USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Molecular Endocrinology, Diabetes and Metabolism Institute, City of Hope Medical Center, Duarte, CA 91010, USA.
Cells. 2024 Jul 23;13(15):1233. doi: 10.3390/cells13151233.
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 overexpression significantly increases cold-induced adipose tissue beiging; in contrast, decreasing HA by 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, increasing HA could serve as a new approach for recruiting more beige adipocytes to combat metabolic diseases.
脂肪组织米色化是指米色脂肪细胞在经典白色脂肪组织库中出现的过程。米色脂肪细胞消耗化学能量并分泌脂肪因子，如经典的棕色脂肪细胞，以改善全身代谢，这对肥胖和代谢疾病患者有益。冷暴露和β3-肾上腺素能受体（AR）激动剂治疗是增加小鼠米色脂肪细胞的两种常用刺激物；然而，它们的潜在生物学过程是不同的。对腹股沟白色脂肪组织（iWAT）的转录分析表明，细胞外基质（ECM）途径基因的变化是冷暴露特异性的。透明质酸（HA）是一种由几乎所有细胞产生的非硫酸线性多糖，是 ECM 的最常见成分之一。我们发现冷暴露显著增加了 iWAT 的 HA 水平，而β3-AR 激动剂 CL316,243 则没有。通过过表达增加 iWAT 中的 HA 水平可显著增加冷诱导的脂肪组织米色化；相比之下，通过过表达减少 HA（编码一种消化 HA 的透明质酸酶）可显著减少冷诱导的 iWAT 米色化。所有这些数据表明 HA 在促进脂肪组织米色化中起作用，这是冷暴露所特有的。鉴于β3-AR 激动剂在肥胖和代谢疾病的临床试验中的失败，增加 HA 可能成为招募更多米色脂肪细胞来对抗代谢疾病的新方法。
