Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway

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

doi:10.1038/ijo.2015.199

Cited by 249Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismMetabolism, Diabetes, and Cancer

Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway

Xin, C, Liu, J, Zhang, J, Zhu, D, Wang, H, Xiong, L, Lee, Y, Ye, J +6 more·2016·International Journal of Obesity

DOI 10.1038/ijo.2015.199

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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 skeletal muscle after physical activity, irisin induces downstream activation of glucose and free fatty acid uptake and oxidation.
“In SkM, after physical activity, irisin induced downstream activation of glucose and FFA uptake and oxidation [62].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [62]
Exercise-inducible myokines irisin, IL-6, IL-15, BAIBA, and METRNL, as well as osteokine OCN, directly stimulate oxidative metabolism in autocrine and endocrine ways.
“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).”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [62]
Other studies have reported effects of irisin on body fat reduction through mechanisms other than UCP-1, such as improved glucose tolerance and lipid oxidation via phosphorylation of AMPK and acetyl-CoA-carboxylase.
“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].”
From β-hydroxy-β -methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue (2021) · cites this paper as [52]

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Mahgoub, M., D’Souza, C. M., Darmaki, R. S. A., Baniyas, M. M. Y. H., & Adeghate, E. A. (2018) · Peptides · doi:10.1016/j.peptides.2018.03.018 · Cited by 109 · see citing works
Irisin ameliorates depressive-like behaviors in rats by regulating energy metabolism
Wang, S., & Pan, J. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.04.047 · Cited by 107 · see citing works
Irisin, a fascinating field in our times
Bao, J., She, Q.-Y., Hu, P., Jia, N., & Li, A. (2022) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2022.06.003 · Cited by 102 · see citing works
FNDC5/Irisin attenuates diabetic cardiomyopathy in a type 2 diabetes mouse model by activation of integrin αV/β5-AKT signaling and reduction of oxidative/nitrosative stress
Lin, C., Guo, Y., Xia, Y., Li, C., Xu, X., Qi, T., Zhang, F., Fan, M., Hu, G., Zhao, H., et al. (2021) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2021.06.013 · Cited by 100 · see citing works
Research progress in the role and mechanism of Leucine in regulating animal growth and development
Rehman, S. U., Ali, R., Zhang, H., Zafar, M. H., & Wang, M. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1252089 · Cited by 97 · see citing works
“Coenzyme inactivity Carboxylase activity activates AMPK, which boosts fat oxidation, lowers glucose generation, affects cholesterol and total triglyceride formation, disrupts mTOR signaling, and inhibits lipogenesis (Xin et al., 2016).”
Background
Effects of irisin on the dysfunction of blood–brain barrier in rats after focal cerebral ischemia/reperfusion
Guo, P., Jin, Z. Y., Wu, H., Li, X., Ke, J., Zhang, Z., & Zhao, Q. (2019) · Brain and Behavior · doi:10.1002/brb3.1425 · Cited by 92 · see citing works
Insulin resistance and adipose tissue interactions as the cornerstone of metabolic (dysfunction)-associated fatty liver disease pathogenesis
Pal, S. C., & Méndez‐Sánchez, N. (2023) · World Journal of Gastroenterology · doi:10.3748/wjg.v29.i25.3999 · Cited by 91 · see citing works
Irisin-mediated protective effect on LPS-induced acute lung injury via suppressing inflammation and apoptosis of alveolar epithelial cells
Shao, L., Meng, D., Yang, F., Song, H., & Tang, D. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.04.020 · Cited by 90 · see citing works
The Role of Irisin in Alzheimer’s Disease
Kim, O. Y., & Song, J. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7110407 · Cited by 90 · see citing works
“Irisin decreases the expression of G6Pase and PEPCK, both of which are critical for gluconeogenesis, in the liver [66].”
Background
Exercise hormone irisin mitigates endothelial barrier dysfunction and microvascular leakage–related diseases
Bi, J., Zhang, J., Ren, Y., Du, Z., Zhang, Y., Liu, C., Wang, Y., Zhang, L., Shi, Z., Wu, Z., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.136277 · Cited by 88 · see citing works
“Interestingly, several studies have reported that the regulatory role of irisin in energy metabolism is associated with activation of AMPK (15, 29).”
