Cytokines and inflammation in adipogenesis: an updated review

doi:10.1007/s11684-018-0625-0

Front. Med.

2019, Vol. 13

Issue (3) : 314-329 https://doi.org/10.1007/s11684-018-0625-0

REVIEW

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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Abstract

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 Author(s): 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.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0625-0
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I3/314

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	↓	[⁶–⁹]
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	↓	[¹⁶–¹⁸]
	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	↓	[²⁶–²⁸]
	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]
Interferons	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.

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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