O-GlcNAc transferase enables AgRP neurons to suppress browning of white fat.

Authors:
Hai-Bin Ruan
Hai-Bin Ruan
United States
Marcelo O Dietrich
Marcelo O Dietrich
Yale University School of Medicine
New Haven | United States
Zhong-Wu Liu
Zhong-Wu Liu
United States
Marcelo R Zimmer
Marcelo R Zimmer
Yale University School of Medicine
New Haven | United States
Dr. Min-Dian Li, PhD
Dr. Min-Dian Li, PhD
Harvard TH Chan School of Public Health
Postdoctoral Fellow
Cellular and Molecular Physiology
Boston, MA | United States
Jay Prakash Singh
Jay Prakash Singh
Yale University School of Medicine
New Haven | United States
Kaisi Zhang
Kaisi Zhang
Yale University School of Medicine
New Haven | United States
Ruonan Yin
Ruonan Yin
Yale University School of Medicine
New Haven | United States

Cell 2014 Oct;159(2):306-17

Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Section of Comparative Medicine, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address:

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2014.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509746PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
October 2014
44 Reads
57 Citations
32.242 Impact Factor

Article Mentions


Provided by Crossref Event Data
f1000
F1000: F1000
October 15, 2014, 8:00 pm EST

Publication Analysis

Top Keywords

agrp neurons
20
tissue browning
12
adipose tissue
12
browning white
12
white fat
12
o-glcnac transferase
8
suppress browning
8
o-glcnac modification
8
browning
6
neurons
5
o-glcnac
5
agrp
5
cellular processes
4
highly dynamic
4
fundamental cellular
4
processes levels
4
levels o-glcnac
4
regulates fundamental
4
browning highly
4
transferase ogt
4

Similar Publications