Cited by 189Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismExercise and Physiological Responses

The DOI matches its Crossref record; 115 of the 120 references it cites were found in a registry or an index; 1 of the 222 sources its claims cite were checked for support.

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

Open access
de Oliveira dos Santos, Ana Rita, de Oliveira Zanuso, Bárbara, Miola, Vitor Fernando Bordin, Barbalho, Sandra Maria, Santos Bueno, Patrícia C., Flato, Uri Adrian Prync, Detregiachi, Claudia Rucco P., Buchaim, Daniela Vieira, Buchaim, Rogério Leone, Tofano, Ricardo José, Mendes, Claudemir Gregório, Tofano, Viviane Alessandra Capelluppi, dos Santos Haber, Jesselina F.·2021·International Journal of Molecular Sciences

Abstract

Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. This study aims to review the crosstalk between adipokines, myokines, and hepatokines. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This narrative review describes how adipokines, myokines, and hepatokines act through endocrine, paracrine, and autocrine crosstalk to influence insulin resistance, obesity, metabolic syndrome, and cardiovascular disease. It argues these organokines may serve as diagnostic/prognostic biomarkers and therapeutic targets, while calling for more in vivo and mechanistic studies.

Key findings

  • Adipose, skeletal muscle, and liver are the main endocrine organs producing adipokines, myokines, and hepatokines; these biomarkers can be harmful or beneficial and act together in a complex network affecting DM2, obesity, metabolic syndrome, and CVD.
  • Overweight individuals secrete more pro-inflammatory adipokines, leading to impaired immune response and greater susceptibility to inflammatory and infectious diseases; myostatin is elevated in pro-inflammatory environments alongside TNF-α, IL-1, resistin, and chemerin.
  • FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver; exercise shifts secretion toward anti-inflammatory organokines such as irisin, IL-6, IL-15, myonectin, adiponectin, and FGF21, which mitigate harmful effects of myostatin, TNF-α, resistin, chemerin, and fetuin-A.
  • The introduction cites an estimated 1.7 billion people vulnerable to health risks determined by body weight, 2.5 million deaths annually related to increased BMI expected to double by 2030, and CVDs responsible for approximately 17.9 million deaths per year, corresponding to 31% of total deaths worldwide.

Methods

  • Descriptive review using PUBMED-Medline, Embase, and Cochrane databases.
  • Mesh terms were adipokines, myokines, hepatokines, abdominal fat, insulin resistance, obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases.
  • Inclusion/exclusion was based on studies that included crosstalk among organokines, not just individual assessment of each one on insulin resistance, diabetes, obesity, metabolic syndrome, and cardiovascular complications.

Limitations

  • The paper states that in vivo experimental studies are further needed addressing crosstalk between adipokines, myokines, and hepatokines to support future clinical treatments, and that biochemical mechanisms of action of organokines are needed to guide future clinical trials.
  • Evident from the text: this is a descriptive/narrative review without a systematic protocol, risk-of-bias assessment, or quantitative synthesis; the search strategy and study selection are reported only briefly.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/ijms22052639

Cites

115 of 115 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Figures

Figure 1 Effects of leptin and adiponectin on the metabolism of the central nervous system, skeletal muscle, and liver. Black arrows represent the flow in metabolism; blue arrow represents increased action; red arrow represents decreased action; + represents activation; x represents inhibition. FFA: free fatty acid; NPY: neuropeptide Y; SkM: skeletal muscle; WAT: white adipose tissue.
Figure 1 Effects of leptin and adiponectin on the metabolism of the central nervous system, skeletal muscle, and liver. Black arrows represent the flow in metabolism; blue arrow represents increased action; red arrow represents decreased action; + represents activation; x represents inhibition. FFA: free fatty acid; NPY: neuropeptide Y; SkM: skeletal muscle; WAT: white adipose tissue.CC BY · PubMed Central
Figure 2 General actions of the main myokines in the metabolism. Physical exercise is the stimulus for the release of most myokines, while it inhibits myostatin release. The actions of these myokines are outlined as shown in the figure above. + represents activation; − represents inhibition; blue arrows reflect the actions of myokines stimulated by exercise; red arrows reflect the actions of myostatin; black arrows represent stimulation of physical exercises on skeletal muscle and the release of myokines. IL-6: interleukin-6; IL-15: interleukin-15; BDNF: brain-derived neurotrophic factor; FGF-21: fibroblast growth factor-21; SkM: Skeletal Muscle; WAT: White adipose tissue.
Figure 2 General actions of the main myokines in the metabolism. Physical exercise is the stimulus for the release of most myokines, while it inhibits myostatin release. The actions of these myokines are outlined as shown in the figure above. + represents activation; − represents inhibition; blue arrows reflect the actions of myokines stimulated by exercise; red arrows reflect the actions of myostatin; black arrows represent stimulation of physical exercises on skeletal muscle and the release of myokines. IL-6: interleukin-6; IL-15: interleukin-15; BDNF: brain-derived neurotrophic factor; FGF-21: fibroblast growth factor-21; SkM: Skeletal Muscle; WAT: White adipose tissue.CC BY · PubMed Central
Figure 3 Main functions of hepatokines and their respective activities. [↓] represents the decrease and [↑] represents the increase; black arrows represent the release of hepatokines and their actions on each specified target. FGF-21: fibroblast growth factor-21; ANGPTL4: Angiopoietin-Like 4; LECT2: Leukocyte cell-derived chemotaxin 2; SkM: Skeletal Muscle; WAT: white adipose tissue; CVD: Cardiovascular disease e IR: Insulin Resistance.
Figure 3 Main functions of hepatokines and their respective activities. [↓] represents the decrease and [↑] represents the increase; black arrows represent the release of hepatokines and their actions on each specified target. FGF-21: fibroblast growth factor-21; ANGPTL4: Angiopoietin-Like 4; LECT2: Leukocyte cell-derived chemotaxin 2; SkM: Skeletal Muscle; WAT: white adipose tissue; CVD: Cardiovascular disease e IR: Insulin Resistance.CC BY · PubMed Central
Figure 4 An overview of the crosstalk between adipokines, myokines and hepatokines. Adipokines are represented in brown, myokines in green and hepatokines in blue. The arrows that are indicating upward indicate an increase and downward decrease. (x) represents inhibition and (+) activation. Blue arrows are associated with benefits, while red arrows are associated with harm aspects. IL: interleukin; BDNF: brain-derived neurotrophic factor; FGF-21: fibroblast growth factor-21; SkM: skeletal muscle; WAT: white adipose tissue; CVD: cardiovascular disease; LECT2: leukocyte cell-derived chemotaxin 2; FFA: free fatty acid.
Figure 4 An overview of the crosstalk between adipokines, myokines and hepatokines. Adipokines are represented in brown, myokines in green and hepatokines in blue. The arrows that are indicating upward indicate an increase and downward decrease. (x) represents inhibition and (+) activation. Blue arrows are associated with benefits, while red arrows are associated with harm aspects. IL: interleukin; BDNF: brain-derived neurotrophic factor; FGF-21: fibroblast growth factor-21; SkM: skeletal muscle; WAT: white adipose tissue; CVD: cardiovascular disease; LECT2: leukocyte cell-derived chemotaxin 2; FFA: free fatty acid.CC BY · PubMed Central

