Federal Project Grant Award Summary

The University of Washington received a $888,773 Project Grant award from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), effective April 15, 2026, with a completion date of January 31, 2031. This biomedical research project investigates the mechanistic contributions of hypothalamic microglia and perineuronal nets (PNNs)—specialized extracellular matrix structures—to obesity pathogenesis. The research examines how diet-induced obesity triggers inflammatory activation of microglia in the arcuate nucleus, a brain region critical for food intake and body weight regulation, and how this activation correlates with loss of PNNs that normally regulate neuron activity in energy homeostasis pathways.

The primary deliverable under this award is foundational scientific research aimed at elucidating the interrelated mechanisms by which microglia activation and PNN loss contribute to obesity development while paradoxically improving glucose tolerance in high-fat diet conditions. The project employs experimental approaches including microglia ablation and silencing studies, analysis of neuropeptide signaling in arcuate nucleus neurons (particularly AGRP and POMC neurons), and investigation of PNN stability under varying inflammatory conditions. Expected outcomes include peer-reviewed publications, mechanistic insights into obesity etiology, and identification of potential therapeutic targets for intervention in diet-induced obesity and related metabolic disorders.