1. Academic Validation
  2. Glycogen synthesis is required for adaptive thermogenesis in beige adipose tissue and affects diet-induced obesity

Glycogen synthesis is required for adaptive thermogenesis in beige adipose tissue and affects diet-induced obesity

  • Am J Physiol Endocrinol Metab. 2024 Apr 3. doi: 10.1152/ajpendo.00074.2024.
Shixuan Zhuo 1 Meijuan Bai 2 Zinan Wang 1 Lingling Chen 1 Zixuan Li 1 Jinzhu Chen 1 Xiaoyi Ye 1 Cheng Guo 1 Yan Chen 3
Affiliations

Affiliations

  • 1 Chinese Academy of Sciences, China.
  • 2 Physiology, The University of Texas Southwestern Medical Center, Dallas, United States.
  • 3 Chinese Academy of Sciences, Shanghai, China.
Abstract

Glycogen is a form of energy storage for glucose in different tissues such as liver and skeletal muscle. It remains incompletely understood how glycogen impacts on adipose tissue functionality. Cold exposure elevated the expression of Gys1 which encodes glycogen synthase 1 in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT). The in vivo function of Gys1 was analyzed using a mouse model in which Gys1 was deleted specifically in adipose tissues. Under normal chow conditions, Gys1 deletion caused little changes to body weight and glucose metabolism. Deletion of Gys1 abrogated upregulation of UCP1 and other thermogenesis-related genes in iWAT upon prolonged cold exposure or treatment with b3-adrenergic receptor agonist CL-316,243. Stimulation of UCP1 by CL-316,243 in adipose-derived stromal cells (SVFs) was also reduced by Gys1 deletion. Both the basal glycogen content and CL-316,243-stimulated glycogen accumulation in adipose tissues were reduced by Gys1 deletion. High-fat diet-induced obesity and Insulin resistance were aggravated in Gys1-deleted mice. The loss of body weight upon CL-316,243 treatment was also abrogated by the loss of Gys1. In conclusion, our results underscore the pivotal role of glycogen synthesis in adaptive thermogenesis in beige adipose tissue and its impact on diet-induced obesity in mice.

Keywords

adipose tissue; glycogen; obesity; thermogenesis.

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