Skeletal muscle and nuclear hormone receptors: Implications for cardiovascular and metabolic disease

Skeletal muscle is a major mass peripheral tissue that accounts for similar to 40% of the total body mass and a major player in energy balance. It accounts for > 30% of energy expenditure, is the primary tissue of insulin stimulated glucose uptake, disposal, and storage. Furthermore, it influences metabolism via modulation of circulating and stored lipid (and cholesterol) flux. Lipid catabolism supplies up to 70% of the energy requirements for resting muscle. However, initial aerobic exercise utilizes stored muscle glycogen but as exercise continues, glucose and stored muscle triglycerides become important energy substrates. Endurance exercise increasingly depends on fatty acid oxidation (and lipid mobilization from other tissues). This underscores the importance of lipid and glucose utilization as an energy source in muscle. Consequently skeletal muscle has a significant role in insulin sensitivity, the blood lipid profile, and obesity. Moreover, caloric excess, obesity and physical inactivity lead to skeletal muscle insulin resistance, a risk factor for the development of type II diabetes. In this context skeletal muscle is an important therapeutic target in the battle against cardiovascular disease, the worlds most serious public health threat. Major risk factors for cardiovascular disease include dyslipidemia, hypertension, obesity, sedentary lifestyle, and diabetes. These risk factors are directly influenced by diet, metabolism and physical activity. Metabolism is largely regulated by nuclear hormone receptors which function as hormone regulated transcription factors that bind DNA and mediate the pathophysiological regulation of gene expression. Metabolism and activity, which directly influence cardiovascular disease risk factors, are primarily driven by skeletal muscle. Recently, many nuclear receptors expressed in skeletal muscle have been shown to improve glucose tolerance, insulin resistance, and dyslipidernia. Skeletal muscle and nuclear receptors are rapidly emerging as critical targets in the battle against cardiovascular disease risk factors. Understanding the function of nuclear receptors in skeletal muscle has enormous pharmacological utility for the treatment of cardiovascular disease. This review focuses on the molecular regulation of metabolism by nuclear receptors in skeletal muscle in the context of dyslipidemia and cardiovascular disease. (c) 2005 Published by Elsevier Ltd.

Genetic Influences on Exercise Participation in 37.051 Twin Pairs from Seven Countries

Background A sedentary lifestyle remains a major threat to health in contemporary societies. To get more insight in the relative contribution of genetic and environmental influences on individual differences in exercise participation, twin samples from seven countries participating in the GenomEUtwin project were used. Methodology Self-reported data on leisure time exercise behavior from Australia, Denmark, Finland, Norway, the Netherlands, Sweden and United Kingdom were used to create a comparable index of exercise participation in each country (60 minutes weekly at a minimum intensity of four metabolic equivalents). Principal Findings Modest geographical variation in exercise participation was revealed in 85,198 subjects, aged 19–40 years. Modeling of monozygotic and dizygotic twin resemblance showed that genetic effects play an important role in explaining individual differences in exercise participation in each country. Shared environmental effects played no role except for Norwegian males. Heritability of exercise participation in males and females was similar and ranged from 48% to 71% (excluding Norwegian males). Conclusions Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality. This collaborative study suggests that attempts to find genes influencing exercise participation can pool exercise data across multiple countries and different instruments

The association between number of homework assignments completed during a lifestyle physical activity intervention and scores on transtheoretical measures

An assumption of theory-based physical activity interventions is that active participation positively affects the theoretical constructs upon which the intervention is based. This assumption is rarely tested. This study assessed whether participation, defined as completion of homework, in a lifestyle physical activity intervention was associated with changes over 6 months in constructs the homework addressed: the behavioral and cognitive processes of change, self-efficacy, and decisional balance (the pros and cons). Participants were 244 sedentary adults aged 25 to 75 years. They completed an average of 12 of 20 homework assignments. Those completing at least two-thirds of the homework (n = 113) had greater changes in the theoretical constructs from pretest to posttest than those completing less (n = 90). Post-hoc analyses suggest that completing theory-based homework may impact the processes of change and self-efficacy in lifestyle physical activity interventions and, therefore, are warranted in future interventions.

