Obesity causes selective and long-lasting desensitization of agrp neurons to dietary fat

Lisa R. Beutler, Timothy V. Corpuz, Jamie S. Ahn, Seher Kosar, Weimin Song, Yiming Chen, Zachary A. Knight*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Body weight is regulated by interoceptive neural circuits that track energy need, but how the activity of these circuits is altered in obesity remains poorly understood. Here we describe the in vivo dynamics of hunger-promoting AgRP neurons during the development of diet-induced obesity in mice. We show that high-fat diet attenuates the response of AgRP neurons to an array of nutritionally-relevant stimuli including food cues, intragastric nutrients, cholecystokinin and ghrelin. These alterations are specific to dietary fat but not carbohydrate or protein. Subsequent weight loss restores the responsiveness of AgRP neurons to exterosensory cues but fails to rescue their sensitivity to gastrointestinal hormones or nutrients. These findings reveal that obesity triggers broad dysregulation of hypothalamic hunger neurons that is incompletely reversed by weight loss and may contribute to the difficulty of maintaining a reduced weight.

Original languageEnglish (US)
Article numbere55909
Pages (from-to)1-21
Number of pages21
JournaleLife
Volume9
DOIs
StatePublished - Jul 2020
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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