Inactivity, Obesity and Metabolic Syndrome

Obesity, Type II diabetes and metabolic syndrome

Obesity and Type 2 diabetes are epidemic health care problems that have both lifestyle (diet, inactivity) and genetic (familial risk) components. Metabolic syndrome is the presence of multiple risk factors for cardiometabolic disease that often leads to Type 2 diabetes and cardiovascular disease. These conditions have generated a tremendous amount of research and clinical interest, but because they are complex diseases with multiple roots, traditional research methods have not been adequate. We believe a systems biology approach to obesity research is the key to solving these problems.

Washington DC has one of the highest rates of childhood obesity (35%) in the U.S., a key future risk factor for Type 2 diabetes and adult obesity. It is estimated that greater than 85% of obese adolescents will become obese adults, contributing to escalating adult disease rates.  Given these epidemic levels, it is critical to understand risk factors for the early development of these chronic diseases and to identify mechanisms by which we can ameliorate and/or prevent them.

A Department of Genomics and Precision Medicine research team is working to identify genetic and molecular causes of childhood and adolescent obesity, understand the impacts of weight gain and weight loss on the body, and design interventions to reverse the fatal trajectory of weight gain in the nation’s children. This multidisciplinary team consists of basic and translational researchers, as well as clinician-scientists. An overarching hypothesis in our research states that genetic variations driving obesity will be more easily identified in younger populations that have fewer confounding disease co-morbidities than older, sicker populations. Furthermore, the early identification of individuals at higher risk for obesity and diabetes due to their genetics and lifestyles can lead to better prevention and treatment strategies.

A series of population-based interventions for inactivity, obesity, and Type 2 diabetes in children and young adults is underway within the Department. Recently, a Systems Biology of Obesity initiative was funded by the newly created Sheikh Zayed Institute for Pediatric Surgical Innovation. Monica Hubal, PhD, a new faculty member with dual backgrounds in exercise physiology and genetic medicine, is working with a newly recruited NIH-funded surgeon, Evan Nadler, MD, who performs bariatric surgery on extremely obese adolescents. Surgery projects include identification of genetic variations associated with successful health improvements after surgery and understanding the physiological changes that occur across organs (muscle, liver and fat) following surgery. Dr. Nadler also heads up the scientific team for the CNMC Obesity Institute, a multidisciplinary initiative with the goal of combating obesity through informed and comprehensive prevention and treatment programs.

The laboratory of Eric Hoffman, PhD, continued a series of NIH funded studies of genetic predispositions to metabolic syndrome and endophenotypes of type 2 diabetes in children and young adults. AIMM Young, led by Dr. Hoffman and Chiatogu Onyewu, MD, PhD, a study of metabolic syndrome in African American Washington, DC, college students has been highlighted by the NIH National Center on Minority Health and Health Disparities Health Disparities P20 Centers, with impressive recruitment. AIMM Young’s goal is to identify young people that are at risk for developing metabolic syndrome, with the intention of developing intervention programs that will arm students with tools to make lifestyle changes that lessen their chances of developing metabolic syndrome or progressing to Type 2 diabetes. Dr. Onyewu received a prestigious UNF-Merck fellowship to pursue research with Dr. Hoffman, as well as an NIH supplement for AIMM Young.

Dr. Hoffman (with Joseph M. Devaney, PhD) also continues work on the FAMUSS study, a multi-institutional cooperative study of young adults (average age 24 yrs), that seeks to identify genetic variations responsible for effects of strength training on muscle, bone, and fat mass. The FAMUSS study uses MRI, muscle strength testing, and response of these variables to 12 weeks of progressive supervised resistance training. To date, the FAMUSS study has resulted in 16 peer reviewed publications, including recent findings of genetic associations between variations in BMP2, INSIG2 and PPARA with muscle and fat mass.