Biomarkers and Genetics Laboratory (BAGL)

The primary focus of the BAGL is to gain a better understanding of the genesis of the metabolic syndrome during childhood and adolescence. The long-term goal of this research is to elucidate the mechanisms of the metabolic syndrome through the complex interactions of genetics, environmental factors (particularly stress, exercise, diet, and maternal factors), and the neuroendocrine, hormonal, metabolic, hemostatic and inflammatory systems in the growing and maturing obese child. An understanding of these complex interactions in the obese adolescent may provide a better understanding of the etiology of the metabolic syndrome, Type II diabetes and atherosclerosis and the prevention and treatment of these clinical disorders in the obese adolescent.

The obese child generally displays an adverse cardiovascular disease (CVD) risk factor profile that includes elevated blood pressure, glucose, and triglycerides and lowered high-density lipoprotein-cholesterol. This constellation of obesity and CVD risk factors has been termed the metabolic syndrome. In addition, new emerging risk factors related to hemostasis, fibrinolysis, and inflammation have been identified in the obese child and some of these biomarkers are actually secretory proteins of the adipocyte – known as adipocytokines or adipokines. Several factors may contribute to the emergence of the metabolic syndrome in adolescence including genetics, reduced daily energy expenditure, low aerobic fitness, and dysregulation of the hypothalamic-pituitary-adrenal or sympathomedullary axis during puberty.

It is important to understand these associations given the potential roles of genetics, habitual physical activity, aerobic fitness, and stress on the etiology of the metabolic syndrome, Type 2 diabetes, and CVD during childhood growth and puberty. The long-term goal of this research is to elucidate the mechanisms of the metabolic syndrome through the complex interactions of genetics, environmental factors (particularly stress, exercise, and diet), and the neuro-endocrine, hormonal, metabolic, hemostatic and inflammatory systems in the growing and maturing obese child. An understanding of these complex interactions in the obese adolescent may provide a better understanding of the etiology of the metabolic syndrome, Type II diabetes and atherosclerosis and the prevention and treatment of these clinical disorders in the obese adolescent.

Current Projects

• Genetics, physical activity, and obesity-hypertension in young children. The objective of this study is to examine the longitudinal development of the adiposity and BP phenotypes in young children taking into account physical activity and the angiotensinogen converting enzyme (ACE) polymorphism. We chose to study ACE polymorphisms since it is a positional candidate gene that may have pleiotropic effects on adiposity and BP. In the context of human growth, it has been suggested that a master gene has pleiotropic control over somatic growth, obesity and BP. Given the potential roles of adiposity, physical activity and genes and their interactions on the etiology of the hypertension during early life, it is critical that we increase our understanding of the genesis of obesity and hypertension and develop appropriate prevention and treatment strategies. This project is currently funded by the American Heart Association. Collaborators include: Dr. Kate Heelan, University of Nebraska-Kearney; Dr. Greg Welk, Iowa State University; Dr. Max Rothschild, Iowa State University; Dr. Adam Baxter-Jones, University of Saskatchewan.
• Genetics, adolescent fatness and fitness as predictors of adult metabolic syndrome. In this study, we are addressing if adolescent growth is related to subsequent adult disease by following subjects from the Saskatchewan Growth and Development Study (SGDS, 1964-1973) who are now approaching the age of 50 years of life, which is about the time that the clinical manifestations of CVD and type 2 diabetes occurs. Given the longitudinal design of the SGDS we can also investigate the influence of longitudinal growth trajectories during adolescence on adult health outcomes; unlike cross-sectional associations between one-time adolescent and adult measures used in previous studies, the proposed study design allows us to calculate growth trajectories which incorporate change over the entire period. This work will identify potential antecedents in early life that affect the metabolic syndrome. Funding for this project is from the Canadian Institutes of Health Research (Co-investigator with Dr. Adam Baxter-Jones, University of Saskatchewan).
• Physical activity, stress, and new emerging risk factors. The objective of this project is examine the inter-relationships among energy expenditure, aerobic fitness, stress, and emerging risk factors in highly active runners, obese, and non-obese adolescent boys. Forty 12-20 yr old males were assessed for physical activity, aerobic fitness, stress, fatness, and emerging risk factors. Outcomes of this research will be important in understanding the complex physiological interactions that lead to the metabolic syndrome, and the prevention and treatment of the obese adolescent.

• Physical activity, stress, and the metabolic syndrome. The objective of this study is to gain an understanding of the role of stressors on the genesis of the metabolic syndrome during puberty. This project has two specific aims:

  • Examine the stress response to psychological and physical perturbations in obese and non-obese adolescents. In this study, measurement of salivary cortisol will be used as an indicator of HPA axis activity and BP and heart rate will be used as indicators of the SAM axis. We hypothesize an exaggerated stress response in obese adolescents compared to non-obese adolescents.
  • Examine the relationships among energy expenditure, cortisol, and atherosclerotic risk factors in obese and non-obese adolescents. We hypothesize a direct relationship between baseline cortisol levels and atherosclerotic risk factors and more specifically we hypothesize that physical activity will modify the relationship between cortisol and atherosclerotic risk factors.