Background
Sarcopenic obesity: Myokines as potential diagnostic biomarkers and therapeutic targets?
Guo, A., Li, K., & Xiao, Q. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111022 · Cited by 83 · see citing works
The Potential Role of Contraction-Induced Myokines in the Regulation of Metabolic Function for the Prevention and Treatment of Type 2 Diabetes
Carson, B. P. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00097 · Cited by 83 · see citing works
“Irisin treatment of myocytes also elevated FA oxidation suggesting a protective effect against progression of T2D (75).”
Background
Irisin ameliorates hepatic glucose/lipid metabolism and enhances cell survival in insulin-resistant human HepG2 cells through adenosine monophosphate-activated protein kinase signaling
So, W. Y., & Leung, P. S. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.07.022 · Cited by 83 · see citing works
High irisin levels are associated with better glycemic control and bone health in children with Type 1 diabetes
Faienza, M. F., Brunetti, G., Sanesi, L., Colaianni, G., Celi, M., Piacente, L., D’Amato, G., Schipani, E., Colucci, S. C., & Grano, M. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.03.046 · Cited by 82 · see citing works
Myricanol modulates skeletal muscle–adipose tissue crosstalk to alleviate high‐fat diet‐induced obesity and insulin resistance
Shen, S., Liao, Q., Zhang, T., Pan, R., & Lin, L. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14802 · Cited by 86 · see citing works
“Treatment with irisin increases mitochondrial oxidative metabolism, mitochondrial uncoupling, and fatty acid oxidation in skeletal muscle (Xin et al., 2016).”
Background
A polymorphism in the Irisin-encoding gene (FNDC5) associates with hepatic steatosis by differential miRNA binding to the 3′UTR
Metwally, M., Bayoumi, A., Romero‐Gómez, M., Thabet, K., John, M., Adams, L. A., Huo, X., Aller, R., García‐Monzón, C., Arias, M., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.10.021 · Cited by 81 · see citing works
“This data is supported by animal studies that FNDC5 improves hepatic steatosis, protects mice against genetic- and diet-induced obesity, and improves hepatic and peripheral insulin resistance via regulating AMPK signaling in myocytes and hepatocytes [34, 36-38].”
Result
Decreased level of irisin, a skeletal muscle cell-derived myokine, is associated with post-stroke depression in the ischemic stroke population
Tu, W., Qiu, H., Liu, Q., Li, X., Zhao, J.-Z., & Zeng, X. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1177-6 · Cited by 79 · see citing works
“Accumulating evidence has demonstrated that irisin contributes to the regulation of glucose and lipid metabolism in the skeletal muscle and adipose tissue [7, 8].”
Background
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79 · see citing works
The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients
Chang, C. L., Huang, S. Y., Hsu, Y. C., Chin, T. H., & Soong, Y. K. (2019) · Scientific Reports · doi:10.1038/s41598-019-42061-9 · Cited by 76 · see citing works
The effects of both age and sex on irisin levels in paired plasma and cerebrospinal fluid in healthy humans
Ruan, Q., Huang, Y., Yang, L., Ruan, J., Gu, W., Zhang, X., Zhang, Y., Zhang, W., & Yu, Z. (2019) · Peptides · doi:10.1016/j.peptides.2019.01.004 · Cited by 76 · see citing works
Plasma Irisin Modestly Increases during Moderate and High-Intensity Afternoon Exercise in Obese Females
Winn, N. C., Grunewald, Z. I., Liu, Y., Heden, T. D., Nyhoff, L. M., & Kanaley, J. A. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170690 · Cited by 69 · see citing works
Decreased Concentration of Irisin Is Associated with Poor Functional Outcome in Ischemic Stroke
Tu, W., Qiu, H., Cao, J., Liu, Q., Zeng, X., & Zhao, J.-Z. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0651-2 · Cited by 67 · see citing works
Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions
Zhang, D., Xie, T., & Leung, P. S. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000495395 · Cited by 65 · see citing works
Adipose–Muscle Crosstalk in Age-Related Metabolic Disorders: The Emerging Roles of Adipo-Myokines
Fang, P., She, Y., Yu, M., Min, W., Shang, W., & Zhang, Z. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101829 · Cited by 62 · see citing works
The Role of Irisin in Cancer Disease
Pinkowska, A., Podhorska‐Okołów, M., Dzięgiel, P., & Nowińska, K. (2021) · Cells · doi:10.3390/cells10061479 · Cited by 61 · see citing works
“Ir enhanced glucose utilization by increasing 5’AMP-activated protein kinase (AMPK) phosphorylation in myocytes and hepatocytes of diabetic mice in in vitro and in vivo studies [54].”
