Aging reveals a sex-dependent susceptibility of sarcospan-deficient mice to cardiometabolic disease.

Numerous genes including sarcospan (SSPN) have been designated as obesity-susceptibility genes by human genome-wide association studies. Variants in the SSPN locus have been linked with sex-dependent obesity-associated traits; however, this association has not been investigated in vivo. To delineate the role SSPN plays in regulating metabolism with potential to impact cardiac function, we subjected young and aged global SSPN-deficient (SSPN-/-) male and female mice to obesogenic conditions (60% fat diet). We hypothesized that loss of SSPN combined with metabolic stress would increase susceptibility of mice to cardiometabolic disease. Baseline and end-point assessments of several anthropometric parameters were performed including weight, glucose tolerance, and fat distribution of mice fed control (CD) and high-fat (HFD) diet. Doppler echocardiography was used to monitor cardiac function. White adipose and cardiac tissues were assessed for inflammation by histological, gene expression, and cytokine analysis. Overall, SSPN deficiency protected both sexes and ages from diet-induced obesity, with a greater effect in females. SSPN-/- HFD mice gained less weight than wild-type (WT) cohorts, while SSPN-/- CD groups increased weight. Furthermore, aged SSPN-/- mice developed glucose intolerance regardless of diet. Echocardiography showed preserved systolic function for all groups; however, aged SSPN-/- males exhibited significant increases in left ventricular mass (CD) and signs of diastolic dysfunction (HFD). Cytokine analysis revealed significantly increased IL-1α and IL-17Α in white adipose tissue from young SSPN-/- male mice, which may be protective from diet-induced obesity. Overall, these studies suggest that several sex-dependent mechanisms influence the role SSPN plays in metabolic responses that become evident with age.NEW & NOTEWORTHY Young and aged sarcospan (SSPN)-deficient mice were examined to assess the role of SSPN in obesity and cardiometabolic disease. Both sexes displayed a "leaner" phenotype in response to high-fat diet (HFD). Notably, several sex differences were identified in aged SSPN-deficient mice: 1) females developed glucose intolerance (control and HFD) and 2) males exhibited increased left ventricular mass (control) and diastolic dysfunction (HFD). Therefore, we conclude that SSPN exerts a sex-dependent influence on obesity-associated diseases.

A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice.

Sepsis is a major cause of in-hospital deaths. Improvements in treatment result in a greater number of sepsis survivors. Approximately 75% of the survivors develop muscle weakness and atrophy, increasing the incidence of hospital readmissions and mortality. However, the available preclinical models of sepsis do not address skeletal muscle disuse, a key component for the development of sepsis-induced myopathy. Our objective in this protocol is to provide a step-by-step guideline for a mouse model that reproduces the clinical setting experienced by a bedridden septic patient. Male C57Bl/6 mice were used to develop this model. Mice underwent cecal ligation and puncture (CLP) to induce sepsis. Four days post-CLP, mice were subjected to hindlimb suspension (HLS) for seven days. Results were compared with sham-matched surgeries and/or animals with normal ambulation (NA). Muscles were dissected for in vitro muscle mechanics and morphological assessments. The model results in marked muscle atrophy and weakness, a similar phenotype observed in septic patients. The model represents a platform for testing potential therapeutic strategies for the mitigation of sepsis-induced myopathy.

Autoimmunity as a sequela to obesity and systemic inflammation.

The rising prevalence of obesity presents a world-wide challenge as it is associated with numerous comorbidities including cardiovascular disease, insulin resistance and hypertension. Obesity-associated illnesses are estimated to cause nearly 4 million deaths globally per year, therefore there is a critical need to better understand associated pathogenesis, identify new therapeutic targets, and develop new interventions. Emerging data identify a key role for chronic inflammation in mediating obesity related disease states and reveal higher incidence of autoimmune disease development. Of the multiple potential mechanisms linking obesity and autoimmunity, the strongest link has been shown for leptin, a hormone secreted at high levels from obese white adipose tissue. Numerous studies have demonstrated that leptin enhances activation of both arms of the immune system, while its absence protects against development of autoimmunity. Other potential newly discovered mechanisms that contribute to autoimmune pathogenesis are not directly connected but also associated with obesity including sustained platelet activation, gut dysbiosis, and aging. Here we review how obesity instigates autoimmunity, particularly in the context of immune cell activations and adipokine secretion.

