GENERAL AND COMPARATIVE ENDOCRINOLOGY
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2020
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IF 2.428
Liping Yang,Shaoyang Zhi,Guokun Yang,Chaobin Qin,Wenli Zhao,Mingming Niu,Wenlei Zhang,Wenyu Tang,Xiao Yan,Yuru Zhang,Xiaolin Meng,Ronghua Lu,Guoxing Nie
Irisin, encoded by fibronectin type III domain-containing protein 5 (FNDC5) gene, plays a role in energy expenditure and insulin sensitivity in mice. In fish, the function of irisin related to glucose metabolism is less reported. It may increase glucose utilization in fish. The aim of the present study was to characterize the regulatory role of irisin in glucose metabolism in common carp ( Cyprinus carpio L.). In this study, FNDC5a and FNDC5b were isolated from common carp. The cDNA of FNDC5a and FNDC5b were 722 bp and 714 bp, encoding 221 and 207 amino acids, respectively. FNDC5a was abundantly expressed in the brain and gonad. FNDC5b was mainly expressed in brain. Different expression pattern of FNDC5a and FNDC5b under fasting/refeeding and OGTT experiment were identified. The recombinant common carp irisinA and irisinB were prepared by prokaryotic expression system. Glucose concentration was decreased in treatment with irisinA or irisinB in the in vitro and in vivo experiments. The mRNA expression levels of gluconeogenesis-related genes were significantly down-regulated, while the mRNA expression of glycolysis-related genes were significantly up-regulated after treatment with recombinant irisinA or irisinB in liver in vivo and in primary hepatocytes in vitro. Our research shows that irisin inhibits hepatic gluconeogenesis and promotes hepatic glycolysis. Taken together, this study for the first time revealed the two subtypes of FNDC5 and explored the function and mechanisms of irisinA and irisinB in fish glucose homeostasis.
研究领域:
分子生物学
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内分泌学
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水产养殖
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产品关联
DOI
PubMed
高影响因子
Cardiovascular Diabetology
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2024
·Vol. 23
·期 1
·1-19
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IF 8.5
Tang Yuan-juan,Zhang Zhen,Yan Tong,Chen Ken,Xu Guo-fan,Xiong Shi-qiang,Wu Dai-qian,Chen Jie,Jose Pedro A.,Zeng Chun-yu,Fu Jin-juan
Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 1 diabetes mellitus (T1DM), which still lacks adequate therapy. Irisin, a cleavage peptide off fibronectin type III domain-containing 5, has been shown to preserve cardiac function in cardiac ischemia–reperfusion injury. Whether or not irisin plays a cardioprotective role in DCM is not known. Methods and results T1DM was induced by multiple low-dose intraperitoneal injections of streptozotocin (STZ). Our current study showed that irisin expression/level was lower in the heart and serum of mice with STZ-induced TIDM. Irisin supplementation by intraperitoneal injection improved the impaired cardiac function in mice with DCM, which was ascribed to the inhibition of ferroptosis, because the increased ferroptosis, associated with increased cardiac malondialdehyde (MDA), decreased reduced glutathione (GSH) and protein expressions of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), was ameliorated by irisin. In the presence of erastin, a ferroptosis inducer, the irisin-mediated protective effects were blocked. Mechanistically, irisin treatment increased Sirtuin 1 (SIRT1) and decreased p53 K382 acetylation, which decreased p53 protein expression by increasing its degradation, consequently upregulated SLC7A11 and GPX4 expressions. Thus, irisin-mediated reduction in p53 decreases ferroptosis and protects cardiomyocytes against injury due to high glucose. Conclusion This study demonstrated that irisin could improve cardiac function by suppressing ferroptosis in T1DM via the SIRT1-p53-SLC7A11/GPX4 pathway. Irisin may be a therapeutic approach in the management of T1DM-induced cardiomyopathy.
研究领域:
内分泌学
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心脏病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2024
·
IF 14.3
Xia Zhang,Lijia Liang,Fengxian Wang,Pedro A. Jose,Ken Chen,Chunyu Zeng
Acute kidney injury (AKI) is the sudden decrease in renal function that can be attributed to dysregulated reactive oxygen species (ROS) production and impaired mitochondrial function. Irisin, a type I membrane protein secreted by skeletal muscles in response to physical activity, has been reported to alleviate kidney damage through regulation of mitochondrial biogenesis and oxidative metabolism. In this study, a macrophage membrane-coated metal-organic framework (MCM@MOF) is developed as a nanocarrier for encapsulating irisin to overcome the inherent characteristics of irisin, including a short circulation time, limited kidney-targeting ability, and low membrane permeability. The engineered irisin-mediated biomimetic nanotherapeutics have extended circulation time and enhanced targeting capability toward injured kidneys due to the preservation of macrophage membrane proteins. The irisin-encapsulated biomimetic nanotherapeutics effectively mitigate acute ischemia-reperfusion injury by protecting mitochondrial function and modulating SOD2 levels in renal tubular epithelial cells. The present study provides novel insights to advance the development of irisin as a potential therapeutic approach for AKI.
