The Roles of Adipokines, Proinflammatory Cytokines, and Adipose Tissue Macrophages in Obesity-Associated Insulin Resistance in Modest Obesity and Early Metabolic Dysfunction
Open accessAbstract
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.
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Many proinflammatory cytokines, including IFN-γ, TNF-α, MCP-1, IL-1β, IL-5, IL-6, IL-10, IL-12, IL-13, and IL-18, are increased in obese patients.
“In accordance with this theory, many proinflammatory cytokines have been found to be increased in obese patients, including IFN-γ, TNF-α, MCP-1, IL-1β, IL-5, IL-6, IL-10, IL-12, IL-13, and IL-18 [235,236].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [236]
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References 55 · Cited by 306
- Authors
- Kang, Y. E., Kim, J. M., Joung, K. H., Lee, J. H., You, B. R., Choi, M. J., Ryu, M. J., Ko, Y. B., Lee, M. A., Lee, J., Ku, B. J., Shong, M., Lee, K. H., & Kim, H. J.
- Affiliations
- Chungnam National University Hospital (KR)
- The Catholic University of Korea Daejeon St. Mary's Hospital (KR)
- Chungnam National University (KR)
- Corresponding author
- Kim, Hyun Jin
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2016-04-21
- Volume
- 11
- Issue
- 4
- Pages
- e0154003
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4839620
- OpenAlex
- W2336756101
- Cited by
- 306
- References
- 55
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 19 · 2023: 19 · 2022: 36 · 2021: 38 · 2020: 51 · 2019: 41 · 2018: 36 · 2017: 28 · 2016: 7
- FWCI
- 34.95
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Research Foundation of Korea (2014R1A1A1006176)
- Korea Otsuka Pharmaceuticals
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- obesity, insulin resistance, adipokines, inflammatory cytokines, adipose tissue macrophages, visceral adipose tissue, MCP-1, TNF-α, resistin, leptin, adiponectin, macrophage phenotype, HOMA-IR, body mass index
- MeSH terms
- Adipose Tissue, Adult, Female, Humans, Insulin Resistance, Macrophages, Middle Aged, Obesity, Case-Control Studies, Cytokines, Inflammation Mediators, Adipokines
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