Hyaluronan mediates cold-induced adipose tissue beiging

Authors: CHEN, XI - Children'S Nutrition Research Center (CNRC); WANG, YIFAN - City Of Hope National Medical Center; LI, HUIQIAO - Children'S Nutrition Research Center (CNRC); DENG, YANRU - Children'S Nutrition Research Center (CNRC); GIANG, CHARLISE - Children'S Nutrition Research Center (CNRC); SONG, ANYING - City Of Hope National Medical Center; LIU, YU'E - Tongji University; WANG, QIONG - City Of Hope National Medical Center; ZHU, YI - Children'S Nutrition Research Center (CNRC)

Submitted to: Cells
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/19/2024
Publication Date: 7/23/2024
Citation: Chen, X., Wang, Y., Li, H., Deng, Y., Giang, C., Song, A., Liu, Y., Wang, Q.A., Zhu, Y. 2024. Hyaluronan mediates cold-induced adipose tissue beiging. Cells. 13(15). Article 1233. https://doi.org/10.3390/cells13151233.
DOI: https://doi.org/10.3390/cells13151233

Interpretive Summary: Scientists found that when mice get cold, their fat makes more of a sticky sugar called hyaluronan (HA). This sugar helps turn regular fat (which stores energy) into "beige fat," which burns energy to keep the body warm—like a natural heater! The study suggests that boosting HA could help fight obesity by making fat burn calories instead of storing them.

Technical Abstract: Adipose tissue beiging refers to the process by which beige adipocytes emerge in classical white adipose tissue depots. Beige adipocytes dissipate chemical energy and secrete adipokines, such as classical brown adipocytes, to improve systemic metabolism, which is beneficial for people with obesity and metabolic diseases. Cold exposure and ß3-adrenergic receptor (AR) agonist treatment are two commonly used stimuli for increasing beige adipocytes in mice; however, their underlying biological processes are different. Transcriptional analysis of inguinal white adipose tissue (iWAT) has revealed that changes in extracellular matrix (ECM) pathway genes are specific to cold exposure. Hyaluronic acid (HA), a non-sulfated linear polysaccharide produced by nearly all cells, is one of the most common components of ECM. We found that cold exposure significantly increased iWAT HA levels, whereas the ß3-AR agonist CL316,243 did not. Increasing HA levels in iWAT by Has2 overexpression significantly increases cold-induced adipose tissue beiging; in contrast, decreasing HA by Spam1 overexpression, which encodes a hyaluronidase that digests HA, significantly decreases cold-induced iWAT beiging. All these data implicate a role of HA in promoting adipose tissue beiging, which is unique to cold exposure. Given the failure of ß3-AR agonists in clinical trials for obesity and metabolic diseases, increasing HA could serve as a new approach for recruiting more beige adipocytes to combat metabolic diseases.