Verification

Claims the paper makes

201 Not checked yet · 43 No basis given · 7 Own interpretation · 1 Couldn’t confirm · accuracy not yet measured

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Show all 121 claims

  • It may state two separate claims as one. 121
  • Probably not a substantial claim. 22
131 of 131
  • The paper relies on this without support.

    Adipose, skeletal muscle, and hepatic tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines.

    “Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines.”
  • The paper relies on this without support.

    These biomarkers can be harmful or beneficial and perform crosstalk through endocrine, paracrine, and autocrine pathways.

    “These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways.”
  • The paper relies on this without support.

    Many organokines are secreted by all three tissues.

    “Moreover, many organokines are secreted by all three tissues.”
  • The paper relies on this without support.

    No review has shown a comprehensive overview of crosstalk among these organokines with focus on insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease.

    “To the best of our knowledge, no review has shown a comprehensive overview of crosstalk or these organokines with focus on insulin resistance, diabetes, metabolic syndrome, and CVD.”
  • The paper relies on this without support.

    Overweight individuals secrete more pro-inflammatory adipokines than healthy-weight individuals, leading to impaired immune response and greater susceptibility to inflammatory and infectious diseases.

    “Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases.”
  • The paper relies on this without support.

    Myostatin is elevated in pro-inflammatory environments and co-occurs with pro-inflammatory organokines such as TNF-alpha, IL-1, resistin, and chemerin.

    “Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin.”
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Citations

Cites

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Research works printed but not linked: 2

  1. Sandhu, 2020, Cure of obesity in homeopathy: An approach to control a global epidemic, Tantian Univ. J. Homoeopath. Med. Sci., 1, 17
  2. Oliveira, 2019, Atualização da diretriz de prevenção cardiovascular da sociedade brasileira de cardiologia, Arq. Bras. Cardiol., 113, 787

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Metadata

Authors
de Oliveira dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., Mendes, C. G., Tofano, V. A. C., & dos Santos Haber, J. F.
Affiliations
  • Department of Biochemistry and Pharmacology, School of Medicine, University of Marília (UNIMAR), Avenida Higino Muzzi Filho 1001, Marília 17525-902, São Paulo, Brazil
  • Universidade de Marília (BR)
  • Postgraduate Program in Structural and Functional Interactions in Rehabilitation, University of Marilia (UNIMAR), Avenida Hygino Muzzy Filho 1001, Marília 17525-902, São Paulo, Brazil
  • Universidade de São Paulo (BR)
Corresponding author
Barbalho, Sandra Maria
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-03-05
Volume
22
Issue
5
Pages
2639
ISSN
1422-0067 (ISSN-L)
OpenAlex
W3133763745
Cited by
189
References
120
Citations by year
2026: 27 · 2025: 33 · 2024: 39 · 2023: 44 · 2022: 37 · 2021: 9
FWCI
4.94
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
  • Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
Keywords
adipokines, myokines, hepatokines, crosstalk, hormone signaling, paracrine signaling, autocrine signaling, type 2 diabetes, obesity, metabolic syndrome, cardiovascular disease, myostatin, FGF21, inflammatory cytokines, resistin, chemerin, TNF-α, interleukin-1, fatty acid beta-oxidation, lipogenesis, therapeutic target
MeSH terms
Animals, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Humans, Obesity, Cytokines, Metabolic Syndrome, Adipokines

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