICAMP, CEPECE Ctr Res Sport Sci, Sch Appl Sci, Limeira, SP, Brazil Univ Campinas UNICAMP, Fac Med Sci, Dept Internal Med, Campinas, SP, Brazil Sao Paulo State Univ, Inst Biosci, Dept Phys Educ, Rio Claro, SP, Brazil CNPq: 304771/2017-1 CNPq: 401189/2016-3 CAPES: 001 FAPESP: 2011/09656-0 FAPESP: 2018/07634-9

Made available in DSpace on 2018-12-11T16:55:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-10-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Aims: The aim of this study was to evaluate the effects of aging on intracellular adiponectin signaling and the possible therapeutic effect of physical exercise. Main methods: Fischer 344 rats were distributed in the following groups: Young (3 months old); Sedentary Old (Old, 27 months old); and Old Exercised (Old-Exe, 27 months old), which were subjected to a short-term exercise training protocol. Key findings: The results showed that the old rats presented glucose intolerance without increased adiposity. However, short-term exercise training reversed this disorder, which was associated with a decrease in the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif (APPL) isoform 2 (APPL2) content. The APPL isoform 1 (APPL1) and TRB3 (Tribbles homolog 3) contents were not altered. Akt phosphorylation was only increased in the old exercised rats. There was a reduction in the content of adiponectin receptor 1 in the old rats. Significance: The short-term exercise training protocol was able to decrease APPL2 content in the skeletal muscle, which was accompanied by an improvement in the glucose tolerance of the old Fischer 344 rats. These findings provide new evidence supporting the role of physical exercise as a non-pharmacological therapeutic intervention to attenuate age-related deficits. Laboratory of Molecular Biology of Exercise (LaBMEx) School of Applied Sciences University of Campinas (UNICAMP) Post-graduate Program in Movement Sciences São Paulo State University (UNESP) School of Physical Education and Sport of Ribeirao Preto University of Sao Paulo Laboratory of Nutritional Genomics (LabGeN) School of Applied Sciences University of Campinas (UNICAMP) Laboratory of Cell Signaling Obesity and Comorbidities Research Center (OCRC) University of Campinas CEPECE - Center of Research in Sport Sciences School of Applied Sciences University of Campinas (UNICAMP) Post-graduate Program in Movement Sciences São Paulo State University (UNESP) FAPESP: 2016/18488-8 CNPq: 306535/2017-3

Made available in DSpace on 2022-04-28T19:47:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Hepatic steatosis is directly associated with hepatic inflammation and insulin resistance, which is correlated with hyperglycemia and type 2 diabetes mellitus (T2DM). Aerobic and strength training have been pointed out as efficient strategies against hepatic steatosis. However, little is known about the effects of the combination of those two protocols on hepatic steatosis. Therefore, this study aimed to evaluate the impact of short-term combined training (STCT) on glucose homeostasis and in the synthesis and oxidation of fat in the liver of obesity-induced mice with hepatic steatosis. Swiss mice were distributed into three groups: control lean (CTL), sedentary obese (OB), and combined training obese (CTO). The CTO group performed the STCT protocol, which consisted of strength and aerobic exercises in the same session. The protocol lasted seven days. The CTO group reduced the glucose levels and fatty liver when compared to the OB group. Interestingly, these results were observed even without reductions in body adiposity. CTO group also showed increased hepatic insulin sensitivity, with lower hepatic glucose production (HGP). STCT reduced the expression of the lipogenic genes Fasn and Scd1 and hepatic inflammation, as well as increased the ACC phosphorylation and the oxidative genes Cpt1a and Ppara, reverting the complications caused by obesity. Since this protocol increased lipid oxidation and reduced hepatic lipogenesis, regardless of body fat mass decrease, it can be considered an effective non-pharmacological strategy for the treatment of hepatic steatosis. Exercise Cell Biology Lab Faculty of Applied Sciences University of Campinas Laboratory of Nutritional Genomics Faculty of Applied Sciences University of Campinas Motricity Sciences Institute of Biosciences São Paulo State University Julio de Mesquita Filho Multidisciplinary Laboratory of Food and Health Faculty of Applied Sciences University of Campinas School of Physical Education and Sport of Ribeirão Preto University of São Paulo (USP) Postgraduate Program in Rehabilitation and Functional Performance Ribeirão Preto Medical School USP Laboratory of Molecular Biology of Exercise Faculty of Applied Sciences University of Campinas Motricity Sciences Institute of Biosciences São Paulo State University Julio de Mesquita Filho FAPESP: 2015/07199-2 FAPESP: 2016/12569-6 FAPESP: 2016/24406-4

Loss of cardiomyocytes occurs with aging and contributes to cardiovascular complications. In the present study, we highlighted the role of clusterin, a protein that has recently been associated with the protection of cardiomyocytes from apoptosis. Clusterin protects cardiac cells against damage from myocardial infarction, transplant, or myocarditis. Clusterin can act directly or indirectly on apoptosis by regulating several intracellular pathways. These pathways include (1) the oxidant and inflammatory program, (2) insulin growth factor 1 (IGF-1) pathway, (3) KU70 / BCL-2-associated X protein (BAX) pathway, (4) tumor necrosis factor alpha (TNF-α) pathway, (5) BCL-2 antagonist of cell death (BAD) pathway, and (6) mitogen-activated protein kinase (MAPK) pathway. Given the key role of clusterin in preventing loss of cardiac tissue, modulating the expression and function of this protein carries the potential of improving cardiovascular care in the future.

