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Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway
Abstract
Background/objectives It has been reported that irisin regulated exercise-mediated adipocyte browning; however, the systematical effects of irisin on the metabolism of glucose and lipid in diabetes are largely unknown. In the present study, we investigated the role and underlying mechanism of irisin in glucose utilization and lipid metabolism in diabetic mice.Methods A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated.Results Irisin improved glucose tolerance and glucose uptake as evidenced by increased (18)F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-β phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid β-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes.Conclusions Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.
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“In SkM, after physical activity, irisin induced downstream activation of glucose and FFA uptake and oxidation [62].”
In the citing paper
“Exercise-inducible myokines, such as irisin [62,63], IL-6 [76,77], IL-15 [91,126], BAIBA [111], and METRNL [100], as well as the osteokine OCN [71] have been shown to directly stimulate oxidative metabolism in autocrine and endocrine ways, respectively (1).”
In the citing paper
“Other studies have reported effects of irisin on body fat reduction through other mechanisms, such as improved glucose tolerance and lipid oxidation via phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA-carboxylase [52, 53].”
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“Among other important functions are glucose/ lipid metabolism (Luo et al. 2020; Vaughan et al. 2014; Xin et al. 2016), neuronal development (Hashemi et al. 2013; Wrann et al. 2013), cardiovascular improvements (Grzeszc-zuk et al. 2024), and reproduction (Khan et al., 2024; Wahab et al. 2019; 2020).”
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Syringaresinol activates the skeletal muscle SIRT1–FNDC5/irisin axis to enhance weight management
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“In addition, Irisin improves glucose tolerance (Xin et al. 2016), enhances insulin sensitivity (Song et al. 2021 ), reduces inflammation (Slate-Romano et al. 2022), and confers protection against obesity-associated metabolic dysfunctions (Zhang et al. 2023).”
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Metadata
- Authors
- Xin, C., Liu, J., Zhang, J., Zhu, D., Wang, H., Xiong, L., Lee, Y., Ye, J., Lian, K., Xu, C., Zhang, L., Wang, Q., Liu, Y., & Tao, L.
- Affiliations
- Second Artillery General Hospital of Chinese People's Liberation Army (CN)
- Xijing Hospital (CN)
- Corresponding author
- Liu, Y
- Tao, L
- Venue
- International Journal of Obesity
- Published
- 2015-09-25
- Volume
- 40
- Issue
- 3
- Pages
- 443-451
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W1923336662
- Cited by
- 248
- References
- 44
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 24 · 2023: 26 · 2022: 28 · 2021: 32 · 2020: 29 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 12 · 2015: 1
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- irisin, type 2 diabetes, AMPK signaling, fatty acid oxidation, glucose utilization, glucose uptake, GLUT4 translocation, skeletal muscle, gluconeogenesis, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, hepatic glucose metabolism, lipid metabolism, ACACB, UCP1, high-fat diet, glucose tolerance
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Experimental, Disease Models, Animal, Fatty Acids, Fibronectins, Glucose, Male, Mice, Inbred C57BL, Oxidation-Reduction, Phosphorylation, Signal Transduction, Muscle, Skeletal, Lipid Metabolism, Glucose Transporter Type 4, Mice, AMP-Activated Protein Kinases
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