Obesity & Metabolic Disease

Obesity rates have been rising steadily in many parts of the world and, along with them, the incidence of diabetes and other metabolic diseases. The complications of these diseases impact nearly every medical specialty, every day. The University of Michigan Department of Surgery is visionary in its approach to changing this fact, dedicating a broad range of initiatives and resources to better understand, prevent and treat obesity and metabolic disease.

Currently, few good therapies exist to treat obesity. Bariatric surgery has proven the most effective to date, but it doesn't work for all patients. It's also invasive and, depending on the procedure, irreversible, and it's not scalable to treat the large number of patients who meet the criteria. Our work is leading us to think about interventions, like bariatric surgery, in new ways. Faculty findings show that success is related less to physical restriction of food intake and more upon changes in signaling among the brain, gut, pancreas and liver.

With the overarching goal to offer patients new and better options, our research spans basic, translational, clinical and health services delivery and outcomes investigations. The Department has earned a reputation for its use of advanced tools, such as RNA sequencing and novel animal models, to study the circuitry involved in hunger, food intake, satiety and metabolism.

Examples of faculty work include:

• Research into the hormones and signaling pathways that control appetite, energy balance and body weight. Findings are yielding insights into how gut-brain communications influence obesity-related diseases, such as non-alcoholic steatohepatitis, or NASH. 

• Investigations into the peptide GLP1, produced in the brain, intestine and pancreas, that have shown the critical role of pancreatic GLP-1 in regulating glucose homeostasis. This discovery is important to better targeting GLP1 agonists in the treatment of diabetes. 

• Elucidation of the role certain immune cells, adipocyte stem cells, and signaling pathways play in fat, or adipose, tissue dysfunction connected with obesity and type 2 diabetes.

• Identification of the epigenetic and signaling mechanisms that impact wound healing in patients with diabetes. 

• Studies to understand the role of changes in bile acids and their receptors —previously under-appreciated players — in metabolic improvements following bariatric surgery.
• Investigations into the role obesity and metabolic disease play in classical surgical topics, such as trauma recovery, sepsis and cancer development, progression and treatment. 

Health services research also is critical to our work, enabling us to improve — and develop new — procedures, minimize complications and enhance outcomes. Findings also help us predict the response to interventions so that we can identify therapies mostly likely to achieve the best results for each of our patients. Several of the Department's faculty lead and participate in the Michigan Bariatric Surgery Collaborative (MBSC), a national model for improving bariatric surgical care. 

The MBSC has improved the safety of bariatric surgery in Michigan in several ways:

• Lowering the risk of complications, such as wound infections and blood clots
• Lessening the use of unnecessary procedures
• Reducing hospital readmissions
• Creating tools to help guide patients to the best procedure for them.

Unparalleled Resources for Research and Research Education

Our faculty have developed several robust resources, including a tissue bank of human visceral and subcutaneous adipose tissue and sophisticated in vitro two-dimensional and three-dimensional human cell culture systems. We also train the next generation of surgeon-scientists with the support of a competitive National Institutes of Health T32 training grant in bariatric surgical science. Ours is the only such grant in the United States focused on bariatric surgery research training, structured to equally support both basic science and health services research.

Our obesity and metabolic disease research is highly collaborative and multidisciplinary, with many initiatives across campus, the State of Michigan and the nation. 

Michigan Nutrition Obesity Research Center (MNORC)

Since 2009, Department of Surgery faculty have led the Michigan Nutrition Obesity Research Center (MNORC). Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, MNORC directs several research cores that enable an innovative portfolio of obesity research at the University of Michigan. We are proud to be the only department of surgery in the country to run such a center.

Michigan Bariatric Surgery Collaborative (MBSC)

The Michigan Bariatric Surgery Collaborative (MBSC), housed in U-M's North Campus Research Complex, touches nearly every patient who undergoes bariatric surgery in the State of Michigan. With its extensive clinical registry, the MBSC analyzes data to identify best practices and techniques to improve the delivery and outcomes of these procedures. 

Faculty collaborate closely with other investigators throughout the University community, including to:

• Understand the role of subpopulations of neurons in the brain stem and signaling mechanisms that regulate glucose metabolism to identify new therapeutic targets (Dr. Randy Seeley with Dr. Martin Myers of Internal Medicine and Dr. David Olsen of Pediatric Endocrinology)

• Explore the role of the kidneys in glucose metabolism and the use of renal nerve stimulation to improve glucose control (Dr. Randy Seeley and Dr. Paul Cederna with Assistant Professor of Biomedical Engineering Tim Bruns)
• Study the role of adipose tissue in regulating metabolic disease in the context of diabetes, and develop methods for “engineering” metabolically healthy adipose tissue (Dr. Robert O’Rourke, in collaboration with Dr. Carey Lumeng, Department of Pediatrics, and Dr. Lonnie Shea, Department of Biomedical Engineering).
• Define the mechanisms by which adipose tissue communicates with cancer cells in patients with pancreatic cancer (Dr. Robert O’Rourke and Dr. Timothy Frankel, Department of Surgery)

Department faculty also maintain strong collaborations with partners in the medical device, food and pharmaceutical industries to develop new and next-generation therapeutic products.