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. 2022 Mar 29;16:798995. doi: 10.3389/fnint.2022.798995

TABLE 1.

Main cytokines and their effects in obesity.

Cytokines Cytokine source Levels in obesity Cytokine mechanisms in obesity References
IL1β • Subcutaneous adipose tissue
• Visceral adipose tissue
↑ adipose tissue
↑ serum
• Induces Pre-adipocyte differentiation.
• Reduction of insulin-induced glucose transport.
• Inhibition of glucose uptake by adipocytes via ERK signaling.
• Acts synergistically with TNFα and IL6, altering the lipase activity, leading to lipid accumulation in the liver and muscle.
• Contribution to hepatic lipogenesis, triglyceride accumulation, and development of hepatic steatosis.
• IL6 production.
• T cell and macrophage activation.
Jager et al., 2007; Um et al., 2011; McArdle et al., 2013; Negrin et al., 2014; Wang et al., 2021
IL2 • Visceral adipose tissue
• CD4 + and CD8 + T cells
• Dendritic cells
• Macrophages
↑ adipose tissue
↑ serum
• T cell activation.
• Induction of inflammatory molecules like IL8, IL12A, CCL5, CCL19, CCR2, and CCR5.
• Contribution to increased insulin resistance secondary to TLR2, TLR4, and TLR10 interaction.
Liu and Nikolajczyk, 2019; Kochumon et al., 2020
IL4 • TH2 cells
• Visceral adipose tissue
• M2 macrophages
↓adipose tissue
↓serum
• Inhibits lipid deposits.
• Inhibits adipogenesis through the expression of peroxisome proliferator-activated receptor γ (PPARγ).
• Promotes lipolysis due to binding to hormone-sensitive lipase (HSL).
Tsao et al., 2014; Lu et al., 2015; Shiau et al., 2019
IL6 • Subcutaneous adipose tissue
• Visceral adipose tissue
• Monocytes
• M1 macrophages
↑ adipose tissue
↓ hypothalamus
• Promotes energy consumption by stimulating the hypothalamus.
• Correlation with high TNFα levels and insulin resistance.
• Chemotaxis and monocyte infiltration in adipose tissue by the expression of CD11b and CD163.
Sindhu et al., 2015; Kern et al., 2019; El-Mikkawy et al., 2020; Wang et al., 2021
IL10 • TH2 cells
• Regulatory T cells
• B cells
• M2 macrophages
↓ adipose tissue
↓ serum
• Inhibition of pro-inflammatory cytokine synthesis by suppressing NF-kB in macrophages.
• Association with hypertriglyceridemia by the affection of the JAK-STAT 3 signaling pathway.
Azizian et al., 2016; Kondo et al., 2018; Liu et al., 2018
IL13 • TH2 cells ↑ serum • Polarization of macrophages into an M2 profile through the IL-13Rα1/IL-4R receptor.
• Decrease insulin resistance.
• Involved in increasing inflammation via the NLRP3 inflammasome.
• Increases fatty acid oxidation in muscle.
Duffen et al., 2018; Martínez-Reyes et al., 2018; Knudsen et al., 2020
IL17 • Th17 cells in visceral adipose tissue
• M1 macrophages
• Neutrophils
↑ adipose tissue • Inhibition of adipocyte differentiation.
• Increase of inflammatory molecules like COX2 and PEG2.
• Induction of IL6 synthesis by adipocytes.
• CDK5-dependent phosphorylation of PPARγ in adipocytes, favoring gene expression related to diabetes.
Ahmed and Gaffen, 2010; Liu and Nikolajczyk, 2019; Teijeiro et al., 2021
IFNγ • TH1 cells ↑ adipose tissue
↑ serum
• Macrophage regulation switching to the M1 profile.
• Increase of insulin resistance.
• Increase of adipocyte cell size.
Wada et al., 2011; O’Rourke et al., 2012; Wang et al., 2014; Surendar et al., 2019
MCP1 (CCL2) • M1 macrophages ↑ adipose tissue
↑ serum
• Participation in adipogenesis promoting adipocyte growth.
• Facilitation of insulin resistance and glucose intolerance.
• Recruitment of immune cells.
Rocha et al., 2008; Cranford et al., 2016
TGFβ • Regulatory T cells
• M2 macrophages
• Platelets
↑ serum • Increase insulin resistance through TGFβ/Smad3 signaling via the repression of the insulin promoter and suppression of insulin level and secretion.
• Inhibition of adipocyte differentiation.
• Correlation with high levels of serum glucose.
Yadav et al., 2011; Zamani and Brown, 2011; Hong et al., 2016; Lee, 2018
TNFα • TH1 cells
• Subcutaneous adipose tissue
• Visceral adipose tissue
• M1 macrophages
↑ adipose tissue
↑ serum
• Inhibition of GLUT4 membrane translocation.
• Induction of the serine phosphorylation of insulin substrate-1, leading to insulin resistance.
• Suppression of the lipoprotein lipase activity.
• Inhibitor of adipocyte differentiation.
• Suppression of genes involved in uptake and storage of non-esterified fatty acids and glucose.
Bennet et al., 2006; Tzanavari et al., 2010; Kern et al., 2019; Liu and Nikolajczyk, 2019; Alzamil, 2020; Wang et al., 2021