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Updated: Jan 22, 2026

Self-Administration of Drugs in Mouse Models of Feeding and Obesity
Published on: June 8, 2021
Obesity remodels activity and transcriptional state of a lateral hypothalamic brake on feeding
Mark A Rossi1, Marcus L Basiri1, Jenna A McHenry1
1Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA.
Abstract:
The current obesity epidemic is a major worldwide health concern. Despite the consensus that the brain regulates energy homeostasis, the neural adaptations governing obesity are unknown. Using a combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations of the lateral hypothalamic area (LHA)-a highly conserved brain region that orchestrates feeding-in a mouse model of obesity. The transcriptional profile of LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative of altered neuronal activity. Encoding properties of individual LHA glutamatergic neurons were then tracked throughout obesity, revealing greatly attenuated reward responses. These data demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.
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