Hyaluronan Mediates Cold-Induced Adipose Tissue Beiging

Several human studies show positive signals, while research methods and sample sizes continue to develop.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 β3-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 β3-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 β3-AR agonists in clinical trials for obesity and metabolic diseases, incr

Evidence level

Several human studies show positive signals, while research methods and sample sizes continue to develop.

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