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