Background
Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions
Senesi, P., Luzi, L., & Terruzzi, I. M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218372 · Cited by 61 · see citing works
“Further, irisin plays an important role in hepatic metabolism reducing lipogenesis and gluconeogenesis and increasing lipid oxidation and glycolysis [137,138].”
Background
Irisin Attenuates Myocardial Ischemia/Reperfusion Injury and Improves Mitochondrial Function Through AMPK Pathway in Diabetic Mice
Xin, C., Zhang, Z., Gao, G., Ding, L., Yang, C., Wang, C.-Z., Liu, Y.-J., Guo, Y.-F., Yang, X.-Q., Zhang, L.-J., et al. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.565160 · Cited by 52 · see citing works
“Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway (Xin et al., 2016).”
Background
Irisin counteracts high glucose and fatty acid induced cytotoxicity by preserving AMPK-insulin receptor signaling axis in C2C12 myoblast.
Yano, N., Zhang, L. X., Wei, D., Dubielecka, P., Wei, L., Zhuang, S., Zhu, P., Qin, G., Liu, P., Chin, Y., et al. (2020) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00219.2019 · Cited by 53 · see citing works
Irisin and Autophagy: First Update
Pesce, M., Ballerini, P., Paolucci, T., Puca, I., Farzaei, M. H., & Patruno, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207587 · Cited by 59 · see citing works
Irisin and Incretin Hormones: Similarities, Differences, and Implications in Type 2 Diabetes and Obesity
Marrano, N., Biondi, G., Borrelli, A., Cignarelli, A., Perrini, S., Laviola, L., Giorgino, F., & Natalicchio, A. (2021) · Biomolecules · doi:10.3390/biom11020286 · Cited by 56 · see citing works
“In particular, irisin improves glucose uptake [55,188,192–194] and inhibits gluconeogenesis and glycogenolysis [194], while increasing glycogen storage [188,194] and stimulating FAs oxidation [55,194,195].”
Background
Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo
Amengual, J., García‐Carrizo, F., Arreguín, A., Mušinović, H., Granados, N., Palou, A., Bonet, M. L., & Ribot, J. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000488422 · Cited by 56 · see citing works
Myokines: Metabolic regulation in obesity and type 2 diabetes
Chen, Z.-T., Weng, Z.-X., Lin, J. D., & Meng, Z.-X. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae006 · Cited by 58 · see citing works
“Phosphorylation of AMPK α / insulin receptor β -subunit/ERK1/2 also contributes to the regulation of these effects, which is maintained by irisin [96, 97].”
