Obesity Causes Selective and Long-lasting Desensitization of AgRP Neurons to Dietary Fat

Overview

Journal Elife

Specialty Biology

Date 2020 Jul 29

PMID 32720646

Citations 48

Authors

Lisa R Beutler

Timothy V Corpuz

Jamie S Ahn

Seher Kosar

Weimin Song

Yiming Chen

Zachary A Knight

Affiliations

Soon will be listed here.

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.

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