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fibroblast growth factor 21 in dairy cows:current knowledge and potential relevance

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Journal of Animal Science and Biotechnology 2022年第2期13卷 303-315页

作者： Klaus Eder Denise K.Gessner Robert Ringseis Institute of Animal Nutrition and Nutrition Physiology Justus-Liebig-University GiessenHeinrich-Buff-Ring 26-3235392 GiessenGermany

fibroblast growth factor 21(FGF21)has been identified as an important regulator of carbohydrate and lipid metabolism,which plays an important role for metabolic regulation,particularly under conditions of energy deprivation or stress *** cows are subjected to a negative energy balance and various kinds of stress particularly during the periparturient phase and during early *** has been shown that the plasma concentration of FGF21 in dairy cows is dramatically increased at parturition and remains high during the first weeks of *** finding suggests that FGF21 might exert similar functions in dairy cows than in other species,such as mice or ***,the role of FGF21 in dairy cows has been less investigated so *** a brief summary of the previous findings about the function of FGF21 in humans and mice,the present review aims to present the current state of knowledge about the role of FGF21 in dairy *** first part of the review deals with the tissue localization of FGF21 and with conditions leading to an upregulation of FGF21 expression in the liver of dairy *** the second part,the influence of nutrition on FGF21 expression and the role of FGF21 for metabolic diseases in dairy cows is *** the third part,findings of exogenous FGF21 application on metabolism in dairy cows are ***,the potential relevance of FGF21 in dairy cows is *** is concluded that FGF21 might be of great importance for metabolic adaptation to negative energy balance and stress conditions in dairy ***,further studies are needed for a better understanding of the functions of FGF21 in dairy cows.

关键词： Dairy cow Energy deprivation fibroblast growth factor 21 Metabolic adaptation Stress

fibroblast growth factor 21 and dietary interventions: what we know and what we need to know next

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Medical Review 2022年第5期2卷 524-530页

作者： Tianru Jin Division of Advanced Diagnostics Toronto General Hospital Research InstituteUniversity Health Network101 College St.Toronto M5G 1L7Canada Banting and Best Diabetes Centre Temerty Faculty of MedicineUniversity of TorontoTorontoM5G 2C4Canada Department of Physiology Temerty Faculty of MedicineUniversity of TorontoToronto M5S 1A8Canada

Dietary interventions include the change of dietary styles,such as fasting and dietary or nutrient restrictions;or the addition of plant-derived compounds(such as polyphenols known as curcumin,resveratrol,or anthocyanin,or other nutraceuticals)into the *** the past a few decades,large number of studies have demonstrated therapeutic activities of these dietary interventions on metabolic and other diseases in human subjects or various animal *** underlying those versatile therapeutic activities,however,remain largely ***,recent studies have shown that fibroblast growth factor 21(FGF21),a liver-derived hormone or hepatokine,mediates metabolic beneficial effects of certain dietary polyphenols as well as protein *** I have briefly summarized functions of FGF21,highlighted related dietary interventions,and presented literature discussions on role of FGF21 in mediating function of dietary polyphenol intervention and protein *** is followed by presenting my perspective view,with the involvement of gut *** is anticipated that further breakthroughs in this field in the near future will facilitate conceptual merge of classical medicine and modern medicine.

关键词： dietary polyphenol intervention fibroblast growth factor 21 gut microbiota protein restriction.

fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells

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Chinese Medical Journal 2010年第23期123卷 3417-3421页

作者： Lv Yun LIU Jing-hua ZHANG Li-ke DU Jie ZENG Xiang-jun HAO Gang HUANG Ji ZHAO Dong-hui WANG Guo-zhong ZHANG Ying-chuan Department of Cardiology Beijing Anzhen Hospital CapitalMedical University Beijing 100029 China Department of Pathophysiology Capital Medical UniversityBeijing 100069 China

Background fibroblast growth factor 21 （FGF21） is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection *** The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein （ox-LDL）, and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells （CMECs） were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMFCs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 *** The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 μmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis （P ＜0.05）.Conclusions FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.

关键词： fibroblast growth factor 21 oxidized-low density lipoprotein atherosclerosis endothelial dysfunction

Depletion of gut microbiota facilitates fibroblast growth factor 21-mediated protection against acute pancreatitis in diabetic mice

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World Journal of Diabetes 2023年第12期14卷 1824-1838页

作者： Qi-Yan Sun Xu-Ye Wang Zu-Pin Huang Jing Song En-Dong Zheng Fang-Hua Gong Xiao-Wang Huang School of Pharmacy Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina Zhejiang Medical Products Service Center Hangzhou 310012Zhejiang ProvinceChina Department of Hepatobiliary and Pancreatic Surgery The Affiliated Cangnan Hospital of Wenzhou Medical UniversityWenzhou 325800Zhejiang ProvinceChina

