Conditioned medium obtained from in vitro differentiated adipocytes and resistin induce insulin resistance in human hepatocytes.
Adipocyte-derived factors might play a role in the development of hepatic insulin resistance. Resistin was identified as an adipokine linking obesity and insulin resistance. Resistin is secreted from adipocytes in rodents but in humans it was proposed to originate from macrophages and its impact for insulin resistance has remained elusive. To analyze the role of adipokines in general and resistin as a special adipokine, we cultured the human liver cell line HepG2 with adipocyte-conditioned medium (CM) containing various adipokines such as IL-6 and MCP-1, and resistin. CM and resistin both induce insulin resistance with a robust decrease in insulin-stimulated phosphorylation of Akt and GSK3. Insulin resistance could be prevented by co-treatment with troglitazone but not by co-stimulation with adiponectin. As human adipocytes do not secrete resistin, HepG2 cells were also treated with resistin added into CM. CM with resistin addition induced stronger insulin resistance than CM alone pointing to a specific role of resistin in the initiation of hepatic insulin resistance in humans.
Zhou
Lei
L
College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
Sell
Henrike
H
Eckardt
Kristin
K
Yang
Zaiqing
Z
Eckel
Jürgen
J
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D052242:Adiponectin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D017077:Culture Media, Conditioned; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D052243:Resistin / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
D052242:Adiponectin; D002839:Chromans; D017077:Culture Media, Conditioned; D052243:Resistin; D045162:Thiazolidinediones; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D000077288:Troglitazone