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Effect of proinflammatory cytokines on mitochondrial function in 3T3‐L1 adipocytes
Author(s) -
Kuzmicic Jovan Paolo,
Hahn Wendy,
Burrill Joel,
Lavandero Sergio,
Bernlohr David
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.565.16
Subject(s) - proinflammatory cytokine , tfam , nrf1 , mitochondrial biogenesis , fis1 , mitochondrial fusion , mitochondrion , tumor necrosis factor alpha , ppargc1a , endocrinology , biology , chemistry , medicine , microbiology and biotechnology , inflammation , immunology , biochemistry , mitochondrial dna , transcription factor , gene , coactivator
To assess the effects of proinflammatory cytokines on mitochondrial function 3T3‐L1 adipocytes were treated with TNFα, IL‐6 or IL‐1β (1 nM, 0–96 h) and evaluated for mitochondrial function as well as mRNA and protein expression. The treatment of 3T3‐L1 adipocytes with inflammatory cytokines induced mitochondrial dysfunction as evidenced by a significant reduction (p<0.05, n=5) in maximal respiratory capacity (uncoupled respiration), increased proton leak, decreased ATP synthesis‐driven respiration, respiratory control ratio and mitochondrial coupling efficiency. In addition, each of the cytokines reduced the NAD + /NADH ratio (p< 0.01, n=3). Each of the cytokines significantly reduced the mRNA expression of PGC1α and TNFα also decreased the mRNA levels of NRF1 and COXIV, suggesting impairment in mitochondrial biogenesis. TNFα significantly reduced (p<0.01, n=4) the level of the mitochondrial fusion protein OPA1 without affecting the mitochondrial fission proteins DRP1 or FIS1. These results indicate that inflammatory cytokines induce mitochondrial dysfunction and changes in mitochondrial biogenesis/dynamics pathways, possibly contributing to the development of insulin resistance and type 2 diabetes. Supported by NIH DK084669 to DAB. JK holds a PhD scholarship from CONICYT Chile and a Fellowship from PABMB/ASBMB Promoting Research Opportunities for Latin American Biochemists.