Irisin: An anti-inflammatory exerkine in aging and redox-mediated comorbidities
Trettel, C. D. S., Pelozin, B. R. D. A., Barros, M. P., Bachi, A. L. L., Braga, P. G. S., Momesso, C. M., Furtado, G. E., Valente, P. A., de Oliveira, E. M., Hogervorst, E., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1106529 · Cited by 55 · see citing works
“In a previous study, hepatic-released irisin was demonstrated to function as a paracrine/autocrine factor that inhibits lipogenesis and gluconeogenesis via the adenosine 5’-monophosphate (AMP)activated protein kinase pathway by reducing the expression of phosphoenolpyruvate carboxyinase (Pepck) and glucose-6phosphate…”
Background
Serum levels of irisin predict short-term outcomes in ischemic stroke
Wu, H., Guo, P., Jin, Z. Y., Li, X., Yang, X., Tang, C., Wang, Y., & Ke, J. (2018) · Cytokine · doi:10.1016/j.cyto.2018.02.017 · Cited by 55 · see citing works
Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes
Biondi, G., Marrano, N., Borrelli, A., Rella, M., Palma, G., CALDERONI, I., Siciliano, E., Lops, P., Giorgino, F., & Natalicchio, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105522 · Cited by 54 · see citing works
High Serum Irisin Level as an Independent Predictor of Diabetes Mellitus
Huh, J. H., Ahn, S. V., Choi, J. H., Koh, S. B., & Chung, C. H. (2016) · Medicine · doi:10.1097/md.0000000000003742 · Cited by 51 · see citing works
Sarcopenia and cachexia: molecular mechanisms and therapeutic interventions
Wang, T., Zhou, D., & Hong, Z. (2025) · MedComm · doi:10.1002/mco2.70030 · Cited by 46 · see citing works
PARP10 (ARTD10) modulates mitochondrial function
Márton, J., Fodor, T., Nagy, L., Vida, A., Kis, G. N., Brunyánszki, A., Antal, M., Lüscher, B., & Bai, P. (2018) · PLoS ONE · doi:10.1371/journal.pone.0187789 · Cited by 49 · see citing works
“In fact, AMPK activation has been shown to enhance fatty acid oxidation [31, 51, 52] that makes it tempting to speculate that PARP10-induced AMPK activation may stand behind enhanced fatty acid oxidation.”
Background
The Impact of Dysmetabolic Sarcopenia Among Insulin Sensitive Tissues: A Narrative Review
Armandi, A., Rosso, C., Caviglia, G. P., Ribaldone, D. G., & Bugianesi, E. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.716533 · Cited by 48 · see citing works
“Another key signaling pathway is represented by the AMPactivated kinase (AMPK), that promotes glucose and FFA uptake/metabolism and modulates long-term responses in mitochondria, by interacting with peroxisome proliferator receptor gamma activator 1a (PGC-1a) (14).”
BackgroundInfluential
Irisin Acts via the PGC-1α and BDNF Pathway to Improve Depression-like Behavior
Jo, D., & Song, J. (2021) · Clinical Nutrition Research · doi:10.7762/cnr.2021.10.4.292 · Cited by 48 · see citing works
“It is found in various organs including the brain, heart, liver, and skeletal muscles [34], and has been reported to control glucose metabolism, lipid metabolism, and energy homeostasis in skeletal muscle and adipose tissues [35-37].”
Background
Irisin ameliorates high glucose‐induced cardiomyocytes injury via AMPK/mTOR signal pathway
Deng, J., Zhang, N., Chen, F., Yang, C., Ning, H., Xiao, C. Y., Sun, K., Liu, Y., Yang, M., Hu, T., et al. (2020) · Cell Biology International · doi:10.1002/cbin.11441 · Cited by 48 · see citing works
“which was reversed by irisin to some extent, which was consistent with the previous study (Xin et al., 2016).”
Result
Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats
Abdou, H. M., Hamaad, F. A., Ali, E. Y., & Ghoneum, M. H. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112838 · Cited by 47 · see citing works
Organokines in disease
(2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2019.07.012 · Cited by 46 · see citing works
Secretomics to Discover Regulators in Diseases
Song, P., Kwon, Y., Joo, J., Kim, D.-G., & Yoon, J. H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163893 · Cited by 45 · see citing works
“In vivo, administration of irisin to high-fat diet (HFD)-fed mice decreased the fasting blood glucose level, and improved glucose and insulin tolerance; the same effects were detected in obese and HFD-fed mice with FNDC5 overexpression [95].”
Background
The Physiological Role of Irisin in the Regulation of Muscle Glucose Homeostasis
Yano, N., Zhao, Y., & Zhao, T. C. (2021) · Endocrines · doi:10.3390/endocrines2030025 · Cited by 46 · see citing works
“Similarly, the enhanced uptake of glucose in the C2C12 cells treated with irisin and cultured in high ambient glucose and PA containing medium were alleviated after the inhibition of the AMPK signaling with AMPKα2 siRNA [62].”
Background
Metformin Protects Against Diabetes-Induced Cognitive Dysfunction by Inhibiting Mitochondrial Fission Protein DRP1
Hu, Y. W., Zhou, Y., Yang, Y., Tang, H., Si, Y., Chen, Z., Shi, Y., & Fang, H. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.832707 · Cited by 44 · see citing works
“Collectively, the findings provide the explanation for the increased oxidative stress and neuronal apoptosis under high glucose conditions (Fossati et al., 2016; Xu et al., 2016).”
