Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

Biochim Biophys Acta Gen Subj. 2022 Apr;1866(4):130085. doi: 10.1016/j.bbagen.2022.130085. Epub 2022 Jan 10.

Abstract

Background: Adipose tissue plays a pivotal role in the development and progression of the metabolic syndrome which along with its complications is an epidemic of the 21st century. Irisin is an adipo-myokine secreted mainly by skeletal muscle and targeting, among others, adipose tissue. In brown adipose tissue it upregulates uncoupling protein-1 (UCP1) which is responsible for mitochondrial non-shivering thermogenesis.

Methods: Here we analyzed the effects of irisin on the metabolic activity of 3T3-L1 derived adipocytes through a mitochondrial flux assay. We also assessed the effects of irisin on the intracellular signaling through Western Blot. Finally, the gene expression of ucp1 and lipolytic genes was examined through RT-qPCR.

Results: Irisin affects mitochondrial respiration and lipolysis in a time-dependent manner through the regulation of PI3K-AKT pathway. Irisin also induces the expression of UCP1 and the regulation of NF-κB, and CREB and ERK pathways.

Conclusion: Our data supports the role of irisin in the induction of non-shivering thermogenesis, the regulation of energy expenditure and lipolysis in adipocytes.

General significance: Irisin may be an attractive therapeutic target in the treatment of obesity and related metabolic disorders.

Keywords: Browning; Cell metabolism; Mitochondrial respiration; Signaling; White adipose tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Fibronectins* / genetics
  • Lipolysis*
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Thermogenesis* / genetics

Substances

  • FNDC5 protein, mouse
  • Fibronectins