Objective: Electronic cigarettes (e-cigs) are the most commonly used tobacco product by teens and young adults. The aim of the present study was to determine the potential effects of e-cig vapor exposure on cardiac function in adolescent mice. Materials and Methods: Adult FVB/NJ male and female mice were bred in our housing facility. Following birth, male offspring were raised in room air until weaning. At 3 weeks of age, mice were separated into two exposure groups: 1) E-cigarette exposure with nicotine (EC(+), N=5) (10.1 mg nicotine/1mL 50:50 propylene glycol:vegetable glycerin), or 2) E-cigarette exposure without nicotine (EC(-), N=4) and exposed for two months. A puff profile consisting of one 70-mL vapor puff per minute of exposure was administered for 4 h/day, 5 days/week over the course of two months. Cotinine concentration in the urine of mice from either group was determined using a cotinine ELISA kit. Echocardiography was used to examine global cardiac function after 1 and 2 months of exposure. Results: The average cotinine concentration in the urine of the EC(+) group after two months of exposure was 113.33 ng/mL, while there was not a detectable concentration of cotinine in the urine of EC(-) mice. Echocardiography showed no significant alterations in ejection fraction (%EF), fractional shortening (%FS), left ventricular end systolic diameter (LVES d ), or posterior wall thickness (PWT) between the EC(+) and EC(-) groups, nor any significant alterations between the first month and the second month timepoints for either group. Future Directions: Exposures will continue for longer durations until a cardiac phenotype becomes apparent. Once in vivo cardiac dysfunction becomes evident, we will investigate in vitro cardiomyocyte function.

Obesity and cardiovascular diseases are worldwide public health issues. In this review, we discussed the participation of ROCK protein in cardiac hypertrophy, mainly through the modulation of leptin and insulin signaling pathways. Leptin plays a role in cardiovascular disease development and, through the Rho-associated protein kinase (ROCK), promotes cardiac hypertrophy. ROCK protein, is regulated by small Rho-GTPases and has two isoforms with high homology. ROCK is able to activate the MAP kinase (MAPK) pathway and modulate insulin signaling in the heart, participating in cardiac hypertrophy development of concentric and eccentric left ventricle growth. Although different types of stimulus can lead to morphologically antagonistic heart growth, physical exercise promotes improvements in hemodynamic function, emerging as a promising non-pharmacological tool to improve overall health. Leptin can activate ROCK in a pathological way, increasing MAPK activity and decreasing insulin signaling via insulin receptor substrate 1 (IRS1) serine 307 residue phosphorylation, phosphatase and tensin homolog, and protein kinase Cβ2. In turn, physical exercise decreases leptin levels and positively modulates insulin signaling as well as increases ROCK-dependent IRS1 (Ser632/635) phosphorylation, improving phosphatidylinositol 3-kinase/protein kinase B axis and promoting physiologic heart growth. Currently, there is a lack of studies about differences in ROCK isoforms, especially during exercise and/or obesity. However, the understanding of its biological function and the complex mechanism underlying the distinct types of cardiac hypertrophy development can be a useful tool in the improvement and treatment of cardiovascular outcomes.

