The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction.
The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance have been explored in both animal and human studies. However, our current understanding of obesity-associated insulin resistance relies on studies of artificial metabolic extremes. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in human patients with modest obesity and early metabolic dysfunction. We obtained omental adipose tissue and fasting blood samples from 51 females undergoing gynecologic surgery. We investigated serum concentrations of proinflammatory cytokines and adipokines as well as the mRNA expression of proinflammatory and macrophage phenotype markers in visceral adipose tissue using ELISA and quantitative RT-PCR. We measured adipose tissue inflammation and macrophage infiltration using immunohistochemical analysis. Serum levels of adiponectin and leptin were significantly correlated with HOMA-IR and body mass index. The levels of expression of MCP-1 and TNF-α in visceral adipose tissue were also higher in the obese group (body mass index ≥ 25). The expression of mRNA MCP-1 in visceral adipose tissue was positively correlated with body mass index (r = 0.428, p = 0.037) but not with HOMA-IR, whereas TNF-α in visceral adipose tissue was correlated with HOMA-IR (r = 0.462, p = 0.035) but not with body mass index. There was no obvious change in macrophage phenotype or macrophage infiltration in patients with modest obesity or early metabolic dysfunction. Expression of mRNA CD163/CD68 was significantly related to mitochondrial-associated genes and serum inflammatory cytokine levels of resistin and leptin. These results suggest that changes in the production of inflammatory biomolecules precede increased immune cell infiltration and induction of a macrophage phenotype switch in visceral adipose tissue. Furthermore, serum resistin and leptin have specific roles in the regulation of adipose tissue macrophages in patients with modest obesity or early metabolic dysfunction.
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Yea Eun
0000-0002-2012-3716
YE
Kang
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Ji Min
JM
Kim
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Kyong Hye
KH
Joung
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Ju Hee
JH
Lee
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Bo Ram
BR
You
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Min Jeong
MJ
Choi
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Min Jeong
MJ
Ryu
Department of Obstetrics and Gynecology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Young Bok
YB
Ko
Department of Obstetrics and Gynecology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Min A
MA
Lee
Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
Junguee
J
Lee
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.|Department of internal medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Bon Jeong
BJ
Ku
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.|Department of internal medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Minho
M
Shong
Department of Obstetrics and Gynecology, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Ki Hwan
KH
Lee
Department of Internal medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Hyun Jin
HJ
Kim
D054392:Adipokines / Q000502:physiology*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000502:physiology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*
D054392:Adipokines; D016207:Cytokines; D018836:Inflammation Mediators