Background
Irisin in goldfish ( Carassius auratus ): Effects of irisin injections on feeding behavior and expression of appetite regulators, uncoupling proteins and lipoprotein lipase, and fasting-induced changes in FNDC5 expression
Butt, Z. D., Hackett, J. D., & Volkoff, H. (2017) · Peptides · doi:10.1016/j.peptides.2017.02.003 · Cited by 44 · see citing works
&bgr;‐arrestin‐2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling
Pang, Y.-L., Zhu, H., Xu, J., Yang, L., Liu, L., & Li, J. (2017) · Experimental Cell Research · doi:10.1016/j.yexcr.2017.09.006 · Cited by 35 · see citing works
The Role of Peptide Hormones Discovered in the 21st Century in the Regulation of Adipose Tissue Functions
Kolodziejski, P. A., Pruszyńska‐Oszmałek, E., Wojciechowicz, T., Sassek, M., Leciejewska, N., Jasaszwili, M., Billert, M., Małek, E., Szczepankiewicz, D., Misiewicz-Mielnik, M., et al. (2021) · Genes · doi:10.3390/genes12050756 · Cited by 43 · see citing works
“It was shown that irisin increases fatty acid β-oxidation in muscle tissue [77].”
Background
Berberine demonstrates anti‐inflammatory properties in Helicobacter pylori ‐infected mice with chronic gastritis by attenuating the Th17 response triggered by the B cell‐activating factor
Wu, X., Li, X., Dang, Z., & Jia, Y. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.26681 · Cited by 42 · see citing works
“pylori-infected mice with chronic gastritis mice was established, as described previously.(18,19) Briefly, male C57Bl/6 mice (4 weeks old, 19-21 g) were purchased from Henan Province Hospital of TCM.”
Method
Bioactive proteins and antioxidant peptides from Litsea cubeba fruit meal: Preparation, characterization and ameliorating function on high-fat diet-induced NAFLD through regulating lipid metabolism, oxidative stress and inflammatory response
Li, L., Wang, Y., Zeng, X., Hu, Y. M., Zhang, J., Wang, B., & Chen, S. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136186 · Cited by 41 · see citing works
The role of irisin in metabolic flexibility: beyond adipose tissue browning.
Shen, S.-N., Liao, Q., Chen, X.-P., Peng, C., & Lin, L.-G. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.03.019 · Cited by 36 · see citing works
Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes
Yang, X.-Y., Tse, M. C. L., Hu, X., Jia, W.-H., Du, G., & Chan, C. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000494655 · Cited by 33 · see citing works
Irisin at the crossroads of inter-organ communications: Challenge and implications
Zhao, R. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.989135 · Cited by 40 · see citing works
“Additionally, in diabetic obese C57BL/6 mice, the injection of r-irisin (0.5 µg/g body weight) caused a reduction in Pepck and G6pase expressions in the liver by stimulating the AMPK signaling pathway, and blocking of AMPK signaling decreased the influence of irisin on hepatocytic expressions of Pepck and G6pase (86).”
BackgroundInfluential
Irisin is a biomarker for metabolic syndrome in prepubertal children
Shim, Y. S., Kang, M. J., Yang, S., & Hwang, I. T. (2017) · Endocrine Journal · doi:10.1507/endocrj.ej17-0260 · Cited by 37 · see citing works
Delayed Exercise Training Improves Obesity-Induced Chronic Kidney Disease by Activating AMPK Pathway in High-Fat Diet-Fed Mice
Juszczak, F., Vlassembrouck, M., Botton, O., Zwakhals, T., Decarnoncle, M., Tassin, A., Caron, N., & Declèves, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010350 · Cited by 35 · see citing works
“Interestingly, inhibition of AMPK by a specific inhibitor reduced the effects of Irisin in myocytes and hepatocytes, suggesting that Irisin could be implicated in AMPK pathway regulation [72].”
