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. 2023 Feb 14;13(2):270. doi: 10.3390/metabo13020270

Table 1.

Main characteristics of novel organokines involved in the pathophysiology of obesity.

Organokine Putative Role in Obesity and Obesity-Related Disturbances Change Reference
Adipokines
Chemerin Mediation of obesity-associated low-grade inflammation;
Negative correlation with HDL-linked antioxidant paraoxonase-1 enzyme;
Strong correlation with the markers of dyslipidemia including lipoprotein subfractions;
Biomarker for obesity and insulin resistance;
Mechanistic influence on systolic blood pressure and hypertension.
[23,26,28,32]
PAI-1 Thrombotic effects and inflammation;
Biomarker for obesity, insulin resistance and T2DM;
Associations with the markers of atherogenic dyslipidemia (correlations with HDL subfractions and ApoAI; PAI-1 release stimulated by small-sized HDL in adipocytes; VLDL was capable of increasing the PAI-1 level in endothelial cells).
[33,35,36,41]
LCN-2 Biomarker for early renal injury;
Biomarker for insulin resistance;
Biomarker for hypertension;
High LCN-2 levels negatively affect muscle physiology.
[45,46,49,51]
PEDF Anti-angiogenic properties by direct effects on endothelial cells;
Role in lipid metabolism by the binding of adipose triglyceride lipase;
PEDF expression may be upregulated by a compensatory mechanism;
Biomarker for obesity, T2DM and MetS.
[55,56,59]
PGRN Growth factor in epithelial cells, fibroblasts and adipocytes;
Direct binding to TNFR inhibiting neutrophil activation;
Contradictory results in the progression of insulin resistance and inflammation;
PGRN expression may be upregulated by a compensatory mechanism;
Change of PGRN negatively correlated with the improvement of current perception threshold after 6-month alpha-lipoic treatment in T2DM patients with peripheral neuropathy.
↑↓ [60,61,63,65,68]
Vaspin Insulin-sensitizing and anti-inflammatory agent via a compensatory mechanism;
Involvement in hypertension;
Involvement in lipid metabolism;
Biomarker for obesity, T2DM and NAFLD.
↑↓ [71,72,75,76]
Omentin-1 Insulin sensitizing and anti-inflammatory agent;
Biomarker for MetS, hypertension, T2DM and diabetic complications;
Involvement in lipid metabolism
[77,79,80,81]
Metrnl Involvement in thermogenesis in brown/beige adipocytes;
Insulin sensitizing and anti-inflammatory effects;
Putative involvement in lipid metabolism.
↑↓ [85,86,89]
Hepatokines
Afamin Association with adiposity, markers of MetS and NAFLD;
Biomarker for the prevalence and incidence of T2DM and gestational diabetes;
Biomarker for unstable atherosclerotic plaque;
Involvement in HDL metabolism.
[96,97,99,101]
RBP4 Strong correlation with the markers of dyslipidemia including lipoprotein subfractions and ApoAI;
Association with adiposity, insulin resistance, MetS and T2DM.
↑↓ [103,105,106,109]
Fetuin-A Strong correlation with the markers of dyslipidemia including lipoprotein subfractions;
Putative association to HDL proteome;
Biomarker for obesity, MetS and T2DM;
Biomarker for subclinical atherosclerosis.
↑↓ [109,113,115,117,123]
FGF21 Insulin-sensitizing effects;
Regulator of thermogenesis and lipolysis in the brown adipose tissue;
FGF21 expression may be upregulated by a compensatory mechanism in obesity, T2DM and hypertension;
Short term moderately intensive physical activity improved FGF21 levels in T2DM patients with peripheral neuropathy.
↑↓ [127,128,133,134,135]
Gut hormones
Obestatin Anorexigenic and insulin-sensitizing effects;
Involvement in the pathophysiology of obesity, insulin resistance and T2DM;
Involvement in the regulation of lipid metabolism including VLDL and HDL subfractions, correlation with mean LDL size.
[139,142,145]
Ghrelin Orexigenic effects, stimulating gastric motility and hepatic glucose secretion and reducing insulin secretion;
Inducing growth hormone and glucocorticoid secretion;
Ghrelin expression is markedly decreased in obese individuals independently of gender.
[147,152,203]
Myokines
Irisin Insulin sensitizing hormone;
Involvement in lipid metabolism;
Biomarker for MetS, T2DM and cardiovascular diseases;
Increased levels after physical activity;
Decreased levels after weight loss due to bariatric surgery.
↑↓ [171,178,185,187]
Myostatin Negative regulator of skeletal muscle growth;
Levels are decreasing with age and exercise;
Related to systemic inflammation and sarcopenic obesity.
↑↓ [191,193,195]
Follistatin Promoting muscle mass and function;
Potential therapeutic use for the treatment of muscle wasting in cachexic conditions;
Involvement in beige and brown adipose tissue differentiation.
↑↓ [197,202]

Abbreviations: ↑ increased; ↓ decreased; ApoAI, apolipoprotein AI; FGF21, Fibroblast growth factor 21; HDL, high-density lipoprotein; LCN-2, lipocalin-2; LDL, low-density lipoprotein; Metrnl, Meteorin-like; MetS, metabolic syndrome; NAFLD, non-alcoholic fatty liver disease; PAI-1, plasminogen-activator inhibitor-1; PEDF, pigment epithelium derived factor; PGRN, progranulin; RBP4, Retinol-binding protein 4; TNFR, tumor necrosis factor alpha receptor; T2DM, type 2 diabetes mellitus; VLDL, very low-density lipoprotein.