Insulin signaling in AgRP neurons regulates meal size to limit glucose excursions and insulin resistance
Open Access
- 26 February 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (9), eabf4100
- https://doi.org/10.1126/sciadv.abf4100
Abstract
The importance of hypothalamic insulin signaling on feeding and glucose metabolism remains unclear. We report that insulin acts on AgRP neurons to acutely decrease meal size and thereby limit postprandial glucose and insulin excursions. The promotion of insulin signaling in AgRP neurons decreased meal size without altering total caloric intake, whereas the genetic ablation of the insulin receptor had the opposite effect. The promotion of insulin signaling also decreased the intake of sucrose-sweetened water or high-fat food over standard chow, without influencing food-seeking and hedonic behaviors. The ability of heightened insulin signaling to override the hedonistic consumption of highly palatable high-fat food attenuated the development of systemic insulin resistance, without affecting body weight. Our findings define an unprecedented mechanism by which insulin acutely influences glucose metabolism. Approaches that enhance insulin signaling in AgRP neurons may provide a means for altering feeding behavior in a nutrient-dense environment to combat the metabolic syndrome.Funding Information
- National Health and Medical Research Council
- Diabetes Australia
This publication has 58 references indexed in Scilit:
- Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feedingDiabetologia, 2013
- Deconstruction of a neural circuit for hungerNature, 2012
- Postprandial Administration of Intranasal Insulin Intensifies Satiety and Reduces Intake of Palatable Snacks in WomenDiabetes, 2012
- Rapid, reversible activation of AgRP neurons drives feeding behavior in miceJCI Insight, 2011
- AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without trainingNature Neuroscience, 2011
- Direct Insulin and Leptin Action on Pro-opiomelanocortin Neurons Is Required for Normal Glucose Homeostasis and FertilityCell Metabolism, 2010
- Segregation of Acute Leptin and Insulin Effects in Distinct Populations of Arcuate Proopiomelanocortin NeuronsJournal of Neuroscience, 2010
- Glucose Metabolism In Vivo in Four Commonly Used Inbred Mouse StrainsDiabetes, 2008
- Specific Physiological Roles for Signal Transducer and Activator of Transcription 3 in Leptin Receptor-Expressing NeuronsMolecular Endocrinology, 2008
- Collective and Individual Functions of Leptin Receptor Modulated Neurons Controlling Metabolism and IngestionEndocrinology, 2007