Buettner Lab studies mechanisms of central control of peripheral metabolism and how this is altered in metabolic disease. We employ integrated physiology approaches to deconstruct the role of the brain in orchestrating organ crosstalk such as nutrient flux between adipose tissue and the liver and its relevance in regulating insulin action.
We aim to elucidate the role of the sympathetic nervous system (SNS), adipose tissue lipolysis, lipotoxicity, glucose counter-regulation, and neuroinflammation in the pathophysiology of diabetes and obesity. These studies may provide important insights into mechanisms that drive the development and progression of metabolic disease and allow the identification of novel therapeutic approaches for the treatment of obesity and diabetes.
Ongoing Projects
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Role of the SNS in the pathophysiology of diabetes and obesity
We study the role of the SNS in the regulation of adipose tissue and liver function and mechanisms through which chronic dysregulation of catecholamine levels and sympathetic outflow to peripheral metabolic organs can contribute to insulin resistance, hyperglycemia, and systemic inflammation. To this aim, we are developing novel methods to monitor SNS activity in peripheral metabolic organs in real time in vivo and have developed inducible loss of function models to study the function of the SNS.
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CNS control of glucose counterregulation
We are characterizing the physiological role of hypothalamic inflammation in metabolic homeostasis, specifically the role of microglia, the gut-brain axis, and interferon gamma in counterregulation. We aim to determine to what extend dysregulation of counterregulatory mechanisms contributes to insulin resistance in obesity and diabetes.
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Metabolic dysregulation in traumatic brain injury (TBI)
The aim of this project is to study the effect of TBI-induced neuroinflammation in the CNS control of peripheral metabolism as well as the contribution of metabolic dysregulation to chronic neuroinflammation in TBI.
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Role of impaired insulin action (peripheral and central) in Alzheimer’s disease (AD)
As AD is increasingly understood as a neuroinflammatory disease with possibly important metabolic drivers, we wish to examine the role of adipose tissue function and lipotoxicity and brain insulin signaling on cognition and neuroinflammation.
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The role of circadian rhythms in metabolic control and cognition
Circadian rhythms regulate many biological processes such as metabolism and cognition. We are interested to understand how the central clock synchronizes with peripheral clocks, if light exposure can be used to reentrain circadian rhythms in both rodents and humans and if this improves metabolism and cognition.
Clinical Studies
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Light, Metabolic Syndrome, and Alzheimer’s Disease
Dr. Buettner is currently conducting a clinical study to determine whether a long-term tailored light intervention that promotes entrainment can improve sleep disturbances, inflammation, insulin sensitivity, glucose disposal, and cognition in patients with mild cognitive impairment.
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Metabolic dysregulation in traumatic brain injury (TBI)
The aim of this project is to study the effect of TBI-induced neuroinflammation in the CNS control of peripheral metabolism as well as the contribution of metabolic dysregulation to chronic neuroinflammation in TBI. Based on our finding that rodents develop impaired glucose homeostasis after TBI, we are currently conducting a retrospective chart review in collaboration with the Icahn School of Medicine at Mount Sinai to determine the incidence of prediabetes and diabetes in patients with a history of TBI and thus determine the translational relevance of our findings in rodents.
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Antibiotics and hypoglycemia
Preclinical studies in Dr. Buettner’s lab have shown that certain antibiotics, which alter the gut microbiome composition and modulate the inflammatory environment in the hypothalamus, lead to impaired glucose counterregulation to hypoglycemia or neuroglycopenia. The purpose of this study is to assess the translational relevance of our findings in rodents and investigate the association between specific antibiotics and the risk of hypoglycemia in the inpatient population at RWJMS.