  This research was supported by the Center for Designing Food and Improving Nutrition, Iowa State University through the U.S. Department of Agriculture.

• Effects of physical activity on the metabolic syndrome during postnatal development in mice selectively bred for high capacity running: an ontogenetic model of the metabolic syndrome. An alternative to longitudinal studies of human children and adolescents is the postnatal animal model. We are beginning collaborations with Dr. Ted Garland (University of California-Riverside) to use a novel animal model to examine the unique and combined contributions of genetics and physical activity on the postnatal development of the metabolic syndrome. Here, we will use mice that have been selectively bred to run voluntarily on wheels almost 200% more than non-selected lines (controls). The objective of this study is to gain an understanding of the role of genetics and physical activity on the genesis of the metabolic syndrome during postnatal development using a novel animal model. This project has two specific aims:

  • Examine the ontogeny of the metabolic syndrome in two strains of mice – one selectively bred for high levels of voluntary exercise and a control line.
  • Examine the effects of physical activity (access to a running wheel) on the ontogeny of the metabolic syndrome in both strains of mice.

  This work is currently supported from a Michigan State University Seed Grant.

Related Publications

• M Holmes, JC Eisenmann, D Gentile,P Ekkekakis. Physical activity, stress and metabolic risk score of adolescent males. J Phys Activity Health (in press).
• JC Eisenmann.  Aerobic fitness, fatness, and the metabolic syndrome in children and adolescents. Acta Pediatr (in press).
• JC Eisenmann and K Tolfrey. Genetics and pediatric exercise science: a commentary and review. Pediatric Exercise Science(in press).
• K DuBose, JC Eisenmann, JE Donelly. Aerobic fitness attenuates the metabolic syndrome score in normal weight, at-risk-for-overweight, and overweight children Pediatrics (in press).
• JC Eisenmann, GJ Welk, MA Ihmels, J Dollman. Fitness, fatness and cardiovascular disease risk factors in children and adolescents. Medicine Science Sports Exercise 39:1251-1256, 2007.
• JC Eisenmann, K DuBose, JE Donnelly. Fatness, fitness, and insulin resistance among 7-9 yr old children. Obesity 15 2135-2144, 2007.
• JC Eisenmann, GW Welk, EE Wickel, and SN Blair. Combined influence of cardiorespiratory fitness and body mass index on cardiovascular disease risk factors among 8-18 year old youth: The Aerobics Center Longitudinal Study International Journal of Pediatric Obesity 2: 66-72, 2007.
• JC Eisenmann, P Ekkekakis, M Holmes. Sleep duration and overweight in children and adolescents.  Acta Pediatrica 95:956-963, 2006.
• JC Eisenmann.  Insight into the causes of the recent secular trend in pediatric obesity:  common sense does not always prevail for complex, multi-factorial phenotypes.  Preventive Medicine 42:329-335, 2006.
• JC Eisenmann J Wrede, K Heelan. Associations between adiposity, family history of CHD and blood pressure in 3-8 yr old children.  Journal of Human Hypertension 19:675-681, 2005.
• J C Eisenmann, P T Katzmarzyk, L Perusse, A Tremblay, J-P Després and C Bouchard. Aerobic fitness, body mass index, and CVD risk factors among adolescents: the Quebec Family Study.  Int J Obes Relat Metab Disord
• JC Eisenmann, EE Wickel, GJ Welk, SN Blair. Relationship between adolescent fitness and fatness and cardiovascular disease risk factors in adulthood: the Aerobics Center Longitudinal Study.American Heart Journal 149:46-53, 2005.
• JC Eisenmann, EE Wickel, GJ Welk, SN Blair. Stability of cardiovascular disease risk factors in from adolescence into adulthood: the Aerobics Center Longitudinal Study. American Journal of Human Biology 16:690-696, 2004.
• K. Garcia, J.C. Eisenmann, R.T. Bartee. Does a family history of CHD modify the relationship between physical activity and blood pressure in young adults? European Journal of Cardiovascular Rehabilitation and Prevention
• J.C. Eisenmann. Physical activity and cardiovascular disease risk factors in children and adolescents: an overview. Canadian Journal of Cardiology
• J.C. Eisenmann. Secular trends in variables associated with the metabolic syndrome among North American children and adolescents. American Journal of Human Biology, 15:786-794, 2003.
• J.C. Eisenmann and R.M. Malina. Changes in subcutaneous adipose tissue in young distance runners and association with blood lipoproteins.  Annals of Human Biology, 29:389-397, 2002.
• J.C. Eisenmann.  Blood lipids and lipoproteins in the child and adolescent athlete. Sports Medicine, 32(5):297-307, 2002.