BACKGROUND fibroblast growth factor 21(FGF21),primarily secreted by the pancreas,liver,and adipose tissues,plays a pivotal role in regulating glucose and lipid *** pancreatitis(AP)is a common inflammatory disease with specific clinical *** patients with diabetes present with concurrent inflammatory *** exacerbates intestinal permeability and intestinal inflammation,thus leading to the progression to *** previous study indicated that FGF21 significantly attenuated susceptibility to AP in *** To investigate the potential protective role of FGF21 against AP in diabetic *** In the present study,a mouse model of AP was established in diabetic(db)/db diabetic mice through ceruletide ***,the protective effects of recombinant FGF21 protein against AP were evaluated,with an emphasis on examining serum amylase(AMS)levels and pancreatic and intestinal inflammatory cytokines[interleukin(IL)-6,tumor necrosis factor-alpha(TNF-),and intestinal IL-1β].Additionally,the impact of this treatment on the histopathologic changes of the pancreas and small intestinal was examined to elucidate the role of FGF21 in diabetic mice with *** antibiotic(Abx)cocktail was administered in combination with FGF21 therapy to investigate whether the effect of FGF21 on AP in diabetic mice with AP was mediated through the modulation of the gut microbiota. Subsequently, thePhylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), a bioinformaticssoftware package, was used to predict different pathways between the groups and to explore the potentialmechanisms by which the gut microbiota influenced the protective effect of *** results indicated that FGF21 notably diminished the levels of serum AMS (944.5 ± 15.9 vs 1732 ± 83.9, P factors including IL-6 (0.2400 ± 0.55 vs 1.233 ± 0.053, P < 0.01), TNF- (0.7067 ± 0.22 vs 1.433 ±0.051, P < 0.01), and IL-1β (1.377 ±

关键词： Acute pancreatitis fibroblast growth factor 21 Gut microbiota Diabetes PICRUSt2 Cocktail of antibiotics

Protection Effect of Exogenous fibroblast growth factor 21 on the Kidney Injury in Vascular Calcification Rats

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Chinese Medical Journal 2018年第5期131卷 532-538页

作者： Yu-Chen Shi Wei-Wei Lu Yue-Long Hou Kun Fu Feng Gan Shu-Juan Cheng Shao-Ping Wang Yong-Fen Qi Jing-Hua Liu Department of Cardiology Beijing Anzhen Hospital Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing 100029 China Department of Physiology Xuzhou Medical University Xuzhou Jiangsu 221004 China Department of Pharmacology and Nutritional Sciences University of Kentucky Lexington Kentucky USA Key Laboratory of Molecular Cardiovascular Science Ministry of Education Peking University Health Science Center Beijing 100191 China Department of Cardiology Beijing Aerospace General Hospital Beijing 100076 China

Background： Chronic kidney disease （CKD） is closely related to the cardiovascular events in vascular calcification （VC）. However, little has known about the characteristics of kidney injury caused by VC. fibroblast growth factor 21 （FGF21 ） is an endocrine thctor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases, Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats. Methods： The male Sprague-Dawley rats were divided into three groups：（ 1 ） control group, （2） Vitamin D3 plus nicotine （VDN）-induced VC group, （3） FGF21-treated VDN group. After 4 weeks, the rats were killed and the blood was collected for serum creatinine, urea nitrogen, calcium, and phosphate measurement. Moreover, the renal tissues were homogenized for alkaline phosphatases （ALPs） activity and calcium content. The levels of FGF21 protein were measured by radioimmunoassay. The levels of β-Klotho and FGF receptor 1 （FGFR1） protein were measured by enzyme-linked immunosorbent assay （EL1SA）. The structural damage and calcifications in aortas were stained by Alizarin-red S. Moreover, the structure of kidney was observed by hematoxylin and eosin staining. Results： The renal lhnction impairment caused by VDN modeling was ameliorated by FGF21 treatment, inhibited the elevated serum creatinine and urea level by 20.5% （34.750 ± 4.334 pmol/L vs. 27.630± 2.387pamol/L） and 4.0% （7.038 ± 0.590 mmol/L vs. 6.763 ±0.374 mmol/L; P 〈 0.01 ）, respectively, together with the structural damages of glomerular atrophy and renal interstitial fibrosis. FGF21 treatment downregulated the ALP activity, calcium content in the kidney of VC rats by 42.1% （P 〈 0.01 ） and 11.7% （P 〈 0.05） as well as ameliorated the aortic injury and calcification as compared with VDN treatment alone group, indicating an ameliorative effect on VC. EL1SA assays showed that the

关键词： Chronic fibroblast growth factor 21 Renal Insufficiency Vascular Calcification β-Klotho

Leukocyte cell-derived chemotaxin-2 and fibroblast growth factor 21 in alcohol-induced liver cirrhosis

