The Scarlett laboratory investigates the integrated mechanisms whereby the brain and periphery regulation glucose and energy homeostasis and identifying how defects in this system contribute to diabetes and obesity pathogenesis. Recent work in the field of diabetes research supports the concept of a brain-centered glucoregulatory system that works cooperatively with the pancreatic islets, liver and intestines to regulate blood glucose. The current focus of the lab centers on the recently reported finding that the brain is a target for the fibroblast growth factor (FGF), FGF1, and that in response to central FGF1 administration that the brain can promote sustained glucose lowering in murine models of obesity and diabetes. Specifically, our current studies are focused on elucidating the specific central neurocircuits, receptors and intracellular signaling pathways that are targeted by central FGF1 therapy. A second set of studies examines the peripheral mechanisms that underlie the glucose-lowering effect of brain FGF1 signaling, specifically focusing on mechanisms whereby basal glucose clearance is increased due to increased hepatic glucose uptake and pancreatic islet function. A final line of research relates to integrins, which, although recently implicated in the control of insulin sensitivity in peripheral tissues, have not previously been a focus of studies investigating brain control of glucose homeostasis. Ultimately, the overarching goal of this research is to achieve an improved understanding of the central and peripheral mechanisms that control glucose and energy homeostasis to support the development of new, more effective treatment options for diabetes and obesity.
News
Chelsea Faber, Jennifer Deem, Michael Schwartz, Jarrad Scarlett & Gregory Morton published in eLife.
UWMDI postdoctoral fellow, Chelsea Faber, PhD, is first author on a manuscript entitled “Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism” that also includes UWMDI co-authors Jennifer Deem, PhD, Jarrad Scarlett, MD, PhD, Michael Schwartz, MD and senior author, Gregory Morton, PhD. An improved understanding of the neurocircuits that couple circadian systems to energy homeostasis will facilitate the development of new strategies for the treatment of obesity.
Jarrad Scarlett, MD, PhD receives UW Royalty Research Fund award
Dr. Jarrad Scarlett, MD, PhD, has been awarded a 1-year grant through the UW Royalty Research Fund for his project “Mechanisms of central FGF1 remission of diabetic hyperglycemia.” The goal of this project is to begin to elucidate the central and peripheral mechanisms of FGF1 action in the brain to normalize glycemia in rodent models of T2D in a sustained manner, and inform new approaches to diabetes treatment.
Jennifer Deem, PhD, and Co-Author Jarrad Scarlett, MD, PhD Published in the Journal Elife
UWMDI Acting Instructor of Medicine, Jennifer Deem, PhD, is a first author on a manuscript entitled “Cold-induced hyperphagia requires AgRP-neuron activation in mice” in the journal Elife that also includes UWMDI co-authors Chelsea Faber, PhD, Jarrad Scarlett, MD, PhD, Michael Schwartz, MD and senior author, Gregory Morton, PhD. Using state-of-the-art neuroscience approaches, this work establishes a physiologically important role for neurons in the hypothalamus that express agouti-related peptide (AgRP) in the feeding response to cold exposure. The identification of the neurocircuits that link thermoregulation to AgRP neurons and the control of food intake has the potential to identify novel strategies for the treatment of obesity.
Gregory Morton, PhD, with Co-Investigators Michael Schwartz, MD, Jarrad Scarlett, MD, PhD, receive NIH R01 award
Dr. Gregory Morton has been awarded an NIH R01 for his project entitled “Thermoregulatory circuits that regulate feeding”. This 4-year award, totaling $2,097,213, seeks to advance the understanding of the neurocircuitry linking thermoregulation to Agrp neurons and feeding and may identify novel strategies for the treatment of obesity by blunting the associated hyperphagic response. Co-investigators on this project include UWMDI researchers Michael Schwartz, MD and Jarrad Scarlett, MD, PhD.
Michael Schwartz, MD, with Co-Investigators Gregory Morton, PhD, Jarrad Scarlett, MD, PhD, Awarded Novo Nordisk Research Agreement
Dr. Michael Schwartz has received a $1M research grant with Novo Nordisk. This two-year project seeks to identify neurons in the brain that detect and respond to changes of the circulating glucose level and determine their roles in glucose homeostasis. Co-investigators on the project are UWMDI researchers Gregory Morton, PhD and Jarrad Scarlett, MD, PhD. Dr. Schwartz is the RH Williams Endowed Chair in Medicine and a Professor in the Division of Metabolism, Endocrinology and Nutrition.
Dr. Michael Schwartz, MD, and Co-Author Jarrad Scarlett, MD, PhD Published in Nature Metabolism.
Dr. Michael Schwartz, MD, is senior author of: “Perineuronal net formation during the critical period for neuronal maturation in the hypothalamic arcuate nucleus” in Nature Metabolism. UWMDI co-authors are Drs. Jarrad Scarlett, MD, PhD and Kimberly Alonge, PhD and graduate student Jenny Brown.