Background
Mechanism of CNS regulation by irisin, a multifunctional protein
Qi, J., Yang, L.-K., Wang, X., Wang, M., Li, X., Feng, B., Wu, Y., Liu, S., & Zhang, K. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.07.007 · Cited by 36 · see citing works
Reactive Oxygen and Nitrogen Species (RONS) and Cytokines—Myokines Involved in Glucose Uptake and Insulin Resistance in Skeletal Muscle
Llanos, P., & Palomero, J. (2022) · Cells · doi:10.3390/cells11244008 · Cited by 37 · see citing works
Irisin regulates cardiac physiology in zebrafish
Sundarrajan, L., Yeung, C., Hahn, L., Weber, L. P., & Unniappan, S. (2017) · PLoS ONE · doi:10.1371/journal.pone.0181461 · Cited by 35 · see citing works
Relation of serum irisin level with metabolic and antropometric parameters in obese children
Çatlı, G., Küme, T., Tuhan, H., Anık, A., Çalan, Ö. G., Böber, E., & Abacı, A. (2016) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2016.07.019 · Cited by 34 · see citing works
Increased FNDC5 is associated with insulin resistance in high fat‐fed mice
Guilford, B. L., Parson, J. C., Grote, C., Vick, S. N., Ryals, J. M., & Wright, D. (2017) · Physiological Reports · doi:10.14814/phy2.13319 · Cited by 35 · see citing works
“Our results are congruent with previous reports in both animals and humans that suggest the PGC-1aFNDC5/irisin pathway is upregulated in response to chronically elevated blood glucose as well as HOMA-IR (Huh et al. 2012; Kleiner et al. 2012; Crujeiras et al. 2014; Keuper et al. 2014; Yang et al. 2015; Xin et al. 2016;…”
BackgroundResultInfluential
Type 2 diabetes with hypertensive patients results in changes to features of adipocytokines: Leptin, Irisin, LGR4, and Sfrp5
Li, B., Yao, Q., Guo, S., Ma, S., Dong, Y., Xin, H., Wang, H., Liu, L., Chang, W., & Zhang, Y. (2018) · Clinical and Experimental Hypertension · doi:10.1080/10641963.2018.1529779 · Cited by 34 · see citing works
“(8) reported that Irisin ameliorates blood glucose homeostasis through aggrandizing fatty acid oxidation and exploiting glucose adopt by the AMPK signaling pathway in a study on diabetic mice.”
Background
A Comprehensive insight into the effect of chromium supplementation on oxidative stress indices in diabetes mellitus: A systematic review
Kooshki, F., Tutunchi, H., Vajdi, M., Karimi, A., Niazkar, H. R., Shoorei, H., & Gargari, B. P. (2021) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.13462 · Cited by 34 · see citing works
Adipose tissue in older individuals: a contributing factor to sarcopenia
Wang, T., Zhou, D., & Hong, Z. (2024) · Metabolism · doi:10.1016/j.metabol.2024.155998 · Cited by 35 · see citing works
Circulating levels of Irisin in obese individuals at genetic risk for Alzheimer’s disease: Correlations with amyloid-β, metabolic, and neurocognitive indices
Tsai, C., & Pai, M. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.113013 · Cited by 33 · see citing works
High-intensity interval training improved fasting blood glucose and lipid profiles in type 2 diabetic rats more than endurance training; possible involvement of irisin and betatrophin
Amri, J., Parastesh, M., Sadegh, M., Latifi, S. A., & Alaee, M. (2019) · Physiology International · doi:10.1556/2060.106.2019.24 · Cited by 32 · see citing works
“(40) showed that injection of irisin in type 2 diabetes increased GLUT4 in skeletal muscle and decreased enzymes involved in the gluconeogenesis.”
