HCBP6-induced activation of brown adipose tissue and upregulated of BAT cytokines genes

J Therm Biol. 2022 Oct:109:103306. doi: 10.1016/j.jtherbio.2022.103306. Epub 2022 Aug 29.

Abstract

Brown adipose tissue is a thermogenic organ, which consumes chemical energy as heat to protect animals from low temperature and metabolic diseases. However, the role and mechanism of the new factor that up-regulates the heat-generating capacity of brown adipose tissue is still unclear. Here, we found that hepatitis C virus core binding protein 6 (HCBP6), as a key regulator gene in the homeostasis of liver lipid metabolism, is an important enhancer for activating brown fat to ensure thermogenesis. HCBP6 upregulates the expression of UCP1 and increases the number of mitochondria in brown adipocytes. In the BAT of HCBP6-knockout mice induced by a high-fat diet, UCP1 and BAT activity-related genes Pgc1α, Cidea and oxidation phosphorylation-related genes (OXPHOS) were significantly reduced. In addition, the transcriptomics results show that the loss of HCBP6 caused disorder of the metabolic pathway, the expression of brown adipocyte development genes was significantly reduced, and the expression of most BAT cytokine genes was reduced. In conclusion, HCBP6 increased ucp1-dependent thermogenesis in BAT and improved liver lipid metabolism, possibly by enhancing the activity of brown fat and changing the expression of BAT cytokine genes.

Keywords: Brown adipose tissue; Cytokine; HCBP6; UCP1.

MeSH terms

  • Adipocytes, Brown / metabolism
  • Adipose Tissue, Brown* / metabolism
  • Animals
  • Cytokines / genetics
  • Mice
  • Mice, Knockout
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Thermogenesis* / genetics
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism

Substances

  • Cytokines
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Uncoupling Protein 1