Biochemistry (Moscow)

, Volume 84, Issue 5, pp 553–561 | Cite as

Chemical Inducers of Obesity-Associated Metabolic Stress Activate Inflammation and Reduce Insulin Sensitivity in 3T3-L1 Adipocytes

  • I. S. StafeevEmail author
  • S. S. Michurina
  • N. V. Podkuychenko
  • M. Y. Menshikov
  • Ye. V. Parfyonova
  • A. V. VorotnikovEmail author


Obesity is accompanied by dyslipidemia, hypoxia, endoplasmic reticulum (ER) stress, and inflammation, representing the major risk factor for the development of insulin resistance (IR) and type 2 diabetes. We modeled these conditions in cultured 3T3-L1 adipocytes and studied their effect on insulin signaling, glucose uptake, and inflammatory response via activation of stress-dependent JNK1/2 kinases. Decreased insulin-induced phosphorylation of the insulin cascade components IRS, Akt, and AS160 was observed under all tested conditions (lipid overloading of cells by palmitate, acute inflammation induced by bacterial lipopolysaccharide, hypoxia induced by Co2+, and ER stress induced by brefeldin A). In all the cases, except the acute inflammation, glucose uptake by adipocytes was reduced, and the kinetics of JNK1/2 activation was bi-phasic exhibiting sustained activation for 24 h. By contrast, in acute inflammation, JNK1/2 phosphorylation increased transiently and returned to the basal level within 2–3 h of stimulation. These results suggest a critical role of sustained (latent) vs. transient (acute) inflammation in the induction of IR and impairment of glucose utilization by adipose tissue. The components of the inflammatory signaling can be promising targets in the development of new therapeutic approaches for preventing IR and type 2 diabetes.


insulin resistance type 2 diabetes inflammation glucose transport 



protein kinase B


Akt substrate of 160 kDa


brefeldin A


endoplasmic reticulum


free saturated fatty acid (palmitate in this work)


glucose transporter type 4


hypoxia-inducible factor 1α


insulin resistance


insulin receptor substrate


c-Jun N-terminal kinase


bacterial lipopolysaccharide


mammalian target of rapamycin complex 2


phosphoinositide 3-kinase


Tris buffer supplemented with 0.1% Tween 20


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Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • I. S. Stafeev
    • 1
    • 2
    Email author
  • S. S. Michurina
    • 1
    • 3
  • N. V. Podkuychenko
    • 1
    • 3
  • M. Y. Menshikov
    • 1
  • Ye. V. Parfyonova
    • 1
    • 2
  • A. V. Vorotnikov
    • 1
    • 4
    Email author
  1. 1.Institute of Experimental CardiologyNational Medical Research Center of CardiologyMoscowRussia
  2. 2.Faculty of Fundamental MedicineLomonosov Moscow State UniversityMoscowRussia
  3. 3.Faculty of BiologyLomonosov Moscow State UniversityMoscowRussia
  4. 4.Medical CenterLomonosov Moscow State UniversityMoscowRussia

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