المؤلفون: Krister Bokvist, Yanyun Chen, Julie S. Moyers, Mezo Adam Robert, Melissa K. Thomas, Tamer Coskun, Min Song, William C. Roell, Valenzuela Francisco Alcides, Hongchang Qu

المصدر: Diabetes. 70

مصطلحات موضوعية: Agonist, medicine.medical_specialty, FGF21, Peptide analog, medicine.drug_class, business.industry, Endocrinology, Diabetes and Metabolism, Semaglutide, Glucagon, Oxyntomodulin, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, Internal Medicine, medicine, Receptor, business, Glucagon-like peptide 1 receptor

الوصف: LY3305677 (LY) is a synthetic peptide analog of mammalian oxyntomodulin with a fatty acyl side chain to extend time action. LY functions are mediated by binding and activation of both glucagon (GcgR) and glucagon-like peptide-1 (GLP-1R) receptors. LY is bound with potent binding affinity (Ki) to human and mouse GcgR (Ki: 17.7 nM and 15.9 nM, respectively) and GLP-1R (Ki: 28.6 nM and 25.1 nM, respectively). LY dose-dependently stimulated insulin secretion in mouse pancreatic islets (EC50: 5.2 nM) and in mice. In oral glucose tolerance tests of diet-induced obese (DIO) and streptozotocin-induced diabetic mice, a single subcutaneous (SC) dose of LY significantly reduced glucose area under the curve by up to 65%. SC injections of LY to DIO mice dose-dependently reduced serum triglycerides and PCSK9 (proprotein convertase subtilisin/kexin type 9) levels and dose-dependently increased FGF21 (fibroblast growth factor 21) levels. In DIO mice treated over 18 days, LY 30 nmol/kg reduced body weight to a greater extent (33%) than semaglutide 60 nmol/kg (12%), and decreased food intake by 50% compared to vehicle. At Day 18, LY 30 nmol/kg group lost 33% of initial bodyweight, which was primarily due to 70% reduced fat mass. LY reduced liver triglycerides by greater than 70% and increased serum ketones by more than 3-fold compared to vehicle, suggestive of increased fatty acid oxidation. LY decreased body weight in both GcgR knock-out (KO) and GLP-1R KO mice, indicating that activation of both receptors contributed to greater weight loss. To assess potential changes in energy expenditure, DIO mice were treated chronically with SC LY (15 nmol/kg), semaglutide (60 nmol/kg), or vehicle. LY, but not semaglutide, increased energy expenditure as compared with vehicle. These preclinical studies indicate that novel dual GcgR and GLP-1R agonist LY may have potential to enhance metabolic health by improving dyslipidemia, hyperglycemia, or obesity. Disclosure Y. Chen: None. H. Qu: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. A. Mezo: None. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. Song: None. W. C. Roell: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. B. Bokvist: Employee; Self; Eli Lilly and Company, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Self; Johnson & Johnson, Sanofi-Aventis Deutschland GmbH, Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. J. S. Moyers: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. M. K. Thomas: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. F. Valenzuela: None. Funding Eli Lilly and Company

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::fa273a6e8b63606b2790d9ac363a0bf1Test
https://doi.org/10.2337/db21-682-pTest

المؤلفون: Audrey Ayer, Soazig Le Lay, Cédric Le May, Tamer Coskun, Xavier Prieur, Jocelyne Magré, L. Dollet, Quentin Venara, Ruth E. Gimeno, Bertrand Cariou, Clara Levrel, Andrew C. Adams

المساهمون: unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stress Oxydant et Pathologies Métaboliques (SOPAM), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)

المصدر: Diabetes
Diabetes, 2016, Equipe 5, 65 (11), pp.3410--3417. ⟨10.2337/db16-0327⟩
Diabetes, American Diabetes Association, 2016, 65 (11), pp.3410-3417. ⟨10.2337/db16-0327⟩

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, FGF21, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Adipocytes, White, Blotting, Western, White adipose tissue, Biology, Seipin, Mice, 03 medical and health sciences, chemistry.chemical_compound, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3T3-L1 Cells, GTP-Binding Protein gamma Subunits, Adipocyte, Internal medicine, Internal Medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Homeostasis, Adiponectin secretion, RNA, Messenger, ComputingMilieux_MISCELLANEOUS, Mice, Knockout, Gene knockdown, Adiponectin, Adipose tissue loss, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Heterotrimeric GTP-Binding Proteins, 3. Good health, Fibroblast Growth Factors, 030104 developmental biology, Endocrinology, Adipose Tissue, chemistry

الوصف: International audience; Fibroblast growth factor 21 (FGF21) was shown to improve metabolic homeostasis, at least partly by controlling white adipocyte profile and adiponectin secretion. Here, we studied its effect on adipocyte dysfunction in the context of Berardinelli-Seip congenital lipodystrophy (BSCL) linked to seipin deficiency. Bscl2(-/-) mice displayed a progressive adipose tissue loss with aging as evidenced by the altered profile of residual fat pads and the decrease in adiponectin plasma levels in 12- vs. 4-week-old animals. Aiming to prevent this impairment, we treated 6-week-old Bscl2(-/-) mice with an FGF21 analog (LY2405319) for a period of 28 days. FGF21 treatment increased adiponectin plasma levels and normalized insulin sensitivity in Bscl2(-/-) mice by improving the white adipose tissue gene expression pattern. To further decipher the molecular pathways altered by seipin deficiency in mature adipocytes, we developed a unique inducible seipin knockdown cell line (SKD). SKD showed chronic activation of the p38 MAPK pathway associated with apoptotic cell death. Interestingly, FGF21 treatment exerted an antistress effect on SKD cells, reducing p38 MAPK phosphorylation and limiting mature adipocyte loss. Our data demonstrate that FGF21 treatment improves the metabolic profile of Bscl2(-/-) lipodystrophic mice, partly by improving mature adipocyte maintenance through suppression of cellular stress via inhibition of p38 MAPK activity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc7641d61bcbaab81e84bf97c38a83bbTest
https://hal.archives-ouvertes.fr/hal-01831750Test

