Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

Vliora, Maria; Grillo, Elisabetta; Corsini, Michela; Ravelli, Cosetta; Nintou, Eleni; Karligiotou, Eleni; Flouris, Andreas D.; Mitola, Stefania

doi:10.1016/j.bbagen.2022.130085

Cited by 23 publications

(14 citation statements)

References 49 publications

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“…Vliora et al [ 25 ] recently revealed that irisin has a time-dependent role in the induction of mitochondrial NST, oxidative capability, lipolysis regulation, and EE in adipocytes. Irisins’ action is thought to be related to modification of multiple irisin downstream pathways, including PI3K-AKT, nuclear factor kappa B, and cAMP-response element binding protein [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

et al. 2022

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The prevalence of obesity and its associated metabolic disorders, along with their healthcare costs, is rising exponentially. Irisin, an adipomyokine, may serve as a critical cross-organ messenger, linking skeletal muscle with adipose tissue and the liver to integrate the energy homeostasis under diet-induced obesity. We aimed to explore the putative role of irisin in the protection against obesity in a postmenopausal rat model by modulating energy expenditure (EE). Bilateral ovariectomy (OVX) was performed. After 3 weeks of recovery, the OVX rats were classified according to their dietary protocol into rats maintained on normal diets (ND) (OVX) or high-fat diet (HFD) groups. The HFD-fed animals were equally divided into OVX/HFD, or irisin-treated OVX/HFD groups. Sham rats, maintained on ND, were selected as the control group. We evaluated anthropometric, EE, and molecular biomarkers of browning and thermogenesis in inguinal white adipose tissue and skeletal muscle, and the activity of the proteins related to mitochondrial long chain fatty acid transport, oxidation, and glycolysis. HFD of OVX further deteriorated the disturbed glucose homeostasis, lipid profile, and the reduced irisin, thermogenic parameters in adipose tissue and skeletal muscle, and EE. Irisin treatment improved the lipid profile and insulin resistance. That was associated with reduced hepatic gluconeogenic enzyme activities and restored hepatic glycogen content. Irisin reduced ectopic lipid infiltration. Irisin augmented EE by activating non-shivering thermogenesis in muscle and adipose tissues and decreasing metabolic efficiency. Our experimental evidence suggests irisin’s use as a potential thermogenic agent, therapeutically targeting obesity in postmenopausal patients. Graphical abstract Irisin modulates the non-shivering thermogenesis in skeletal muscle and adipose tissue in postmenopausal model

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Section: Discussionmentioning

confidence: 99%

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

et al. 2022

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“…The loss of muscle mass can lead to a decreased amount of irisin in the circulation or in the affected tissues [ 66 ]. Irisin, on the other hand, can increase the expression of uncoupling protein 1, a protein that increases thermogenesis and energy consumption in adipose tissue [ 67 ]. Indeed, Castro et al [ 27 ] showed that changes in myokines may induce tumor evasion and inflammation.…”

Section: Discussionmentioning

confidence: 99%

Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis

Vliora

Nintou

Karligiotou

et al. 2022

IJMS

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Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic cleavage. Recently it has been the topic of investigation in several types of cancer. In this study, we conducted a systematic review and meta-analysis to investigate its implication in different types of cancer. Our results suggest that irisin expression is decreased in cancer patients, thus it can be used as a valid biomarker for the diagnosis of several types of cancer. In addition, our results indicate that irisin may have an important role in tumor progression and metastasis since it is involved in multiple signaling pathways that promote cell proliferation and migration.

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“…FNDC5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway involved in browning of white adipocytes is thought to be mitogenactivated protein kinase (MAPK) signaling pathways, and other essential functions of FNDC5/irisin are mediated through additional pathways including the AMP-activated protein kinase (AMPK) pathway, PI3K/AKT, and STAT3/Snail [21,22]. By binding to an α-integrin receptor [23], irisin is capable of driving brown-like adipocytes through the activation of the p38 MAPK and extracellular signal-related kinase (ERK) pathways, ameliorating obesity and glucose homeostasis in obese mice [20,24].…”

Section: Introductionmentioning

confidence: 99%

Pentamethylquercetin Regulates Lipid Metabolism by Modulating Skeletal Muscle-Adipose Tissue Crosstalk in Obese Mice

et al. 2022

Pharmaceutics

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Irisin is an exercise-induced hormone that regulates lipid metabolism. The present study investigates whether the anti-obesity effect of the natural flavonoid pentamethylquercetin (PMQ) is related to irisin secretion from skeletal muscle in whole animals and cultured cells. Obese mice induced by monosodium glutamate were administered oral PMQ to determine blood irisin level and in vivo parameters of lipid metabolism, and cultured mouse C2C12 myoblasts and 3T3-L1 preadipocytes were employed to investigate the related molecular identities. PMQ increased circulating irisin and decreased bodyweight, insulin, and lipid levels accompanied with increasing brown-like adipocyte formation in obese mice. The brown adipocyte marker uncoupling protein 1 (UCP-1) and other brown-like adipocyte-specific genes and/or markers were increased in mouse white fat tissue, while PMQ treatment reversed the above changes. PMQ also dose-dependently increased the reduced levels of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and fibronectin type III domain-containing 5 (FNDC5) signal molecules in obese mice. Interestingly, the irisin level was increased in the culture medium of C2C12 cells treated with PMQ, and the conditioned medium stimulated the brown-like transition of 3T3-L1 preadipocytes with the increased expression of PGC-1α, FNDC5, UCP-1, and other brown-like adipocyte-specific genes. The effects of conditioned culture medium were abolished in C2C12 cells with silenced PGC-1α. On the other hand, PMQ-induced upregulation of PGC-1α and FNDC5 expression was reduced by AMPK inhibitor Compound C in C2C12 cells. Our results demonstrate the novel information that PMQ-induced irisin secretion from skeletal muscle involves the improvement of metabolic dysfunction in obese mice via activating the AMPK/PGC-1α/FNDC5 signal pathway, suggesting that PMQ modulates skeletal muscle-adipose tissue crosstalk and may be a promising drug candidate for treating obesity and obesity-related metabolic diseases.

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Irisin regulates thermogenesis and lipolysis in 3T3-L1 adipocytes

Cited by 23 publications

References 49 publications

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

Irisin improves adiposity and exercise tolerance in a rat model of postmenopausal obesity through enhancing adipo-myocyte thermogenesis

Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis

Pentamethylquercetin Regulates Lipid Metabolism by Modulating Skeletal Muscle-Adipose Tissue Crosstalk in Obese Mice

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