An assessment of thermoneutral housing conditions on murine cardiometabolic function

Mouse models are used to model human diseases and perform pharmacological efficacy testing to advance therapies to humans; most of these studies are conducted in room temperature conditions. At room temperature (22°C), mice are cold stressed and must utilize brown adipose tissue (BAT) to maintain body temperature. This cold stress increases catecholamine tone to maintain adipocyte lipid release via lipolysis, which will fuel adaptive thermogenesis. Maintaining rodents at thermoneutral temperatures (28°C) ameliorates the need for adaptive thermogenesis, thus reducing catecholamine tone and BAT activity. Cardiovascular tone is also determined by catecholamine levels in rodents, as beta adrenergic stimuli are primary drivers of not only lipolytic, but also ionotropic and chronotropic responses. As mice have increased catecholamine tone at room temperature, we investigated how thermoneutral housing conditions would impact cardiometabolic function. Here, we show a rapid and reversible effect of thermoneutrality on both heart rate and blood pressure in chow fed animals, which was blunted in animals fed high fat diet. Animals subjected to transverse aortic constriction displayed compensated hypertrophy at room temperature, while animals displayed less hypertrophy and trends towards worse systolic function at thermoneutrality. Despite these dramatic changes in blood pressure and heart rate at thermoneutral housing conditions, enalapril effectively improved cardiac hypertrophy and gene expression alterations. There were surprisingly few differences in cardiac parameters in high fat fed animals at thermoneutrality. Overall, these data suggest that thermoneutral housing may alter some aspects of cardiac remodeling in preclinical mouse models of heart failure.

Recent consumption of a caffeine-containing beverage and serum biomarkers of cardiometabolic function in the UK Biobank

We investigated the impact of recent caffeine drinking on glucose and other biomarkers of cardiometabolic function under free-living conditions while also accounting for lifestyle and genetic factors that alter caffeine metabolism and drinking behaviour. Up to 447 794 UK Biobank participants aged 37–73 years in 2006–2010 provided a non-fasting blood sample, for genetic and biomarker measures, and completed questionnaires regarding sociodemographics, medical history and lifestyle. Caffeine drinking (yes/no) about 1 h before blood collection was also recorded. Multivariable regressions were used to examine the association between recent caffeine drinking and serum levels of glycated Hb, glucose, lipids, apo, lipoprotein(a) and C-reactive protein. Men and women reporting recent caffeine drinking had clinically and significantly higher glucose levels than those not recently drinking caffeine (P < 0·0001). Larger effect sizes were observed among those 55+ years of age and with higher adiposity and longer fasting times (P ≤ 0·02 for interactions). Significant CYP1A2 rs2472297×caffeine and MLXIPL rs7800944 × caffeine interactions on glucose levels were observed among women (P = 0·004), with similar but non-significant interactions in men. Larger effect sizes were observed among women with rs2472297 CC or rs7800944 CC genotypes than among rs2472297 T or rs7800944 T carriers, respectively. In summary, men and women drinking caffeine within about 1 h of blood draw had higher glucose levels than those not drinking caffeine. Findings were modified by age, adiposity, fasting time and genetic factors related to caffeine metabolism and drinking behaviour. Implications for clinical and population studies of caffeine-containing beverages and cardiometabolic health are discussed.

Sex-Specific Associations Between Area-Level Poverty and Cardiometabolic Dysfunction Among US Adolescents

Objective: Cardiometabolic disease is the leading cause of mortality in the United States. Cardiometabolic function during adolescence predicts future cardiometabolic disease, yet few studies have examined early determinants of cardiometabolic function. Informed by evidence of sex differences in the prevalence and severity of cardiometabolic disorders and evidence of sexual dimorphism in the stress response, we examined sex differences in the association between living in poverty and cardiometabolic function during adolescence, a precursor of later cardiometabolic disorders. Methods: We linked data from 10 415 adolescents aged 12-19 in the National Health and Nutrition Examination Survey (1999-2012) with US Census–tract data on area-level poverty (percentage of the population living in poverty, grouped into quartiles). We parameterized cardiometabolic dysfunction by summing the z scores of 6 cardiometabolic biomarkers, grouped into quintiles. Hierarchical ordinal models estimated associations. Results: Compared with residents in low-poverty areas, residents in high-poverty areas had elevated odds of cardiometabolic dysfunction (highest quartile of poverty odds ratio [OR] = 1.27; 95% confidence interval [CI], 1.08-1.50). This association was more pronounced among boys than girls (highest quartile of poverty for boys: OR = 1.36; 95% CI, 1.10-1.70; highest quartile of poverty for girls: OR = 1.17; 95% CI, 0.94-1.47). Conclusion: Our study supports the existence of sex-specific associations. These results highlight the potential for community-based programs, such as housing assistance, to improve population health.