Yunlei Yang, M.D., Ph.D.

Research Focus

Our laboratory investigates the central and peripheral mechanisms that regulate energy metabolism, glucose homeostasis, and affective behaviors. By integrating advanced neuroscience approaches with metabolic phenotyping, we seek to define how neurons, glial cells, and neural circuits coordinate physiological and behavioral states in health and disease.

Research Interests

1. Glial regulation of adipose tissue metabolism and glucose homeostasis
Although neuronal mechanisms controlling food intake, body weight, adipose tissue metabolism, and glucose homeostasis have been extensively studied, the contributions of non-neuronal glial cells remain incompletely understood. Our recent work demonstrates that astrocytes regulate neuronal synaptic plasticity and feeding behavior and metabolism. We are now investigating whether and how astrocytes and other glial cells in the central and peripheral nervous systems regulate adipocyte function, lipid metabolism, and systemic glucose homeostasis. To address these questions, we combine cell-type-specific chemogenetic and optogenetic manipulations, fiber photometry, electrophysiology, transgenic mouse models, and assays of adipose tissue metabolism and glucose regulation. These approaches provide the anatomical, cellular, and temporal resolution needed to uncover previously unrecognized glia–neuron–adipocyte interactions that influence whole-body metabolic homeostasis.

2. Neural circuits controlling adipose tissue lipid metabolism
Our previous studies showed that energy deficit and the hunger-promoting hormone ghrelin increase excitatory synaptic strength and action-potential firing in orexigenic agouti-related peptide (AgRP) neurons within the arcuate nucleus of the hypothalamus. These findings support an important role for synaptic plasticity in enabling hypothalamic neurons to integrate metabolic signals and regulate feeding behavior. Building on this work, we aim to identify and characterize the neuronal populations and projection-defined circuits that control adipose tissue lipolysis, thermogenesis, and systemic energy balance. We use cell-type- and circuit-specific chemogenetics and optogenetics, fiber photometry, single-cell RT-qPCR and RNA sequencing, neurochemical measurements, and comprehensive metabolic assays to determine how defined neural pathways coordinate feeding with adipose tissue function.

3. Mechanisms underlying obesity- and diabetes-associated affective behaviors
We are also interested in the bidirectional interactions between metabolic state and affective behaviors, including anxiety- and depression-related behaviors. Obesity and diabetes are frequently associated with psychiatric disorders, creating a substantial and growing public health burden. We have observed anxiety- and depression-like phenotypes in mouse models of obesity and diabetes. Our current research seeks to identify the neuronal populations, glial mechanisms, and neural circuits responsible for these behavioral changes. By defining how metabolic dysfunction alters brain activity and behavior, we aim to uncover mechanistic links between metabolic and neuropsychiatric disorders and identify potential targets for therapeutic intervention.

Yang Y, Atasoy D, Su HH, Sternson SM (2011) Hunger states switch a flip-flop memory circuit via a synaptic AMPK-dependent positive feedback loop. Cell. 146(6):992-1003. PMID:21925320. Featured in Cell and Cell Metabolism.

Tian L, Yang Y, Wysocki LM, Arnold AC, Hu A, Ravichandran B, Sternson SM, Looger LL, Lavis LD (2012) Selective esterase-ester pair for targeting small molecules with cellular specificity. Proc Natl Acad Sci U S A. 109(13):4756-61. PMID:22411832. Featured in Faculty 1000Prime.

Yang L, Qi Y, Yang Y* (2015) Astrocytes control food intake by inhibiting AGRP neuron activity via adenosine A1 receptors. Cell Reports. 11(5):798-807 PMID: 25921535. Highlighted in Cell press.

Yang Y, Lee P, Sternson SM (2015) Cell type-specific pharmacology of NMDA receptors using masked MK801. eLife. 4. doi:10.7554/eLife.10206. PMID: 26359633.

Qi Y, Yang Y* (2015) Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors. Journal of Neuroscience. 35(38):13171-82. PMID: 26400946.

Sweeney P, Yang Y* (2015) An excitatory ventral hippocampus to lateral septum circuit that suppresses feeding. Nature Communications. 6:10188. doi: 10.1038/ncomms10188. PMID: 26666960. Featured in Faculty 1000Prime.

Sweeney P, Qi Y, Xu Z, Yang Y* (2016) Activation of hypothalamic astrocytes suppresses feeding without altering emotional states. GLIA. 64(12):2263-2273. PMID:27658520.

Sweeney P, Yang Y* (2016) An Inhibitory Septum to Lateral Hypothalamus Circuit That Suppresses Feeding. Journal of Neuroscience. 36(44):11185-11195. PMID:27807162. Featured Article.

Sweeney P, Li C, Yang Y* (2017) Appetite suppressive role of medial septal glutamatergic neurons. Proc Natl Acad Sci U S A. 114(52):13816-13821. PMID:29229861 Highlighted in Nature.

Sweeney P, Yang Y* (2017) Neural Circuit Mechanisms Underlying Emotional Regulation of Homeostatic Feeding. Trends Endocrinol Metab. 28(6):437-448. Review. PMID:28279562.

Li C, Hou Y, Zhang J, Sui G, Du X, Licinio J, Wong ML, Yang Y* (2019) AGRP neurons modulate fasting-induced anxiolytic effects. Translational Psychiatry. 9(1):111. PMID:30850579.

Zhang J, Chen D, Sweeney P, Yang Y* (2020) An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake. Nature Communications. 11(1):6326. PMID:33303759.

Huang T, Guan F, Licinio J, Wong ML, Yang Y* (2021) Activation of septal OXTr neurons induces anxiety- but not depressive-like behaviors. Molecular Psychiatry. 26(12):7270-7279. PMID:34489531. Highlighted in AMUZA.

Zhang J, Hou Y, Du XL, Chen D, Sui G, Qi Y, Licinio J, Wong ML, Yang Y* (2021) ADORA1-driven brain-sympathetic neuro-adipose connections control body weight and adipose lipid metabolism. Molecular Psychiatry. 26(7):2805-2819. PMID:33067580.

Chen D, Qi Y, Zhang J, Yang Y* (2022) Deconstruction of a hypothalamic astrocyte-white adipocyte sympathetic axis that regulates lipolysis in mice. Nature Communications. 13(1):7536. PMID:36477150.

Liu SM, et al. (2023) The gut signals to AGRP expressing cells of the pituitary to control glucose homeostasis. J Clin Invest 133(7):e164185. PMID:36787185.

Chen D, Yang YY, Yang Y* (2025) Astrocyte loss augments body weight through reduction in adipose sympathetic outflows. GLIA 73(5):1068-1076. PMID:39780483.

Min H, Yang YY, Yang Y* (2025) Cold induces brain region-selective cell activity-dependent lipid metabolism. eLife 13:RP98353. PMID:39882847.

Min H, Zheng Q, Yang Y* (2026) Projection-defined hypothalamic outputs differentially regulate thermogenesis and lipolysis. Proc Natl Acad Sci U S A. 123(22):e2535878123. PMID:42201977.

Zheng Q, Yang Y* (2026) Peripheral neural adenosine A1 receptors retrain brown adipose thermogenesis. In revision.