研究领域:
纳米技术
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药学
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肾脏生理学
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分子生物学
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DOI
PubMed
高影响因子
MATERIALS & DESIGN
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2023
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IF 8.4
Kai Li,Bailong Tao,Hongchuan Tian,Junjie Wu,Ke Huang,Caiping Yan,Sinan Chen,Ai Guo,Dianming Jiang
Accelerated population ageing has brought a great burden to the development of society. Repairing senile osteoporosis fractures is a great challenge, but a desirable way to address this issue is by developing multifunctional titanium(Ti) implants with antiaging and pro-osteogenic effects. Herein, to endow TI substrate with an antiaging effect for enhanced bone formation, an exercise-induced myokine(irisin) was loaded on titanium dioxide nanotubes(TNTs) and then a multilayered structure composed of chitosan(Chi) and gelatin(Gel) was constructed on the substrates via a layer-by-layer-assembly technique(TNT-IR-LBL). The surface topography of TNT-IR-LBL was characterized by scanning electron microscopy (SEM), atomic force microscopy(AFM), X-ray photoelectron spectroscopy(XPS) and water contact angle measurements, respectively. As an exercise-induced myokine, the irisin secreted from skeletal muscle exhibits strong activity for against the chronic diseases. The implants synthesized here displayed good biocompatibility towards osteoblasts. Moreover, irisin was sustainably released from TNT-IR-LBL for more than 3 weeks. In vitro studies indicated the TNT-IR-LBL substrates promoted osteoblast differentiation. In addition, compared to bare titanium, TNT-IR-LBL significantly promoted new bone formation around the implant interface in senile osteoporosis rats 4 weeks after implantation. Overall, this study provides a promising candidate to develop Ti-based orthopaedic implants to repair senile osteoporosis fractures.
研究领域:
生物材料
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生物医学工程
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骨科
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老年学
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DOI
高影响因子
Neuroscience Bulletin
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2022
·Vol. 38
·期 11
·1347-1364
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IF 5.271
Yu Jie,Cheng Yao,Cui Yaru,Zhai Yujie,Zhang Wenshen,Zhang Mengdi,Xin Wenyu,Liang Jia,Pan Xiaohong,Wang Qiaoyun,Sun Hongliu
An increased level of reactive oxygen species is a key factor in neuronal apoptosis and epileptic seizures. Irisin reportedly attenuates the apoptosis and injury induced by oxidative stress. Therefore, we evaluated the effects of exogenous irisin in a kainic acid (KA)-induced chronic spontaneous epilepsy rat model. The results indicated that exogenous irisin significantly attenuated the KA-induced neuronal injury, learning and memory defects, and seizures. Irisin treatment also increased the levels of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), which were initially reduced following KA administration. Furthermore, the specific inhibitor of UCP2 (genipin) was administered to evaluate the possible protective mechanism of irisin. The reduced apoptosis, neurodegeneration, and spontaneous seizures in rats treated with irisin were significantly reversed by genipin administration. Our findings indicated that neuronal injury in KA-induced chronic epilepsy might be related to reduced levels of BDNF and UCP2. Moreover, our results confirmed the inhibition of neuronal injury and epileptic seizures by exogenous irisin. The protective effects of irisin may be mediated through the BDNF-mediated UCP2 level. Our results thus highlight irisin as a valuable therapeutic strategy against neuronal injury and epileptic seizures.
