Dr. Buettner is an endocrinologist with a longstanding interest in metabolic regulation and diabetes. His lab studies the regulation of metabolism through the central nervous system with a focus on liver and adipose tissue as targets of CNS control of metabolism. He has a longstanding interest in the actions of hypothalamic leptin and insulin signaling and the metabolic pathways that are regulated in peripheral tissues such as hepatic gluconeogenesis, adipose tissue lipolysis, and lipogenesis. Further, he has elucidated how hypothalamic insulin and leptin govern hepatic glucose production, VLDL secretion, amino acid metabolism and systemic inflammation. He has studied mechanisms through which obesity and diabetes, but also alcohol and Alzheimer’s impair hypothalamic insulin action resulting in dysregulated nutrient partitioning and a pro-inflammatory state. More recently, he is examining the role of adipose tissue function in regulating hypothalamic function. As a prime communicator between the CNS and the periphery, the autonomic nervous system plays pivotal roles in regulating hepatic glucose, lipids, and amino acid metabolism. We have developed novel approaches and employ innovative techniques such as organ-specific denervation, monitoring in vivo neurotransmitter release and cAMP signaling, and several transgenic mice models to elucidate the function of the sympathetic nervous system in regulating nutrient partitioning, energy homeostasis, and inflammation.
Research Topics:
Endocrinology, Diabetes & Metabolism, Brain control of Metabolism, Sympathetic Nervous System and Metabolic Syndrome, Microglia, Hypothalamic Inflammation, Glucose Counterregulation, Microbiome and Metabolic Control, Diabetes and Traumatic Brain Injury, Lipid Metabolism and Alzheimer's Disease
Research Interests:
In the Buettner lab we are interested in understanding why obesity causes diabetes. Much work has revolved around studying the role of brain insulin and leptin signaling in controlling metabolism in peripheral tissues such as the liver and adipose tissue. Further, we study how adipose tissue function affects neuroinflammation and brain function and how this control is disrupted in obesity, diabetes, and neurodegenerative diseases including Alzheimer’s. We use a number of complex study protocols for the study of metabolic physiology such as euglycemic hyperinsulinemic clamps and indirect calorimetry; we employ transgenic mouse models and study cell signaling at the transcriptional and protein expression levels in a variety of tissues. When we can we try to translate our findings to humans.
Ongoing Research Projects:
• Role of the SNS in the pathophysiology of diabetes and obesity
• CNS control of glucose counterregulation
• Metabolic dysregulation in traumatic brain injury (TBI)
• Role of impaired insulin action (peripheral and central) in Alzheimer’s disease (AD)
• The role of circadian rhythms in metabolic control and cognition
Ongoing Clinical Studies:
• Light, Metabolic Syndrome, and Alzheimer’s Disease
• Metabolic dysregulation in traumatic brain injury (TBI)
• Antibiotics and hypoglycemia