Residential and lifestyle changes for adults with an intellectual disability in Queensland 1960-2001

As we celebrate 50 years of the Schonell Special Education Research Centre it is timely to consider changes that have occurred in the provision of residential services for people with an intellectual disability. Before the 1970s adults and children were cared for in large institutions using a medical model of care. In the mid-1970s a new developmental model based on education and training was implemented in response to the principle of normalisation and issues of social justice. The most dramatic changes have occurred in the last ten years with the decision to close large institutions and relocate residents into ordinary homes in the community. This paper describes changes in lifestyle for adults with an intellectual disability as a result of the move from institutional to community residential service provision. The Challinor Centre in Ipswich, Queensland, Australia provides examples of lifestyle changes that have occurred under different models of service provision during this time. Community living is described with research evidence validating the advantages of this type of service provision for residents with an intellectual disability. Outcomes have been documented through the use of group results and a case study of one individual following deinstitutionalisation describes the benefits of this new model of residential accommodation

Lifestyle still predicts mortality in older men with established vascular disease

Background. It is uncertain whether accepted associations between health behaviors and mortality are pertinent to elderly people. No previous studies have examined the patterns of lifestyle in elderly men with and without clinically evident vascular disease by using a lifestyle score to predict survival. Methods. We measured prevalence of a healthy lifestyle (four or more healthy behaviors out of eight) and examined survival in 11,745 men aged 65-83 years participating in a randomized population-based trial of screening for abdominal aortic aneurysm in Perth, Western Australia. After stratifying participants into five groups according to history and symptoms of vascular disease, we compared survival of men in each subgroup with that of 'healthy' men with no history or symptoms of vascular disease. Results. Invitations to screening produced a corrected response of 70.5%. After adjusting for age and place of birth, having an unhealthy lifestyle was associated with an increase of 20% in the likelihood of death from any cause within 5 years (95% CI: 10-30%). This pattern was consistently evident across subgroups defined by history of vascular disease, but was less evident for deaths from vascular disease. Conclusions. Our results highlight the importance of maintaining a healthy lifestyle through to old age, regardless of history of vascular disease. (c) 2005 Elsevier Inc. All rights reserved.

A simple lifestyle score predicts survival in healthy elderly men

Background. Although improvements in life expectancy have been attributed in part to the adoption or a more prudent lifestyle, few studies have examined the association of lifestyle with survival, using several lifestyle factors simultaneously, in a healthy elderly population. Methods. We investigated the association of health related behaviors with mortality in 7989 men aged 65 to 83 years participating in a population-based trial in Perth, Western Australia, by calculating a lifestyle score as a simple tally of flow many or eight prudent behaviors each individual followed. Results. Invitations to screening produced a corrected response of 70.5%. Out of a possible score of 8.46% of men had a score of less than 5. Within 5 years, a total of 703 men (9%) had died from any cause. The hazard ratio in men with a low lifestyle score was 1.3 [95% confidence interval (CI): 1.1-1.5] compared with men with a score of 5 or more. Conclusions. Lifestyle remains an important predictor of mortality even in old age. Survival in older men without a history of cardiovascular disease can potentially be enhanced by promoting a healthy lifestyle. © 2004 Elsevier Inc, All rights reserved.

Socioeconomic disadvantage and changes in health risk behaviours in Australia: 1989-90 to 2001

Objective. Lower socioeconomic status (SES) is associated in industrialized countries with unhealthy lifestyle characteristics, such as smoking, physical inactivity and being overweight or obese. This paper examines changes over time in the association between SES and smoking status, physical activity and being overweight or obese in Australia. Methods. Data were taken from three successive national health surveys in Australia carried out in 1989-90 (n = 54 576), 1995 (n = 53 828) and 2001 (n = 26 863). Participants in these surveys were selected using a national probability sampling strategy, and aggregated data for geographical areas are used to determine the changing association between SES and lifestyle over time. Findings. Overall, men had less healthy lifestyles, In 2001 inverse SES trends for both men and women showed that those living in lower SES areas were more likely to smoke and to be sedentary and obese, There were some important socioeconomic changes over the period 1989-90 to 2001. The least socioeconomically disadvantaged areas had the largest decrease in the percentage of people smoking tobacco (24% decrease for men and 12% for women) and the largest decrease in the percentage of people reporting sedentary activity levels (25% decrease for men and 22% for women). While there has been a general increase in the percentage over time of those who are overweight or obese, there is a modest trend for being overweight to have increased (by about 16% only among females) among those living in areas of higher SES. Conclusion. Socioeconomic inequalities have been increasing for several key risk behaviours related to health; this suggests that T specific population-based prevention strategies intended to reduce health inequalities are needed.