研究领域:
神经科学
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药理学
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分子生物学
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癫痫研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cellular Neuroscience
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2021
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IF 5.505
Cheng Yao,Cui Yaru,Zhai Yujie,Xin Wenyu,Yu Yan,Liang Jia,Li Shucui,Sun Hongliu
Elevated reactive oxygen species (ROS) level is considered a crucial causative factor for neuronal damage in epilepsy. Irisin has been reported to ameliorate mitochondrial dysfunction and to reduce ROS levels; therefore, in this study, the effect of exogenous irisin on neuronal injury was evaluated in rats with kainic acid (KA)-induced status epilepticus (SE). Our results showed that exogenous irisin treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF) and uncoupling protein 2 (UCP2), and reduced the levels of neuronal injury and mitochondrial oxidative stress. Additionally, an inhibitor of UCP2 (genipin) was administered to investigate the underlying mechanism of irisin-induced neuroprotection; in rats treated with genipin, the neuroprotective effects of irisin on KA-induced SE were found to be partially reversed. Our findings confirmed the neuroprotective effects of exogenous irisin and provide evidence that these effects may be mediated via the BDNF/UCP2 pathway, thus providing valuable insights that may aid the development of exogenous irisin treatment as a potential therapeutic strategy against neuronal injury in epilepsy.
研究领域:
神经科学
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药理学
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神经保护
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Chunyu Wang,Kunjing Liu,Jing Ji,Wenyuan Ma,Haojia Zhang,Kai Wang,Yukun Lin,Chongyang Ma,Xueqian Wang,Fafeng Cheng
Background Metabolic dysfunction-associated fatty liver disease (MAFLD) is a major global chronic liver disorder, with metabolic dysfunction-associated steatohepatitis (MASH) representing its severe subtype. Liu-Jun-Zi Decoction (LJZD), a classical traditional Chinese medicine (TCM) formula, has shown clinical efficacy against MASH, however, its underlying mechanisms remain unclear. Purpose To investigate the molecular mechanism through which LJZD alleviates hepatic steatosis in MASH mice by restoring irisin secretion in skeletal muscle. Methods A MASH mouse model was established using a methionine and choline deficient (MCD) diet, followed by LJZD treatment. First, major chemical components of LJZD were identified via UHPLC-QE-MS. Subsequently, histopathological and biochemical analyses were performed to evaluate the effects of LJZD on MASH and skeletal muscle atrophy. Finally, the secretion of irisin in skeletal muscle was assessed, and bioinformatics analysis was used to screen downstream targets of irisin. Results LJZD significantly alleviated hepatic steatosis, injury, inflammation, and fibrosis in MASH mice while improving concomitant skeletal muscle atrophy. Furthermore, LJZD enhanced irisin secretion from skeletal muscle. Integrated transcriptomic analysis identified carboxylesterase 2A (CES2A) as a key hepatic downstream effector of irisin. Conclusion LJZD ameliorates MASH by promoting skeletal muscle irisin secretion, which upregulates hepatic CES2A to enhance lipid catabolism. In summary, current data extend the research scope on LJZD's pharmacological effects and suggest new approaches for clinical MASH treatment. LJZD alleviates hepatic steatosis by targeting skeletal muscle, indicating its potential as a therapeutic candidate for MASH.
研究领域:
中医药学
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药理学
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肝病学
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分子生物学
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代谢疾病
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Food & Function
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2021
·Vol. 12
·期 14
·6490-6501
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IF 5.396
Ao Sun,Xiaoqin Hu,Huijian Chen,Yulan Ma,Xiyue Yan,Dangsheng Peng,Jie Ping,Youe Yan
Ursolic acid (UA) shows an effect on obesity and related metabolic diseases, but its mechanism of action remains unclear. We found that UA clearly reduced the body weight and adipose tissue mass and improved the glucose tolerance and insulin sensitivity in obese male mice. UA treatment significantly reduced the volume and weights of the epididymal white adipose tissue (eWAT) and inguinal subcutaneous white adipose tissue (igSWAT) of HFD-fed mice, respectively. UA also decreased the expression of genes involved in adipocyte differentiation and lipogenesis in igSWAT. Real-time PCR and immunohistochemistry showed that the expression of beiging-related genes 4-1BB factor (CD137), T-box transcription factor 1 (TBX1), and transmembrane protein 26 (TMEM26) were significantly increased in the UA treatment group. UA treatment significantly reduced the weight of gastrocnemius muscle (GM) and lipid droplets in the GM. UA treatment significantly upregulated the expression of PR domain-containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and fibronectin type 3 domain-containing protein 5 (FNDC5) in GM and igSWAT. UA also stimulated irisin secretion in the serum. In conclusion, these results indicate that UA plays an anti-obesogenic role by increasing the secretion of irisin and promoting the beiging of WAT.
研究领域:
药理学
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代谢
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肥胖研究
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产品关联
DOI
PubMed
高影响因子
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