O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat
Open accessAbstract
Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here, we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting.
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AGRP neurons have been associated with the negative regulation of energy expenditure.
“AGRP neurons have also been associated with the negative regulation of energy expenditure36–38.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [38]
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Self-citationInsulin Action in AgRP-Expressing Neurons Is Required for Suppression of Hepatic Glucose Production
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Self-citation
- Authors
- Ruan, H.-B., Dietrich, M. O., Liu, Z.-W., Zimmer, M. R., Li, M.-D., Singh, J. P., Zhang, K., Yin, R., Wu, J., Horvath, T. L., & Yang, X.
- Affiliations
- Yale University (US)
- Universidade Federal do Rio Grande do Sul (BR)
- Corresponding author
- Yang, Xiaoyong
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2014-10
- Volume
- 159
- Issue
- 2
- Pages
- 306-317
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4509746
- OpenAlex
- W2061999440
- Cited by
- 281
- References
- 10
- Citations by year
- 2026: 4 · 2025: 15 · 2024: 18 · 2023: 31 · 2022: 24 · 2021: 30 · 2020: 22 · 2019: 27 · 2018: 31 · 2017: 29 · 2016: 27 · 2015: 19 · 2014: 3
- FWCI
- 16.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Repository of the Academy's Library (Library of the Hungarian Academy of Sciences) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Diabetes Association
- Ellison Medical Foundation
- American Heart Association
- University of Louisville
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- National Institutes of Health (DP1OD006850, DP1 DK006850)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089098, DP1DK098058, P30DK034989)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- O-GlcNAc transferase, O-GlcNAcylation, AgRP neurons, hypothalamus, white adipose tissue browning, beige fat, fasting, thermogenesis, diet-induced obesity, insulin resistance, neuronal excitability, voltage-gated potassium channels, energy metabolism
- MeSH terms
- Animals, Adipose Tissue, Brown, Diet, Fasting, Female, Hypothalamus, Insulin Resistance, Male, Mice, Inbred C57BL, Neurons, Obesity, N-Acetylglucosaminyltransferases, Mice, Knockout, Adipose Tissue, White, Agouti-Related Protein, Ghrelin
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