Different proinflammatory cytokines control the dynamics, oxidative stress, and metabolism of adipocyte mitochondria.
Insulin resistance, the precursor of type 2 diabetes mellitus, has been mechanistically related to macrophage infiltration of adipose tissue and continuous low-grade generation of inflammatory cytokines. In this investigation, we used the 3T3-L1 model cell system to assess the long-term effects of TNF, IL-6, and IL-1 on adipocyte mitochondrial metabolism and morphology. An increase in proton leak, a decrease in membrane potential, an increase in basal respiration, and a decrease in ATP turnover were all caused by the TNF treatment of cultured adipocytes. While IL-6 and IL-1 lowered maximum respiratory capacity, they exhibited different impacts on ATP turnover, proton leak, and baseline respiration and had no effect on membrane potential.
Only TNF treatment increased oxidative stress (as indicated by protein carbonylation and superoxide anion generation) and C16 ceramide formation in 3T3-L1 cells. When 3T3-L1 adipocytes were treated with cytokines, the mRNA expression of several important transcription factors and regulatory proteins involved in mitochondrial biogenesis, including PGC1 and eNOS, as well as COXIV and Cyt CCyt C, was reduced. TNF solely caused mitochondrial fragmentation, lowered the total level of Opa1 while increased Opa1 cleavage, and had no influence on the expression of levels of mitofusin 2, DRP1, or mitofilin. Each cytokine had effects on the expression of mitochondrial markers. Overall, our findings show that inflammatory cytokines affect adipocyte metabolism differently and specifically, although they all result in reduced mitochondrial activity and a re-programming of fat cell biology.
Learn more about cytokine here:
https://brainly.com/question/14308447
#SPJ4