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World Journal of Hepatology 2021年第12期13卷 2071-2080页

作者： Jarosław Jerzy Sak Andrzej Prystupa PawełKiciński Dorota Luchowska-Kocot Ewa Kurys-Denis Hanna Bis-Wencel Chair and Department of Humanities and Social Medicine Medical University of LublinLublin 20-093Poland Department of Internal Medicine Medical University of LublinLublin 20-081Poland Department of Experimental Hematooncology Medical University of LublinLublin 20-080Poland Department of Medical Chemistry Medical University of LublinLublin 20-093Poland The Second Department of Radiology Medical University of LublinLublin 20-081Poland Department of Microbiology and Reproductive Biology University of Life Sciences in LublinLublin 20-950Poland

BACKGROUND The importance of early diagnosis of alcoholic liver disease underscores the need to seek better and especially non-invasive diagnostic *** cellderived chemotaxin-2(LECT2)has been widely studied to determine its usefulness in monitoring the course of non-alcoholic fatty liver disease but not for alcoholic liver cirrhosis(ALC).AIM To determine the concentration of LECT2 in the blood serum of patients in relation to progressive stages of ALC,its relation to fibroblast growth factor 1(FGF-1)and FGF-21,and to examine the possible wider use of LECT2 in diagnosing *** A retrospective case-control study was conducted with 69 ALC cases and 17 controls with no *** were recruited from the region of Lublin(eastern Poland).Liver cirrhosis was diagnosed based on clinical features,history of heavy alcohol consumption,laboratory tests,and abdominal *** degree of ALC was evaluated according to Pugh-Child criteria(the Pugh-Child score).Blood was drawn and,after centrifugation,serum was collected for ***2,FGF-1,and FGF-21 were determined using enzyme-linked immunosorbent assay *** The LECT2 Levels in the control group were 18.99±5.36 ng/*** the study groups,they declined with the progression of cirrhosis to 11.06±6.47 ng/mL in one group and to 8.06±5.74 ng/mL in the other(P21 Levels were 44.27±64.19 pg/mL in the first test group,45.4±51.69 pg/mL in the second(P=0.008),and 13.52±7.51 pg/mL in the control *** difference between the control group and the second test group was statistically significant(P=0.007).CONCLUSION We suggest that LECT2 may be a non-invasive diagnostic factor for alcoholinduced liver *** usefulness of LECT2 for non-invasive monitoring of alcohol-induced liver cirrhosis was indirectly confirmed b

关键词： Leukocyte cell-derived chemotaxin-2 fibroblast growth factor 21 fibroblast growth factor 1 Alcoholic liver cirrhosis Pugh-Child score

Expression of fibroblast growth factor 21 in Escherichia coli Induced by Lactose

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Agricultural Biotechnology 2012年第5期1卷 43-47页

作者： Huiyan WANG Lei LIU Binbin YIN Lei WANG Lei ZHANG Yong JIANG Jianhui CAI Jilin Medical College

[ Objective] This study aimed to investigate the expression of recombinant protein of fibroblast growth factor 21 （ FGF21 ） in Escherichia coli induced by lactose and explore the possibility of engineering production. [ Method ] The effects of lactose concentration, induction duration, induction starting time, and induc- tion temperature on expression of the recombinant product were compared, and the optimal condition for lactose induction was determined with IPTG induction as a control. [ Result] As an induction agent, lactose plays an ideal rele in the production of recombinant FGF21. In addition, the expression level of lactose induction product is consistent with that of IPTG induction product. Induction in a 250 rrd flask containing 50 ml of medium at A600 0.8 - 1.0 using 0.5 g/L lactose at 35 ℃ for 6 h are the optimal condition. [ Conclusion] Lactose can induce the expression of FGF21 gene and achieve ideal results. This study provides experimental basis and reference for the industrial production of FGF21.

关键词： fibroblast growth factor 21 Lactose induction Escherichia coli

FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy fibroblast growth factor 21 Liver diseases mTOR Stress

NASH Drug Development:Seeing the Light at the End of the Tunnel?

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Journal of Clinical and Translational Hepatology 2023年第6期11卷 1397-1403页

作者： Yong Q.Chen Wuxi School of Medicine Jiangnan University Medical CenterWuxiJiangsuChina

Nonalcoholic steatohepatitis(NASH)is a chronic liver disease affecting a large population *** clinically approved drugs are *** this minireview,we discuss the heterogeneous nature of NASH and lack of consensus in outcome measures among clinical *** summarize NASH therapeutic targets and candidate *** compare the efficacy of 33 published clinical trials that evaluated noninvasive biomarkers and liver ***,phase Ⅱ trial results of fibroblast growth factor 21(FGF21)and phase Ⅲ trial results of resmetirom and pioglitazone are encouraging.

关键词： Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis fibroblast growth factor 21