Made available in DSpace on 2021-06-25T12:26:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The impairment of the mitochondrial functions is a hallmark of aging. During aging, there is a downregulation of two mechanisms strictly associated with mitochondrial integrity, including the mitonuclear imbalance (eg, imbalance in mitochondrial- versus nuclear-encoded mitochondrial proteins) and the mitochondrial unfolded protein response (UPRmt). Here, we evaluated the effects of aerobic exercise in the mitonuclear imbalance and UPRmt markers in the skeletal muscle of old mice. We combined the physiological tests, molecular and bioinformatic analyzes to evaluate the effects of 4 weeks of aerobic exercise training on mitonuclear imbalance and UPRmt markers in the skeletal muscle of young (2 months) and aged (24 months) C57BL/6J mice. Initially, we found that aging reduced several mitochondrial genes in the gastrocnemius muscle, and it was accompanied by the low levels of UPRmt markers, including Yme1l1 and Clpp mRNA. As expected, physical training improved the whole-body metabolism and physical performance of aged mice. The aerobic exercise increased key proteins involved in the mitochondrial biogenesis/functions (VDAC and SIRT1) along with mitochondrial-encoded genes (mtNd1, mtCytB, and mtD-Loop) in the skeletal muscle of old mice. Interestingly, aerobic exercise induced the mitonuclear imbalance, increasing MTCO1/ATP5a ratio and UPRmt markers in the skeletal muscle, including HSP60, Lonp1, and Yme1L1 protein levels in the gastrocnemius muscle of aged mice. These data demonstrate that aerobic exercise training induced mitonuclear imbalance and UPRmt in the skeletal muscle during aging. These phenomena could be involved in the improvement of the mitochondrial metabolism and oxidative capacity in aged individuals. Univ Estadual Campinas, Lab Mol Biol Exercise, Limeira, Brazil Sao Paulo State Univ, Inst Biosci, Dept Phys Educ, Rio Claro, Brazil Univ Estadual Campinas, Lab Funct Properties Foods, Limeira, Brazil Univ Sao Paulo, Postgrad Program Rehabil & Funct Performance, Ribeirao Preto, Brazil Univ Sao Paulo, Sch Phys Educ & Sport Ribeirao Preto, Ribeirao Preto, Brazil Univ Estadual Campinas, Lab Nutr Genom, Limeira, Brazil Univ Estadual Campinas, CEPECE Ctr Res Sport Sci, Sch Appl Sci, UNICAMP, Limeira, Brazil Univ Estadual Campinas, Fac Med Sci, Dept Internal Med, UNICAMP, Campinas, SP, Brazil Sao Paulo State Univ, Inst Biosci, Dept Phys Educ, Rio Claro, Brazil CNPq: 304771/2017-1 CNPq: 401189/2016-3 CAPES: 001 FAPESP: 2018/07634-9

A pratica de exercicio fisico pode causar lesoes e danificar estruturas celulares, com isso, inicia-se o processo de autofagia a fim de degradar os elementos danificados. Parkin e responsavel por remover as mitocondrias danificadas (mitofagia) e assim prevenir a atrofia do musculo esqueletico. Alguns estudos indicam que a autofagia/mitofagia tem um papel importante na adaptacao do musculo esqueletico ao exercicio de resistencia. Sendo assim, torna-se de extrema importância estudar a relacao entre o processo de degradacao mitocondrial e a regeneracao muscular em resposta ao exercicio fisico de curto prazo. Com isso, o objetivo do estudo foi investigar se a capacidade de regeneracao muscular e potencializada devido ao treinamento fisico, assim como verificar a participacao de Parkin neste processo. Nossos resultados indicam que apesar dos animais treinados apresentarem menor area de lesao apos 3 dias, nao ha diferenca aos 10 dias de lesao. Com 10 dias de lesao, os animais treinados apresentaram maior numero de fibras de menor calibre. Alem disso, os animais treinados com 3 dias de lesao tiveram um acumulo de Pax-7, podendo indicar um maior numero de celulas satelites quiescentes ao inves de celulas em proliferacao. Sendo assim, o treinamento fisico previo a lesao pode estar atrasando o processo regenerativo do musculo esqueletico. No entanto, e necessaria uma analise a longo prazo a fim de confirmar esses resultados.

The number of studies that have evaluated exercise training (ET) and nitric oxide synthase (NOS)3 gene polymorphisms is scarce. The present study was designed to evaluate the relationship between exercise training and NOS3 polymorphisms at −786T>C, 894G>T, and intron 4b/a on blood pressure (BP) using 24-h ambulatory BP monitoring (ABPM), nitrate/nitrite levels (NO x), and redox state. Eighty-six volunteers (51 ± 0.6 yr old) were genotyped into nonpolymorphic and polymorphic groups for each of the three positions of NOS3 polymorphisms. Auscultatory BP, ABPM, SOD activity, catalase activity, NO x levels, and malondialdehyde levels were measured. DNA was extracted from leukocytes, and PCR followed by sequencing was applied for genotype analysis. Aerobic ET consisted of 24 sessions for 3 days/wk for 40 min at moderate intensity. This study was performed in a double-blind and crossover format. ET was effective in lowering office BP (systolic BP: 3.2% and diastolic BP: 3%) as well as ABPM (systolic BP: 2% and diastolic BP: 1.3%). Increased SOD and catalase activity (42.6% and 15.1%, respectively) were also observed. The NOS3 polymorphism for intron 4 mitigated the beneficial effect of ET for systolic BP (nonpolymorphic group: −3.0% and polymorphic group: −0.6%) and diastolic BP (nonpolymorphic group: −3.2% and polymorphic group: −0.5%), but it was not associated with NO x level and redox state. Paradoxical responses were found for positions T786-C and G894T for the NOS3 gene. Consistently, the presence of the polymorphism for intron 4 blunted the beneficial effects of ET in middle-aged adults. Possibly, this effect might be as consequence of intron 4 acting as a short intronic repeat RNA controlling endothelial NOS activity epigenetically.