Equilíbrio hídrico em mulheres durante uma sessão de treinamento funcional de alta intensidade / Fluid balance in women during a session of high intensity functional training

O objetivo desse estudo foi avaliar o equilíbrio hídrico em mulheres durante uma sessão de treinamento funcional de alta intensidade (ex.: Crossfit). Vinte e duas mulheres fisicamente ativas (28 ± 7 anos, estatura = 167 ± 0.6 cm, massa corporal = 64,4 ± 9,6 kg) participaram do estudo. Uma amostra de urina foi obtida para a medida da gravidade específica da urina (GEU) e a massa corporal foi registrada. As participantes receberam garrafas contendo água para consumo ad libitum. A sessão de Crossfit consistiu em 10 min de aquecimento, em seguida, as participantes correram 400 m, realizaram 30 saltos sobre uma caixa e 30 arremessos de medicinebol. As participantes completaram quatro séries em 38 ± 7 minutos. A temperatura e umidade da sala foram 26,3 ± 1,5 °C e 47 ± 11% respectivamente. Após a sessão, a massa corporal foi novamente registrada e as garrafas pesadas para determinar a ingestão de líquidos. A GEU antes da sessão foi 1,018 ± 0,008 g/ml. Não houve alteração significativa na massa corporal durante a sessão de Crossfit (64,4 ± 9,6 vs. 64,5 ± 9,7 kg). A taxa de sudorese foi 0,6 ± 0,2 l/h e a taxa de ingestão de água foi 0,8 ± 0,2 l/h. Houve uma correlação positiva significativa entre a alteração na massa corporal e o total de líquido ingerido (r = 0,7990; r2 = 0,6384; p < 0.001). Algumas participantes ganharam peso por beber em excesso durante a sessão. Concluiu-se que o consumo ad libitum durante uma sessão de Crossfit pode ser suficiente para manter o equilíbrio hídrico em mulheres, porém, em alguns casos ocorreu consumo excessivo de líquidos.(AU)

The aim of this study was to evaluate fluid balance in women during a high intensity functional training session (e.g. Crossfit). Twenty-two physically active women (28 ± 7 years, height = 167 ± 0.6 cm, body mass = 64.4 ± 9.6 kg) participated in the study. A urine sample was obtained to determine the urine specific gravity (USG) and body mass was recorded. Participants were given bottles containing water to consume ad libitum. Crossfit session consisted of 10 min warm-up before participants ran 400 m, performed 30 jumps in a box and 30 throws of a medicine ball. The participants completed four sets in 38 ± 7 minutes. Room ambient temperature and humidity were 26.3 ± 1.5 ° C and 47 ± 11 %, respectively. After the session, body mass was recorded again and bottles were weighed to determine fluid intake. The USG before session was 1.018 ± 0.008 g/ml. There was no significant change in body mass during Crossfit session (64.4 ± 9.6 vs. 64.5 ± 9.7 kg). The sweat rate was 0.6 ± 0.2 l/h and the water intake was 0.8 ± 0.2 l/h. There was a significant positive correlation between body weight and total fluid intake (r = 0.7990; R2 = 0.6384, p < 0.001). Four participants gained weight by overdrinking during the session. In conclusion, ad libitum water may be enough to maintain fluid balance during a Crossfit session. However, some participants gained weight due to excessive fluid intake.(AU)

