The effects of sex hormones on the heart are dependent on the presence and distribution of sex steroid hormone receptors (SSHR) in cardiac tissue. This study used subcellular fractionation, Western blot analysis and densitometry to characterize the subcellular distribution and abundance of estrogen receptor (ER) alpha, ERbeta and androgen receptor (AR) in atrial and ventricular tissue from male and female mice. The results showed that in both atrial and ventricular tissue ERalpha was primarily found in the sarcolemma, whereas ERbeta and AR were predominantly located in the nucleus and cytosol. Interestingly, ERalpha expression was greater in the ventricles compared to the atria, whereas ERbeta and AR expression were similar in both heart chambers. Furthermore, the distribution and abundance of SSHR in the atria and ventricles did not differ between sexes. This study also showed that a reduction in hormone levels (as a result of ovariectomy) resulted in a significant increase in the abundance of ERalpha in the ventricular sarcolemmal fraction. Overall, the results suggest ERalpha, ERbeta and AR distribution and expression are not sex dependent in the mouse heart. However, it appears that ERalpha expression is chamber specific and that, in certain cases, hormone levels can modulate the subcellular location of SSHRs.

The gut microbiome is known to have a complex yet vital relationship with host health. While both exercise and the gut microbiome have been shown to impact human health independently, the direct effects of moderate exercise on the intestinal microbiota remain unclear. In this study, we compared gut microbial diversity and changes in inflammatory markers associated with exercise over an 8-week period in mice that performed either voluntary exercise (VE) (n = 10) or moderate forced exercise (FE) (n = 11) and mice that did not perform any exercise (n = 21). VE mice, but not FE mice, had increased food intake and lean body mass compared to sedentary mice. The levels of inflammatory markers associated with exercise were similar for mice in all three groups. Traditional microbial profiles comparing operational taxonomic units (OTUs) in samples (P > 0.1) and multivariate analysis of beta diversity via Adonis testing (P > 0.1) did not identify significantly altered taxonomic profiles in the voluntary or forced exercise group compared to the sedentary controls. However, a random forests machine learning model, which takes into account the relationships between bacteria in a community, classified voluntary exercisers and nonexercisers with 97% accuracy at 8 weeks. The top bacteria used by the model allowed us to identify known taxa (Bacteroides, S24-7, and Lactobacillus) and novel taxa (Rikenellaceae and Lachnospiraceae) associated with exercise. Although aerobic exercise in mice did not result in significant changes of abundance in gut microbes or in host inflammatory response, more sophisticated computational methods could identify some microbial shifts. More study is needed on the effects of various exercise intensities and their impact on the gut microbiome. IMPORTANCE The bacteria that live in our gut have a complex yet vital relationship with our health. Environmental factors that influence the gut microbiome are of great interest, as recent research demonstrates that these microbes, mostly bacteria, are important for normal host physiology. Diseases such as obesity, diabetes, inflammatory bowel disease, and colon cancer have also been linked to shifts in the microbiome. Exercise is known to have beneficial effects on these diseases; however, much less is known about its direct impact on the gut microbiome. Our results illustrate that exercise has a moderate but measurable effect on gut microbial communities in mice. These methods can be used to provide important insight into other factors affecting the microbiome and our health.

A frailty index based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 & 23-months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool. Interestingly, while FI-Clinical scores were higher in females, the opposite was true for FI-Lab scores and there was no sex difference in FI-Combined scores. All three FI tools revealed a positive correlation between pro-inflammatory cytokine levels and frailty in aging mice that differed between the sexes. Elevated levels of the pro-inflammatory cytokines interleukin-6, interleukin-9 and interferon-γ were associated with higher FI scores in aging females, while levels of interleukin-12p40 rose as FI scores increased in older males. Thus, an FI tool based on common laboratory tests can quantify frailty in mice; the positive correlation between inflammation and frailty scores in naturally-aging mice differs between the sexes.

This study characterized age-related alterations in excitation-contraction (EC)-coupling in ventricular myocytes and investigated whether these alterations are affected by the sex of the animal. Voltage-clamp experiments were conducted in myocytes from young adult (∼7 mo) and aged (∼24 mo) male and female mice. Intracellular Ca²⁺ concentrations and unloaded cell shortening were measured at 37°C with fura-2 and a video edge detector. Fractional shortening and Ca²⁺ current density were significantly reduced in aged male myocytes compared with those in young adult male cells. In addition, Ca²⁺ transients were significantly smaller in aged male myocytes. Sarcoplasmic reticulum (SR) content, assessed by rapid application of 10 mM caffeine, declined with age in male myocytes. However, EC coupling gain and fractional release of SR Ca²⁺ were similar in young adult and aged male cells. In contrast to results in male animals, fractional shortening and Ca²⁺ current densities were similar in young adult and aged myocytes isolated from female hearts. Furthermore, Ca²⁺ transient amplitudes were unaffected by age in female cells. Interestingly, SR Ca²⁺ content was elevated in aged female myocytes, and fractional SR Ca²⁺ release declined with age in females. However, the gain of EC coupling was not different in myocytes from young adult and aged female mice. These data demonstrate that age-related alterations in EC coupling are more prominent in myocytes from male hearts than in cells from female hearts and suggest that it is important to consider sex as a variable in studies of the effects of aging on cardiac EC coupling.

Objectives: The prevalence of obesity among populations in the Atlantic provinces is the highest in Canada. Some studies suggest that adequate fruit and vegetable consumption may help body weight management. We assessed the associations between fruit and vegetable intake with body adiposity among individuals who participated in the baseline survey of the Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) cohort study.Methods: We carried out a cross-sectional analysis among 26 340 individuals (7979 men and 18 361 women) aged 35–69 years who were recruited in the baseline survey of the Atlantic PATH study. Data on fruit and vegetable intake, sociodemographic and behavioural factors, chronic disease, anthropometric measurements and body composition were included in the analysis.Results: In the multivariable regression analyses, 1 SD increment of total fruit and vegetable intake was inversely associated with body mass index (−0.12 kg/m²; 95% CI −0.19 to –0.05), waist circumference (−0.40 cm; 95% CI −0.58 to –0.23), percentage fat mass (−0.30%; 95% CI −0.44 to –0.17) and fat mass index (−0.14 kg/m²; 95% CI −0.19 to –0.08). Fruit intake, but not vegetable intake, was consistently inversely associated with anthropometric indices, fat mass, obesity and abdominal obesity.Conclusions: Fruit and vegetable consumption was inversely associated with body adiposity among the participant population in Atlantic Canada. This association was primarily attributable to fruit intake. Longitudinal studies and randomised trials are warranted to confirm these observations and investigate the underlying mechanisms.

The Atlantic Partnership for Tomorrow’s Health (Atlantic PATH) study is a regional cohort of the Canadian Partnership for Tomorrow Project (CPTP) which is a multi-centred prospective cohort study. ¹ Prospective cohort studies that follow participants over time provide an opportunity to better understand how genetics, environment and lifestyle factors interact to affect the development of chronic health outcomes. The CPTP involves five regional cohorts in eight provinces, including Atlantic PATH, Alberta’s Tomorrow Project, the Ontario Health Study, the British Columbia Generations Project and CARTaGENE (Quebec). The CPTP was established in 2008 with a goal of recruiting 300 000 participants from across Canada in order to examine the complex interplay of factors that lead to the development of cancer and other chronic diseases. ² CPTP participants will be followed actively and passively over a period of 30 years – actively with requests for additional questionnaire data, biological samples or physical measurements, and passively by linking to provincial health records in order to determine future health outcomes.