Sucrose overconsumption impairs AgRP neuron dynamics and promotes palatable food intake

Carolyn M. Lorch; Nikolas W. Hayes; Jessica L. Xia; Stefan W. Fleps; Hayley E. McMorrow; Haley S. Province; Joshua A. Frydman; Jones G. Parker; Lisa R. Beutler

doi:10.1016/j.celrep.2024.113675

Sucrose overconsumption impairs AgRP neuron dynamics and promotes palatable food intake

Carolyn M. Lorch, Nikolas W. Hayes, Jessica L. Xia, Stefan W. Fleps, Hayley E. McMorrow, Haley S. Province, Joshua A. Frydman, Jones G. Parker, Lisa R. Beutler^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

Rapid gut-brain communication is critical to maintain energy balance and is disrupted in diet-induced obesity. In particular, the role of carbohydrate overconsumption in the regulation of interoceptive circuits in vivo requires further investigation. Here, we report that an obesogenic high-sucrose diet (HSD) selectively blunts silencing of hunger-promoting agouti-related protein (AgRP) neurons following intragastric delivery of glucose, whereas we previously showed that overconsumption of a high-fat diet (HFD) selectively attenuates lipid-induced neural silencing. By contrast, both HSD and HFD reversibly dampen rapid AgRP neuron inhibition following chow presentation and promote intake of more palatable foods. Our findings reveal that excess sugar and fat pathologically modulate feeding circuit activity in both macronutrient-dependent and -independent ways and thus may additively exacerbate obesity.

Original language	English (US)
Article number	113675
Journal	Cell reports
Volume	43
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2024.113675
State	Published - Feb 27 2024

Funding

We recognize the Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by NCI P30-CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center , for processing mouse liver specimens for histology. We acknowledge Ms. Jiao-Jing Wang from the Northwestern University Microsurgery and Preclinical Research Core for performing a liver function panel using mouse plasma specimens. BioRender was used to prepare the graphical abstract. We thank Dr. Joseph Bass for providing feedback on the manuscript. L.R.B. acknowledges support from the American Diabetes Association Pathway to Stop Diabetes Award ( 12-22-ACE-31 ). This work was also supported by NIH grants P30-DK020595 , K08-DK118188 , and R01-DK128477 (L.R.B.) and T32-HL134633 (C.M.L.).

Keywords

AgRP neurons
CP: Neuroscience
carbohydrates
gut-brain axis
metabolism
obesity
sugar-sweetened beverages

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2024.113675

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title = "Sucrose overconsumption impairs AgRP neuron dynamics and promotes palatable food intake",

abstract = "Rapid gut-brain communication is critical to maintain energy balance and is disrupted in diet-induced obesity. In particular, the role of carbohydrate overconsumption in the regulation of interoceptive circuits in vivo requires further investigation. Here, we report that an obesogenic high-sucrose diet (HSD) selectively blunts silencing of hunger-promoting agouti-related protein (AgRP) neurons following intragastric delivery of glucose, whereas we previously showed that overconsumption of a high-fat diet (HFD) selectively attenuates lipid-induced neural silencing. By contrast, both HSD and HFD reversibly dampen rapid AgRP neuron inhibition following chow presentation and promote intake of more palatable foods. Our findings reveal that excess sugar and fat pathologically modulate feeding circuit activity in both macronutrient-dependent and -independent ways and thus may additively exacerbate obesity.",

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AU - Hayes, Nikolas W.

AU - Xia, Jessica L.

AU - Fleps, Stefan W.

AU - McMorrow, Hayley E.

AU - Province, Haley S.

AU - Frydman, Joshua A.

AU - Parker, Jones G.

AU - Beutler, Lisa R.

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N2 - Rapid gut-brain communication is critical to maintain energy balance and is disrupted in diet-induced obesity. In particular, the role of carbohydrate overconsumption in the regulation of interoceptive circuits in vivo requires further investigation. Here, we report that an obesogenic high-sucrose diet (HSD) selectively blunts silencing of hunger-promoting agouti-related protein (AgRP) neurons following intragastric delivery of glucose, whereas we previously showed that overconsumption of a high-fat diet (HFD) selectively attenuates lipid-induced neural silencing. By contrast, both HSD and HFD reversibly dampen rapid AgRP neuron inhibition following chow presentation and promote intake of more palatable foods. Our findings reveal that excess sugar and fat pathologically modulate feeding circuit activity in both macronutrient-dependent and -independent ways and thus may additively exacerbate obesity.

AB - Rapid gut-brain communication is critical to maintain energy balance and is disrupted in diet-induced obesity. In particular, the role of carbohydrate overconsumption in the regulation of interoceptive circuits in vivo requires further investigation. Here, we report that an obesogenic high-sucrose diet (HSD) selectively blunts silencing of hunger-promoting agouti-related protein (AgRP) neurons following intragastric delivery of glucose, whereas we previously showed that overconsumption of a high-fat diet (HFD) selectively attenuates lipid-induced neural silencing. By contrast, both HSD and HFD reversibly dampen rapid AgRP neuron inhibition following chow presentation and promote intake of more palatable foods. Our findings reveal that excess sugar and fat pathologically modulate feeding circuit activity in both macronutrient-dependent and -independent ways and thus may additively exacerbate obesity.

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Sucrose overconsumption impairs AgRP neuron dynamics and promotes palatable food intake

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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