Ellen Schur has documented evidence of hypothalamic gliosis in humans (based on magnetic resonance imaging), and Dr. This “gliosis” reaction is characteristic of the response to neuron injury and is detectable within days of the change in diet, well in advance of increased body weight.
Thaler now runs his own independent lab at UW) revealed that in rodent models, obesity induced by switching animals from standard chow to consumption of a high-fat diet (HFD) is accompanied by inflammatory activation of two distinct subsets of glial cells – microglia and astrocytes – specifically in the hypothalamic arcuate nucleus (ARC), a key brain area for control of energy balance and glucose homeostasis. Joshua Thaler was completing his training in the Schwartz lab (Dr. Hypothalamic Inflammation Obesity and Type 2 Diabetes This overarching hypothesis is supported in part by work described below. Should defects exist in the ability to mount, sense or respond to these key afferent signals, both body fat content and glucose levels are expected increase, setting in motion a vicious cycle of weight gain, insulin resistance and impaired insulin secretion that can lead to type 2 diabetes. These humoral inputs are sensed in the brain, favoring the return of food intake and glucose production to their original values – in normal individuals.
DANIEL SCHWARTZ MD NORTHWEST HOSPITAL FREE
As body fat content and plasma glucose levels begin to rise, circulating concentrations of leptin, insulin, and free fatty acids increase as well. In turn, the brain activates responses that promote positive energy balance (e.g., increased food intake and decreased energy expenditure) and raise circulating levels of glucose and other nutrients (e.g., increased hepatic glucose production). Conversely, a decrease in neuronal input from one or more of these afferent signals is proposed to alert the brain to a current or pending deficiency of stored energy or nutrient availability. Stated differently, when the brain senses that body energy content and nutrient availability are in sufficient supply, further increases of stored energy (in the form of fat) and circulating nutrients (e.g., glucose) are resisted. Specifically, our work centers on the concept that in times of plenty (i.e., ample fat stores and food availability), input to key brain areas from relevant afferent signals (e.g., insulin, leptin and free fatty acids) leads to inhibition of both energy intake and endogenous glucose production, while simultaneously increasing energy expenditure and mobilizing fat stores. An extension of this hypothesis is that defects in this central control system are implicated in the link between obesity, insulin resistance and type 2 diabetes. Schwartz’s research program is to investigate the hypothesis that the brain plays an essential role to promote homeostasis of both energy balance and glucose metabolism in response to afferent input from adiposity- and nutrient-related signals. Role of the Brain in the Pathogenesis of Obesity, Insulin Resistance and Type 2 DiabetesĪ major focus of Dr. Schwartz’s research focuses on hypothalamic and neuroendocrine control of energy balance and glucose metabolism, and on CNS mechanisms involved in obesity, insulin resistance and diabetes.
He is also former director of the Nutrition Obesity Research Center (NORC) at UW.ĭr. He serves as Director of the UW Medicine Diabetes Institute, is a member of the American Society for Clinical Investigation and the Association of American Physicians, is the recipient of numerous awards and serves on several editorial boards. Schwartz has been continuously funded by the NIH and other sources to study brain mechanisms governing body weight regulation, glucose homeostasis, obesity and diabetes for over 25 years, with >250 publications in these areas. In addition to many years of clinical teaching and patient care at Harborview Medical Center in Seattle, Dr. Daniel Porte, Jr., at UW, was completed in 1990. His fellowship training in Endocrinology and Metabolism, undertaken in the lab of Dr. Schwartz received his MD from Rush Medical College in 1983 and completed his residency in Medicine at UW in 1986. Professor of Medicine, Division of Metabolism, Endocrinology and Nutritionĭr.Visit the Schwartz Laboratory Michael Schwartz, MDĮmail: Co-Director, UW Medicine Diabetes Institute
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