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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (3) : 314-329
Cytokines and inflammation in adipogenesis: an updated review
Ning Jiang, Yao Li, Ting Shu, Jing Wang()
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Pathophysiology, Peking Union Medical College, Beijing 100730, China
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The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNFα and IL-1β) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy, ectopic lipid accumulation, and insulin resistance. Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome. This review focuses on the cytokines currently known to regulate adipogenesis under physiological and pathophysiological circumstances. Recent studies on how inhibited adipogenesis leads to metabolic disorders were summarized. Although the interplay of cytokines and lipid metabolism is yet incompletely understood, cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

Keywords cytokines      inflammation      adipogenesis      type 2 diabetes mellitus      metabolic disorder     
Corresponding Authors: Jing Wang   
Just Accepted Date: 28 May 2018   Online First Date: 01 August 2018    Issue Date: 05 June 2019
 Cite this article:   
Ning Jiang,Yao Li,Ting Shu, et al. Cytokines and inflammation in adipogenesis: an updated review[J]. Front. Med., 2019, 13(3): 314-329.
Family of cytokines Symbol Cytokine name Primary property Receptor Major sources of secretion in adipose tissue Model Effect on adipogenesis References
TNFa Tumor necrosis factor a Pro-inflammatory TNFR-1, TNFR-2 Cells of the monocyte/macrophage lineage, including adipose tissue macrophages Human abdominal subcutaneous preadipocytes, 3T3-L1 cells, 3T3-F442A cells [69]
IL-1 family IL-1b Interleukin-1b Pro-inflammatory IL-1R1, IL-1R2 Cells of the monocyte/macrophage lineage Human abdominal subcutaneous preadipocytes [10]
IL-18 Interleukin-18 Pro-inflammatory IL-18R Macrophages, DC, epithelial cells, endothelial cells Unknown
IL-33 Interleukin-33 Pro-inflammatory ST2 Necrotic cells, cells under stress Wistar rat (pre)adipocytes, 3T3-L1 cells, C57BL/6 mouse (pre)adipocytes, BALB/c mouse (pre)adipocytes [11,12]
IL-1F6 Interleukin-1F6 Pro-inflammatory IL-1Rrp2 Stromal vascular fraction Human subcutaneous abdominal (pre)adipocytes, human SGBS cells [13]
IL-1Ra Interleukin-1Ra Anti-inflammatory IL-1R1 Stromal vascular fraction C57BL/6J mouse epididymal (pre)adipocytes [14]
IL-37 Interleukin Anti-inflammatory IL-18Ra Mature adipocytes and vascular stromal cells Human SGBS cells [15]
Gp130 cytokines IL-6 Interleukin-6 Pro-inflammatory IL-6Ra Adipose tissue macrophages Human subcutaneous (pre)adipocytes, 3T3-L1 cells, 3T3-F442A cells [1618]
IL-11 Interleukin-11 Pro-inflammatory IL-11R Stromal vascular cells Human long term marrow cultures, 3T3-L1 cells [19,20]
OSM Oncostatin M Pro-inflammatory Type 1 OSM receptor, type 2 OSM receptor 3T3-L1 cells, mouse embryonic fibroblasts [21]
NP Neuropoietin ? CNTFRa 3T3-L1 cells [22]
IL-4 Interleukin-4 Pro-inflammatory/ anti-inflammatory IL-4R Lymphocytes, basophils and mast cells 3T3-L1 cells [23]
IL-10 Interleukin-10 Anti-inflammatory IL-10R T helper cells, monocytes/macrophages, dendritic cells, B cells Unknown
IL-15 Interleukin-15 Pro-inflammatory IL-15Ra Adipocytes and stromal vascular cells 3T3-L1 cells [24]
IL-7 Interleukin-7 Pro-inflammatory IL-7R Stromal vascular cells Mouse epididymal (pre)adipocytes [25]
IL-17 Interleukin-17 Pro-inflammatory IL-17R T helper cells 3T3-L1 cells [2628]
IL-34 Interleukin-34 Pro-inflammatory CSF-1 receptor Adipocytes and stromal vascular cells Human subcutaneous preadipocytes [29]
Interferons IFN-a Interferon-a Pro-inflammatory Type I interferon?receptors Fibroblasts?and?monocytes 3T3-L1 cells; human primary (pre)adipocytes [30]
IFN-g Interferon-g Pro-inflammatory Type II interferon?receptors T helper cells Mouse mesenchymal stem cells, 3T3-L1 cells, primary mouse (pre)adipocytes, human visceral (pre)adipocytes ↓↑ [31,32]
MCP-1 (CCL-2) Monocyte chemoattractant protein-1 (chemokine (C-C motif) ligand 2) Pro-inflammatory CCR2 Adipocytes, macrophages and endothelial cells 3T3-L1 cells, murine tissue engineering model [33,34]
Tab.1  Cytokines that regulate adipogenesis
Fig.1  TNFa signaling regulates adipogenesis. Signaling of TNFa through TNFR leads to activation of multiple pathways including NF-kB, p38, JNK, and ERK1/2. Wnt/b-catenin/TCF dependent pathway and numerous microRNAs are also activated. The activation of these pathways results in adipogenesis inhibition and suppression of PPARg and C/EBPa expression and activity, which are important transcriptional regulators of adipogenesis.
Name Effect on adipogenesis Targets The impact of TNFa on microRNAs References
miR-221 PPARg [35]
miR-155 C/EBPb, CREB [36]
miR-27 C/EBPb, CREB [36]
miR-103 [37]
miR-143 [37]
has-miR-26b PTEN [37]
miR-378 [37]
Tab.2  Regulatory effect of microRNAs on adipogenesis
Fig.2  IL-1b signaling affects adipogenesis. IL-1b is mainly produced by macrophages in adipose tissue, with small amounts being synthesized by adipocytes. It binds to type 1 IL-1 receptor to activate intracellular signaling including NF-kB pathway, which inhibits adipogenesis.
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