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

Crucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity

Hajnalka Lőrincz  1 , Sándor Somodi  2   3 , Balázs Ratku  2   3   4 , Mariann Harangi  1   3 , György Paragh  1
Affiliations
Review

Crucial Regulatory Role of Organokines in Relation to Metabolic Changes in Non-Diabetic Obesity

Hajnalka Lőrincz et al. Metabolites. .

Abstract

Obesity is characterized by an excessive accumulation of fat leading to a plethora of medical complications, including coronary artery disease, hypertension, type 2 diabetes mellitus or impaired glucose tolerance and dyslipidemia. Formerly, several physiological roles of organokines, including adipokines, hepatokines, myokines and gut hormones have been described in obesity, especially in the regulation of glucose and lipid metabolism, insulin sensitivity, oxidative stress, and low-grade inflammation. The canonical effect of these biologically active peptides and proteins may serve as an intermediate regulatory level that connects the central nervous system and the endocrine, autocrine, and paracrine actions of organs responsible for metabolic and inflammatory processes. Better understanding of the function of this delicately tuned network may provide an explanation for the wide range of obesity phenotypes with remarkable inter-individual differences regarding comorbidities and therapeutic responses. The aim of this review is to demonstrate the role of organokines in the lipid and glucose metabolism focusing on the obese non-diabetic subgroup. We also discuss the latest findings about sarcopenic obesity, which has recently become one of the most relevant metabolic disturbances in the aging population.

Keywords: adipokine; cardiovascular risk; hepatokine; insulin resistance; metabolically healthy obesity; myokine; non-diabetic obesity; prediabetes; sarcopenic obesity.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relationship between different type of organokines in non-diabetic obese (NDO) subjects. Genetic and environmental factors, aging population, stress, sedentary lifestyle, impaired microbiome, overnutrition are associated with growing incidence of obesity. Visceral adipose tissue, liver, gastrointestinal tract and skeletal muscle are potent endocrine organs which regulate energy and metabolic homeostasis via the secretion of adipokines, hepatokines, gut hormones and myokines. These organokines can interact with each other and communicate through various endocrine, paracrine and autocrine pathways. The concentrations of organokines change during the pathological conditions leading to prediabetic and then diabetic status in morbid obesity. The impaired organokine secretion may lead to further unfavourable obesity-associated disorders including sarcopenic obesity, atherosclerosis, CVD and NAFLD. Abbreviations: ↑, increased; ↓, decreased; CVD, cardiovascular disease; FGF21, fibroblast growth factor 21; LCN-2, lipocalin-2; Metrln, meteorin-like, NAFLD; non-alcoholic fatty liver disease; NDO, non-diabetic obese; PAI-1, plasminogen activator inhibitor-1; PEDF, pigment epithelium derived factor, PGRN, progranulin; RBP4, retinol binding protein 4; T2DM, type 2 diabetes mellitus. The graphical components of this figure are available on the website of iStock by Getty Images, Calgary, Alberta, Canada.
Figure 2
Figure 2
Range of obesity phenotypes with different cardiometabolic status. The graphical components of this figure are available on iStock by Getty Images, Calgary, Alberta, Canada.
Figure 3
Figure 3
Putative role of chemerin in metabolic processes. The graphical components of this figure are available on iStock by Getty Images, Calgary, Alberta, Canada.
Figure 4
Figure 4
Pathophysiological role of afamin. The graphical components of this figure are available on iStock by Getty Images, Calgary, Alberta, Canada.
Figure 5
Figure 5
Involvement of organokines in the regulation of neuroendocrine axis. The graphical components of this figure are available on iStock by Getty Images, Calgary, Alberta, Canada.
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