Improved exercise capacity in the heat followed by coconut water consumption

The aim of the present study was to assess the effects of prior ingestion of coconut water on fluid retention and exercise capacity in the heat as well as signs of gastrointestinal distress. Eight physically active men were recruited (age 23 ± 3 years, height 176 ± 6 cm, body mass 78 ± 7 kg) and performed three exercise capacity trials on a cycle ergometer in the heat (34 ± 1°C) after the ingestion of one of the following drinks: a) plain water (PW), b) flavored drink (FD), and c) coconut water (CW). Ingestion of CW resulted in a longer time to exhaustion (p=0.029). Likewise, participants achieved a higher heart rate in the CW session when compared to the other trials (PW 183 ± 5 bpm, FD 184 ± 8 bpm, and CW 189 ± 8 bpm, p<0.05) and a reduced urine output after the coconut water ingestion (PW 214 ± 85 ml, FD 267 ± 90 ml, and CW 161 ± 73 ml, p<0.05) indicating a higher fluid retention of coconut water in comparison to plain water and the flavored drink. These results demonstrate that previous ingestion of coconut water improves exercise capacity in the heat and provide a reduced urine output in comparison to plain water and flavored drink. Also there is no evidence for GI distress.

O objetivo do presente estudo foi avaliar os efeitos da ingestão prévia de água de coco sobre a retenção de líquidos e capacidade de resistência ao exercício no calor, bem como sinais de desconforto gastrointestinal. Oito homens fisicamente ativos foram recrutados (idade 23 ± 3 anos, altura 176 ± 6 cm, massa corporal 78 ± 7 kg) e realizaram três sessões de capacidade de exercício em uma bicicleta ergométrica no calor (34 ± 1° C) após a ingestão de uma das seguintes bebidas: a) água pura (PW), b) bebida com sabor (FD), e c) água de coco (CW). A ingestão de CW resultou num maior tempo até a exaustão (p = 0,029). Da mesma forma, os participantes alcançaram uma frequência cardíaca mais alta na sessão de CW quando comparado com as outras sessões (PW 183 ± 5 bpm, FD 184 ± 8 bpm, e CW 189 ± 8 bpm, p <0,05) e uma taxa de produção de urina reduzida após a ingestão de água de coco (PW 214 ± 85 ml, FD 267 ± 90 ml, e CW 161 ± 73 ml, p <0,05), indicando uma maior retenção de líquidos na sessão água de coco em comparação com água pura e bebida com sabor. Estes resultados demonstram que a ingestão prévia de água de coco melhora a capacidade de exercício no calor e proporciona uma menor produção de urina em comparação com a água pura e bebida com sabor. Também não houve nenhuma evidência de desconforto gastrointestinal.

El objetivo del presente estudio fue evaluar los efectos de la ingesta previa de agua de coco en la retención de líquidos y la capacidad de ejercicio al calor, así como señales de malestar gastrointestinal. Ocho hombres físicamente activos fueron reclutados (edad 23 ± 3 años, altura 176 ± 6 cm, la masa corporal de 78 ± 7 kg) y se realizaron tres ensayos de capacidad de ejercicio en un cicloergómetro con el calor (34 ± 1° C) después de la ingestión de una de las siguientes bebidas: a) agua potable (PW), b) bebida con sabor (FD), y c) el agua de coco (CW). La ingestión de CW dio lugar a un tiempo más largo hasta el agotamiento (p = 0,029). Del mismo modo, los participantes lograron una frecuencia cardíaca mayor en el CW en comparación con los otros ensayos (PW 183 ± 5 lpm, FD 184 ± 8 latidos por minuto, y CW 189 ± 8 latidos por minuto, p < 0,05 ) y una disminución del gasto urinario después del coco la ingestión de agua (PW 214 ± 85 ml, FD 267 ± 90 ml, y CW 161 ± 73 ml, p < 0,05) que indica una retención de líquidos mayor de agua de coco en comparación con agua pura y la bebida con sabor. Estos resultados demuestran que la ingesta previa de agua de coco mejora la capacidad de ejercicio en el calor y proporciona una disminución del gasto urinario en comparación con agua corriente y la bebida con sabor. Además, no hay evidencia de malestar gastrointestinal.