Irisin Is Regulated by CAR in Liver and Is a Mediator of Hepatic Glucose and Lipid Metabolism

Mo, Li; Shen, Jing; Liu, Qinhui; Zhang, Yuwei; Kuang, Jiangying; Pu, Shiyun; Cheng, Shihai; Zou, Min; Jiang, Wei; Jiang, Changtao; Qu, Aijuan; He, Jinhan

doi:10.1210/me.2015-1292

Cited by 70 publications

(55 citation statements)

References 33 publications

(42 reference statements)

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“…Upregulated serum irisin levels in the face of unchanged skeletal muscle Fndc5 mRNA levels in ATRA-treated mice prompted us to analyze Fndc5 gene expression in additional tissues that have been recently demonstrated to be a source of irisin, namely adipose tissues [5, 35] and the liver [36], and to examine FNDC5 protein by immunohistochemistry in all of them. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Amengual

García-Carrizo

Arreguín

et al. 2018

Cell Physiol Biochem

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Background/Aims: All-trans retinoic acid (ATRA) has protective effects against obesity and metabolic syndrome. We here aimed to gain further insight into the interaction of ATRA with skeletal muscle metabolism and secretory activity as important players in metabolic health. Methods: Cultured murine C2C12 myocytes were used to study direct effects of ATRA on cellular fatty acid oxidation (FAO) rate (using radioactively-labelled palmitate), glucose uptake (using radioactively-labelled 2-deoxy-D-glucose), triacylglycerol levels (by an enzymatic method), and the expression of genes related to FAO and glucose utilization (by RT-real time PCR). We also studied selected myokine production (using ELISA and immunohistochemistry) in ATRA-treated myocytes and intact mice. Results: Exposure of C2C12 myocytes to ATRA led to increased fatty acid consumption and decreased cellular triacylglycerol levels without affecting glucose uptake, and induced the expression of the myokine irisin at the mRNA and secreted protein level in a dose-response manner. ATRA stimulatory effects on FAO-related genes and the Fndc5 gene (encoding irisin) were reproduced by agonists of peroxisome proliferator-activated receptor β/δ and retinoid X receptors, but not of retinoic acid receptors, and were partially blocked by an AMP-dependent protein kinase inhibitor. Circulating irisin levels were increased by 5-fold in ATRA-treated mice, linked to increased Fndc5 transcription in liver and adipose tissues, rather than skeletal muscle. Immunohistochemistry analysis of FNDC5 suggested that ATRA treatment enhances the release of FNDC5/irisin from skeletal muscle and the liver and its accumulation in interscapular brown and inguinal white adipose depots. Conclusion: These results provide new mechanistic insights on how ATRA globally stimulates FAO and enhances irisin secretion, thereby contributing to leaning effects and improved metabolic status.

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Section: Resultsmentioning

confidence: 99%

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Amengual

García-Carrizo

Arreguín

et al. 2018

Cell Physiol Biochem

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“…It is important that FNDC5/irisin regulation was reported in mouse liver, but its expression was not changed in skeletal muscle or adipose tissue. According to prominent studies, CAR is mainly expressed in the liver and intestine (3).…”

Section: Discussionmentioning

confidence: 99%

“…The liver stores energy as glycogen and stores digested triglycerides in the form of fatty acids (2). On the contrary, the accumulation of excessive triglyceride in the liver can result in hepatic steatosis (3). Adiposity can be seen either in the form of white adipose tissue or brown adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

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The Effects of Resistance and Endurance Training on the Liver Tissue FNDC5 mRNA Gene Expression in Male Rats

Rashidlamir

Hoseinzadeh

Dashtkhaki

2017

Ann. Appl. Sport Sci

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Background. The accumulation of excess triglyceride in the liver and a decrease in brown adipose tissue is related to the fatty liver disease. Regular physical activity can take part in regulating fat oxidation and inhibiting fat accumulation by creating and releasing some myokines. Nevertheless, the effectiveness of each training method in this regard is still not certain. Objective(s). This study aims at comparing the effects of resistance and endurance training on FNDC5 (the precursor of irisin myokine) gene expression in male rat liver tissues.. Methods. Fifteen Wistar male rats (aged 10-12 weeks with an average weight of 331.8 ±63.09 gr) were used. After being taken to the animals' laboratory, the subjects were randomly assigned to three equal groups viz: control (N=5), endurance (N=5) and resistance (N=5). For the purpose of tissue sampling, all these subjects were anesthetized 72 hours after the experiment had been completed. The liver tissue was immediately removed and then quickly frozen in liquid nitrogen and kept at a temperature of -80o C until RNA extraction. FNDC5 relative gene expression was identified by Real-time PCR method. Results. Data analysis revealed a significant difference in FNDC5 gene expression among the groups (P=0.008, Chi Square=31.791). No significant difference was observed between the resistance training and endurance training groups in FNDC5 gene expression, though (P=0.959). Conclusion. It can be established that both resistance and endurance training can similarly affect the production and secretion of exerciseinduced myokines, including FNDC5 irisin, which can in turn protect against obesity and its impacts on the liver tissue by stimulating the process of browning of white fat.

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“…In addition, irisin effects on carbohydrate and lipid metabolism also have been provided for the liver (Mo et al 2016) suggesting broader effects on energy metabolism. Our marathon mouse model DUhTP, established by long-term selection for high treadmill performance, is characterized by increased hepatic lipogenesis on one hand and peripheral obesity on the other, if compared to unselected control mice (DUC) (Brenmoehl et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Browning of subcutaneous fat and higher surface temperature in response to phenotype selection for advanced endurance exercise performance in male DUhTP mice

et al. 2016

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For the assessment of genetic or conditional factors of fat cell browning, novel and polygenic animal models are required. Therefore, the long-term selected polygenic mouse line DUhTP originally established in Dummerstorf for high treadmill performance is used. DUhTP mice are characterized by increased fat accumulation in the sedentary condition and elevated fat mobilization during mild voluntary physical activity. In the present study, the phenotype of fat cell browning of subcutaneous fat and a potential effect on oral glucose tolerance, an indicator of metabolic health, were addressed in DUhTP mice. Analysis of peripheral fat pads revealed increased brite (brown-in-white) subcutaneous adipose tissues and in subcutaneous fat from DUhTP mice higher levels of irisin and different markers of fat cell browning like T-box transcription factor (Tbx1), PPARα, and uncoupling protein (UCP1) (P < 0.05) when compared to unselected controls. UCP1 was further increased in subcutaneous fat from DUhTP mice in response to mild exercise (fourfold, P < 0.05). In addition, surface temperature of DUhTP mice was increased when compared to controls indicating a physiological effect of increased UCP1 expression. The present study suggests that DUhTP mice exhibit different markers of mitochondrial biogenesis and fat browning without external stimuli. At an age of 43 days, sedentary DUhTP mice have improved metabolic health as judged from lower levels of blood glucose after an oral glucose tolerance test. Consequently, the non-inbred mouse model DUhTP represents a novel model for the identification of fat cell browning mechanisms in white adipose tissues.

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Irisin Is Regulated by CAR in Liver and Is a Mediator of Hepatic Glucose and Lipid Metabolism

Cited by 70 publications

References 33 publications

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

Retinoic Acid Increases Fatty Acid Oxidation and Irisin Expression in Skeletal Muscle Cells and Impacts Irisin In Vivo

The Effects of Resistance and Endurance Training on the Liver Tissue FNDC5 mRNA Gene Expression in Male Rats

Browning of subcutaneous fat and higher surface temperature in response to phenotype selection for advanced endurance exercise performance in male DUhTP mice

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