Metabolic adaptation in obesity and type ii diabetes: myokines, adipokines and hepatokines
Open accessAbstract
Obesity and type II diabetes are characterized by insulin resistance in peripheral tissues. A high caloric intake combined with a sedentary lifestyle is the leading cause of these conditions. Whole-body insulin resistance and its improvement are the result of the combined actions of each insulin-sensitive organ. Among the fundamental molecular mechanisms by which each organ is able to communicate and engage in cross-talk are cytokines or peptides which stem from secretory organs. Recently, it was reported that several cytokines or peptides are secreted from muscle (myokines), adipose tissue (adipokines) and liver (hepatokines) in response to certain nutrition and/or physical activity conditions. Cytokines exert autocrine, paracrine or endocrine effects for the maintenance of energy homeostasis. The present review is focused on the relationship and cross-talk amongst muscle, adipose tissue and the liver as secretory organs in metabolic diseases.
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IL-6 secreted by adipocytes from obese patients negatively affects metabolic flexibility by decreasing insulin signaling and glucose uptake because of its proinflammatory properties.
“IL-6, is, however, also secreted by adipocytes from obese patients and negatively affects metabolic flexibility by decreasing insulin signaling and glucose uptake because of its proinflammatory properties (114, 123).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [114]
IL-6, when secreted by skeletal muscle, stimulates AMPK activity and in this way increases glucose uptake and β-oxidation in muscle and adipose tissue.
“IL-6, for instance, when secreted by skeletal muscle, stimulates AMPK activity and in this way increases glucose uptake and β-oxidation in muscle and adipose tissue (114).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [114]
Myokines play important roles in mediating the positive effects of exercise on whole-body metabolism.
“In particular, myokines play important roles in mediating the positive effects of exercise on whole-body metabolism [reviewed in Oh et al. (114)].”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [114]
SFRP5 is associated with comorbidities such as obesity, type 2 diabetes mellitus, insulin resistance, and atherosclerosis, inhibiting Wnt5a and non-canonical Wnt family and regulating expression of pro-inflammatory cytokines.
“SFRP5 is associated with comorbidities such as obesity, DM2, insulin resistance, and atherosclerosis, inhibiting the wingless-type family member 5a signaling (Wnt5a) and the non-canonical Wnt family and regulating the expression of pro-inflammatory cytokines [14,21].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
IL-6 is produced by macrophages and stimulated by activation of NF-kappaB and acts in inhibiting expression of IRS1 and GLUT4 in adipocytes.
“It is produced by macrophages and stimulated by the activation of the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and acts in inhibiting the expression of insulin receptor substrate 1 (IRS1) and glucose transporter type 4 (GLUT4) in adipocytes [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
Myokines are expressed mainly in physical activities or absence, allowing communication with other body tissues, showing actions that can be beneficial for most myokines or related to metabolic dysfunctions.
“These molecules are expressed mainly in physical activities or absence, allowing its communication with other body tissues, thereby showing actions that can be considered beneficial for most myokines or related to metabolic dysfunctions [8,14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
IL-15 helps in reduction of visceral adipose tissue without reducing subcutaneous fat, showing performance in muscle-fat crosstalk.
“Additionally, it helps in the reduction in visceral adipose tissue without reducing subcutaneous fat, showing performance in muscle-fat crosstalk [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
BDNF is related to glucose and lipid metabolism regulation and increased insulin sensitivity when released by muscle.
“Besides that, it is also related to glucose and lipid metabolism regulation and increased insulin sensitivity when released by muscle [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
Hepatokines have greater interference in fatty and striated skeletal muscle tissue, acting through crosstalk with cytokines released by these tissues.
“Even so, there is a greater interference of hepatokines in the fatty and striated skeletal muscle tissue, showing an endocrine-dependent relationship, therefore acting through crosstalk with the cytokines released by these respective tissues [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
SPARC is able to inhibit formation of adipose tissue, increase release of insulin, and promote erythropoiesis.
“It is also able to inhibit the formation of adipose tissue, increase the release of insulin and promote erythropoiesis [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
Chemerin hyperexpression is found in patients with NAFLD and nonalcoholic steatohepatitis (NASH).
“That is, chemerin hyperexpression is found in patients with NAFLD and nonalcoholic steatohepatitis [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
The Paigen diet is associated with NAFLD due to its high cholesterol content, which promotes liver chemerin expression.
“It has been found that the Paigen diet is associated with nonalcoholic fatty liver disease due to the high cholesterol content that promotes liver chemerin expression.”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
In obese and diabetic individuals, visceral fat is related to the expression of IL-6 and TNF-α produced by macrophages that prevent or attenuate insulin signaling in insulin-dependent tissues.
“In obese and diabetic individuals, visceral fat is related to the expression of IL-6 and TNF-α produced by macrophages that prevent or attenuate insulin signaling in insulin-dependent tissues.”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
IL-6 released during physical exercise can improve glucose and lipid metabolism.
“Despite this, IL-6 released during physical exercise can improve glucose and lipid metabolism, while plasma levels of TNF-α in exercise are reduced, although its expression in adipose tissue is not affected [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
Myostatin promotes the state of obesity, sarcopenia, and sarcopenic obesity.
“In parallel, myostatin promotes the state of obesity, sarcopenia, and sarcopenic obesity, which promotes the release of inflammatory adipokines and hepatokines while inhibiting the release of myokines and other anti-inflammatory and antioxidant organokines [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
Plasma levels of TNF-α in exercise are reduced, although its expression in adipose tissue is not affected.
“Despite this, IL-6 released during physical exercise can improve glucose and lipid metabolism, while plasma levels of TNF-α in exercise are reduced, although its expression in adipose tissue is not affected [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
Myostatin promotes the release of inflammatory adipokines and hepatokines while inhibiting the release of myokines and other anti-inflammatory and antioxidant organokines.
“In parallel, myostatin promotes the state of obesity, sarcopenia, and sarcopenic obesity, which promotes the release of inflammatory adipokines and hepatokines while inhibiting the release of myokines and other anti-inflammatory and antioxidant organokines [14].”
From Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions (2021) · cites this paper as [14]
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- Authors
- Oh, K.-J., Lee, D., Kim, W., Han, B., Lee, S., & Bae, K.-H.
- Affiliations
- Korea Research Institute of Bioscience and Biotechnology (KR)
- Corresponding author
- Lee, Sang
- Bae, Kwang-Hee
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2016-12-22
- Volume
- 18
- Issue
- 1
- Pages
- 8
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5297643
- OpenAlex
- W2563258252
- Cited by
- 210
- References
- 318
- Citations by year
- 2026: 7 · 2025: 18 · 2024: 16 · 2023: 20 · 2022: 23 · 2021: 33 · 2020: 28 · 2019: 24 · 2018: 30 · 2017: 11
- FWCI
- 2.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- 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)
- KRIBB Repository (submittedVersion)
- Funders
- National Research Foundation
- Korea Research Institute of Bioscience and Biotechnology (2012M3A9C7050101, 2015M3A9D7029882)
- National Research Foundation of Korea (2015M3A9D7029882, 2016R1C1B2010257, 2012M3A9C7050101)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- obesity, type 2 diabetes, insulin resistance, myokines, adipokines, hepatokines, cytokines, organ crosstalk, energy homeostasis, muscle, adipose tissue, liver, physical activity, energy intake
- MeSH terms
- Adaptation, Physiological, Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Humans, Liver, Muscles, Obesity, Adipokines
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