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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
Article
  • 3 Downloads

Abstract

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.

Keywords

insulin resistance type 2 diabetes inflammation glucose transport 

Abbreviations

Akt

protein kinase B

AS160

Akt substrate of 160 kDa

BrA

brefeldin A

ER

endoplasmic reticulum

FFA

free saturated fatty acid (palmitate in this work)

GLUT4

glucose transporter type 4

HIF-1α

hypoxia-inducible factor 1α

IR

insulin resistance

IRS

insulin receptor substrate

JNK

c-Jun N-terminal kinase

LPS

bacterial lipopolysaccharide

mTORC2

mammalian target of rapamycin complex 2

PI3K

phosphoinositide 3-kinase

TBST

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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