Current Funding Awardees
Pilot and Feasibility Awardees
Alyssa Huang, M.D.
Acting Assistant Professor of Pediatrics
Seattle Children's Hospital
Division of Endocrinology & Diabetes
The Interactions of Disordered Eating Behavior, Glycemic Control, and Adiposity on Hypothalamic Gliosis in Adolescents and Young Adults with Type 1 Diabetes
One in five adolescents and young adults with type 1 diabetes (AYAD) exhibit disordered eating behaviors (DEB)—nearly twice the rate among healthy peers—associated with worse glycemic control, obesity, and higher risk of diabetes-related complications. The mechanisms that drive DEB are not well understood, limiting effective clinical treatment. The mediobasal hypothalamus (MBH) in the central nervous system is a key area of feeding regulation and MBH gliosis is associated with impaired satiety, hyperphagia and glucose dysregulation. It is unknown whether AYAD have hypothalamic gliosis related to DEB, insulin resistance and/or obesity, or if hyperglycemia independently drives the development of MBH gliosis, promoting changes in eating behavior and weight gain. Our study will apply complementary strategies to systematically uncover these complex interrelationships, including the use of non-invasive structural MRI on AYAD females, who have the highest rates of disordered eating behavior.
Jingjing Niu, M.D.
Department of Medicine
Division of Metabolism, Endocrinology & Nutrition
Peri-Islet Glia Identity and Relation to β-Cell Function in Obesity
Peri-islet glial cells (PIGCs) are support cells positioned to control neuron-endocrine-vascular cell communication within the islet; however, little is known about the relationship between PIGCs and islet cell function. It has been suggested that PIGCs increase in number (termed gliosis) following β-cell toxin and autoimmune islet cell injury. Also, glial-cell line-derived neurotrophic factor overexpression promotes β-cell survival and proliferation. Our project aims to determine the relationship between increased PIGCs (via quantification of glia fibrillary acidic protein (GFAP) expression) and β-cell function, and how this is altered in the setting of increased dietary fat. We hypothesize that metabolic stress such as diet-induced obesity promotes the activation/proliferation of PIGCs, and this process is required for the adaptive increase in β-cell function that occurs with increased metabolic demand.
Dick and Julia McAbee Postdoctoral Fellowship Awardee
Nicole Richardson, Ph.D.
Mentors: Jarrad Scarlett and Michael Schwartz
Department of Medicine
Division of Metabolism, Endocrinology, and Nutrition
Regulation of Glucose Homeostasis by Endogenous Hypothalamic Fibroblast Growth Factor 1 (FGF1) Signaling
Obesity and type 2 diabetes (T2D) are major causes of morbidity and mortality worldwide, and recent studies have identified the brain as a target for the treatment of both disorders. As an example, sustained remission of hyperglycemia has been demonstrated across multiple rodent models of T2D following central administration of fibroblast growth factor 1 (FGF1). Our preliminary findings extend this work by showing that 1) FGF1 is expressed in the hypothalamus, and 2) obesity and glucose intolerance result from depletion of endogenous hypothalamic FGF1. In this project, we will quantify hypothalamic FGF1 expression by cell type under varying metabolic conditions and establish the role of endogenous hypothalamic FGF1 signaling regulation of glucose and energy homeostasis, with the hope to identify new avenues for therapeutic development in the treatment of obesity and T2D.
Samuel and Althea Stroum Graduate Fellowship Awardee
Mentor: Jessica Jones-Smith
Department of Epidemiology
Role of Maternal Breast Milk Antibodies on Offspring Metabolism
Breast milk is a key regulator of host-microbiome interactions in early life and breastfeeding in infancy is widely recognized to promote healthy metabolic function later in life, including reducing the risk of type 2 diabetes. We previously identified breast milk antibodies as critical regulators of host-microbiota interactions in offspring, where they serve to blunt microbiota-driven adaptive immune responses. Strikingly, as adults, breast milk antibody-deficient offspring exhibit persistent metabolic alterations, including decreased white adipose tissue mass and impaired glucose homeostasis. We hypothesize that by regulating aberrant immune responses to the microbiota in early life, breast milk antibodies temper the chronic activation of microbiota-specific adaptive immune cells, thereby supporting healthy energy balance and lipid homeostasis. We propose to study the metabolic function of breast milk antibody-deficient pups depleted of activated T cells that arise early in life. Alterations in white adipose tissue can lead to lipid dysfunction. Thus, to understand the impact of breast milk antibodies on white adipose tissue physiology, we propose to evaluate the lipid metabolism in pups sufficient or deficient in breast milk antibodies. Defining the molecular mechanisms by which breastfeeding promotes metabolic health may advance the development of early life interventions that decrease the incidence of comorbidities associated with a lack of breastfeeding, including obesity and diabetes.