The P2X7 ion channel is dispensable for energy and metabolic homeostasis of white and brown adipose tissues

Purinergic signalling

article

Tian Tian¹  Markus Heine¹  Ioannis Evangelakos¹  Michelle Y. Jaeckstein¹  Nicola Schaltenberg¹  Tobias Stähler²  Friedrich Koch-Nolte²  Manju Kumari¹  Joerg Heeren¹ 

[1] Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf;Institute of Immunology, University Medical Center Hamburg-Eppendorf

关键词: Purinergic signaling;    Adipose tissue;    P2X7 ion channel;    Energy metabolism;    Obesity;   

DOI  :  10.1007/s11302-020-09738-7

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

Several studies suggest a role of extracellular adenine nucleotides in regulating adipose tissue functions via the purinergic signaling network. Metabolic studies in mice with global deletion of the purinergic receptor P2X7 on the C57BL/6 background indicate that this receptor has only a minor role in adipose tissue for diet-induced inflammation or cold-triggered thermogenesis. However, recent data show that a polymorphism (P451L) present in C57BL/6 mice attenuates P2X7 receptor function, whereas BALB/c mice express the fully functional P451 allele. To determine the potential role of P2rx7 under metabolic and thermogenic stress conditions, we performed comparative studies using male P2rx7 knockout (KO) and respective wild-type controls on both BALB/c and C57BL/6 backgrounds. Our data show that adipose P2rx7 mRNA levels are increased in obese mice. Moreover, P2rx7 deficiency results in reduced levels of circulating CCL2 and IL6 with a moderate effect on gene expression of pro-inflammatory markers in white adipose tissue and liver of BALB/c and C57BL/6 mice. However, P2X7 expression does not alter body weight, insulin resistance, and hyperglycemia associated with high-fat diet feeding on both genetic backgrounds. Furthermore, deficiency of P2rx7 is dispensable for energy expenditure at thermoneutral and acute cold exposure conditions. In summary, these data show that—apart from a moderate effect on inflammatory cytokines—P2X7 plays only a minor role in inflammatory and thermogenic effects of white and brown adipose tissue even on the BALB/c background.

【 授权许可】

CC BY