Background
Serum irisin, adropin, and preptin in obese patients 6 months after bariatric surgery
Glück, M., Glück, J., Wiewióra, M., Rogala, B., & Piecuch, J. (2019) · Obesity Surgery · doi:10.1007/s11695-019-03998-y · Cited by 31 · see citing works
The Role of Adipokines and Myokines in the Pathogenesis of Different Obesity Phenotypes—New Perspectives
Pelczyńska, M., Miller‐Kasprzak, E., Piątkowski, M., Mazurek, R., Klause, M., Suchecka, A., Bucoń, M., & Bogdański, P. (2023) · Antioxidants · doi:10.3390/antiox12122046 · Cited by 31 · see citing works
AMP-Activated Kinase (AMPK) Activation by AICAR in Human White Adipocytes Derived from Pericardial White Adipose Tissue Stem Cells Induces a Partial Beige-Like Phenotype
Abdul-Rahman, O., Kristóf, E., Doan‐Xuan, Q., Vida, A., Nagy, L., Horváth, A., Simon, J., Maros, T., Szentkirályi, I., Palotás, L., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157644 · Cited by 31 · see citing works
Vitamin D is associated with metabotropic but not neurotrophic effects of exercise in ovariectomized rats
Babaei, P., Shirkouhi, S. G., Hoseini, R., & Tehrani, B. S. (2017) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-017-0288-z · Cited by 31 · see citing works
“Irisin has been proposed to be secreted by myocytes and adipocytes during exercise [17, 55] and modulates energy expenditure [17] insulin resistance [17] and dyslipidemia [56, 57].”
Background
Reduced plasma level of irisin in first trimester as a risk factor for the development of gestational diabetes mellitus
Wang, P., Ma, H.-H., Hou, X., Song, L., Song, X.-L., & Zhang, J.-F. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.05.038 · Cited by 31 · see citing works
Irisin and Energy Metabolism and the Role of Irisin on Metabolic Syndrome
Aladag, T., Moğulkoç, R., & Baltacı, A. K. (2023) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/1389557523666230411105506 · Cited by 30 · see citing works
Identification of Coenzyme Q10 and Skeletal Muscle Protein Biomarkers as Potential Factors to Assist in the Diagnosis of Sarcopenia
Yen, C., Chang, P., Chang, Y., & Lin, P. (2022) · Antioxidants · doi:10.3390/antiox11040725 · Cited by 30 · see citing works
“Irisin assists in utilizing glucose and stimulates fatty acid oxidation in skeletal muscle tissue [10].”
Background
The saturated fatty acid palmitate induces insulin resistance through Smad3-mediated down-regulation of FNDC5 in myotubes
Guo, Q., Wei, X., Hu, H., Yang, D., Zhang, B., Fan, X., Liu, J., He, H., Oh, Y., Wu, Q., et al. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.10.077 · Cited by 30 · see citing works
Berberine attenuates fructose-induced insulin resistance by stimulating the hepatic LKB1/AMPK/PGC1α pathway in mice
Li, Y., Wang, B., Shen, J.-D., Bai, M., & Xu, E. (2020) · Pharmaceutical Biology · doi:10.1080/13880209.2020.1756349 · Cited by 32 · see citing works
“Therefore, the activation of AMPK has been proposed as an important target for improving insulin sensitivity (Kim et al. 2009; Xin et al. 2016).”
Background

Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes.
Liu, T.-Y., Shi, C.-X., Gao, R., Sun, H.-J., Xiong, X.-Q., Ding, L., Chen, Q., Li, Y.-H., Wang, J.-J., Kang, Y.-M., et al. (2015) · Clinical science · doi:10.1042/cs20150009 · Cited by 352 · see citing works
Irisin ameliorates hepatic glucose/lipid metabolism and enhances cell survival in insulin-resistant human HepG2 cells through adenosine monophosphate-activated protein kinase signaling
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Irisin counteracts high glucose and fatty acid induced cytotoxicity by preserving AMPK-insulin receptor signaling axis in C2C12 myoblast.
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Metformin promotes irisin release from murine skeletal muscle independently of AMP ‐activated protein kinase activation
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Irisin alleviates FFA induced β-cell insulin resistance and inflammatory response through activating PI3K/AKT/FOXO1 signaling pathway
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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
ORCID: Xin, C
Liu, J
Zhang, J
Zhu, D
Wang, H
Xiong, L
Lian, K
Xu, C
Zhang, L
Liu, Y
Tao, L
Venue: International Journal of Obesity
Publisher: Springer Science and Business Media LLC
Published: 2015-09-25
Volume: 40
Issue: 3
Pages: 443-451
ISSN: 0307-0565 (ISSN-L)
1476-5497
DOI: 10.1038/ijo.2015.199
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: International Journal of Obesity (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Physiology › 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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Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway

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