Yang Le Lab Projects

The sense of smell mainly plays a priming role in eating behavior. In our recent work (Nature Communications, 2025), we demonstrated that relatively long-time food (chow)-derived odor exposure suppresses food intake in mice and unraveled an olfactory bulb (OB)-originated neural circuits that mediate food-derived odor-induced hypophagia. Future work will aim to uncover the cellular and molecular mechanism underlying long-time food odor exposure-induced hypophagia.

Tanycytes are glial-like cells lining the third ventricle and are increasingly recognized as key components of hypothalamic networks regulating body weight and energy balance. We found that Sox9,  a transcriptional factor, is significantly increased in mice fed with the high-fat diet. Knocking out Sox9 in the hypothalamic tanycytes ameliorates diet-induced obesity. The purpose of this project is to elucidate the mechanism by which Sox9 in hypothalamic tanycytes regulates energy homeostasis. 

Exercise is a powerful physiological intervention that protects against obesity and obesity-associated metabolic diseases, but the mechanisms are incompletely understood. Our previous work (Nature, 2022) found that an exercise-induced metabolite, N-lactoyl-phenylalanine (Lac-Phe), suppresses feeding and obesity.  In an collaborative work (Nature Metabolism, 2025), we further unraveled that Lac-Phe inhibits AgRP neurons in the accurate nucleus of the hypothalamus(ARH) via activation of the KATP channel to suppress feeding. Building on these findings, our current research in my lab focuses on elucidating the molecular mechanisms by which Lac-Phe modulates hypothalamic neural networks to regulate feeding behavior.

During exercise, body temperature naturally rises, and this effect is further amplified in high ambient temperatures. Preventing excessive increases in body temperature is crucial for survival for many species, including humans, as overheating can lead to severe complications such as heatstroke or even organ damage. To counteract the risk of hyperthermia, both behavioral and physiological responses would occur, such as reducing running duration and promoting vasodilation to dissipate heat. However, the neural mechanisms that regulate these thermoregulatory responses during exercise remain largely unknown. In this project, we identified a specific cluster of neurons that are activated during treadmill running, with activation levels positively correlating with body temperature. Further investigation revealed that re-activating these neurons reduces body temperature, enhances vasodilation, and promotes fatigue in mice. We are currently exploring the underlying circuitry and molecular mechanisms governing this thermoregulatory pathway. This work will uncover a novel interoceptive mechanism by which exercise-responsive neurons orchestrate thermoregulatory responses during physical activity, providing insights for understanding the biological basis of thermoregulation during physical activity 

Fundings: TCH scholar seed fund; NIH/NIDDK_R01DK140538 (2024-2029)