المؤلفون: Christine C. Cheng, Tamer Coskun, Alexei Kharitonenkov, Libbey S. O′Farrell, Susan L. DuBois, Andrew C. Adams

المصدر: Molecular Metabolism. 2:205-214

مصطلحات موضوعية: medicine.medical_specialty, FGF21, Side effect, Adiponectin, business.industry, Regulator, Adipose tissue, Cell Biology, Metabolism, Pharmacology, Endocrinology, Internal medicine, medicine, Original Article, Cytokine secretion, Rosiglitazone, business, Molecular Biology, medicine.drug

الوصف: Fibroblast growth factor 21 is an emerging metabolic regulator that was recently proposed to be a fed-state inducible factor in adipose tissue. As mice lacking FGF21 were refractory to treatment with rosiglitazone, FGF21 was suggested to underlie PPARγ-driven pharmacology and side effect profile (Dutchak et al., 2012 [12]). To evaluate FGF21/PPARγ cross-talk we conducted experiments in control and FGF21 null animals and found that rosiglitazone was equally efficacious in both strains. Specifically, diverse endpoints ranging from enhanced glycemic control, improved lipid homeostasis and side effects such as adipose accumulation were evident in both genotypes. Furthermore, the transcriptional signature and cytokine secretion profile of rosiglitazone action were maintained in our FGF21KO animals. Finally, we found that FGF21 in adipose was expressed at comparable levels in fasted and fed states. Thus, our data present a new viewpoint on the FGF21/PPARγ interplay whereby FGF21 is not necessary for the metabolic events downstream of PPARγ.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f8d1d308dad531b94280ca28147ac658Test
https://doi.org/10.1016/j.molmet.2013.05.005Test

المؤلفون: Andrew C. Adams, Yongde Luo, Christine C. Cheng, Chaofeng Yang, Tamer Coskun, Ruth E. Gimeno, Alexei Kharitonenkov

المصدر: Molecular Metabolism. 2(1):31-37

مصطلحات موضوعية: medicine.medical_specialty, FGF21, Insulin, medicine.medical_treatment, Brief Report, Adipokine, Adipose tissue, Cell Biology, White adipose tissue, Biology, Thermogenin, Endocrinology, medicine.anatomical_structure, Internal medicine, Brown adipose tissue, medicine, Molecular Biology, Diet-induced obese

الوصف: FGF21 is a multifunctional metabolic regulator. The co-factor βKlotho (KLB) allows FGF21 to signal via FGF receptors. Given the widespread nature of FGFR expression and KLB presence in several organs, it remains unclear which tissue/FGFR isoform determine FGF21 action. Here we show that deletion of FGFR1 in fat (FR1KO) leads to a complete ablation of FGF21 stimulated transcriptional activity in this tissue. Furthermore, FR1KO mice showed no FGF21-mediated lowering of plasma glucose, insulin and triglycerides, altered serum levels of adipokines, no increase in energy expenditure, but preserved reductions in serum/liver FFAs as compared to wild type mice. Of importance, the anti-glycaemic actions of FGF19 were fully evident in FR1KO mice implying that FGF19 functions in a FGFR1/adipose independent manner. Taken together, our findings reveal the existence of an adipose FGFR1 driven axis of cross-tissue communication which defines several aspects of FGF21 biology and delineates mechanistic distinctions between FGF21 and FGF19.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df05084bf5e907044cf2de4b6e581430Test

المؤلفون: Alexei Kharitonenkov, Paul J. Emmerson, Andrew C. Adams, Kostas Tsintzas, Francis J. P. Ebling, Ricardo J. Samms, Tamer Coskun, Maxine J Fowler, Scott Cooper

مصطلحات موضوعية: Male, medicine.medical_specialty, FGF21, Phodopus, media_common.quotation_subject, Photoperiod, Hamster, White adipose tissue, Biology, Behavioral Neuroscience, Eating, Endocrinology, Internal medicine, Cricetinae, Brown adipose tissue, Ketogenesis, medicine, Endocrine system, Animals, media_common, Endocrine and Autonomic Systems, Catabolism, Appetite, Fibroblast Growth Factors, medicine.anatomical_structure, Appetite, Metabolic rate, Energy expenditure, Photoperiod, Energy Metabolism

الوصف: This article is part of a Special Issue "Energy Balance". FGF21 is an endocrine member of the fibroblast growth factor superfamily that has been shown to play an important role in the physiological response to nutrient deprivation. Food restriction enhances hepatic FGF21 production, which serves to engage an integrated response to energy deficit. Specifically, elevated FGF21 levels lead to reduced gluconeogenesis and increased hepatic ketogenesis. However, circulating FGF21 concentrations also paradoxically rise in states of metabolic dysfunction such as obesity. Furthermore, multiple peripheral tissues also produce FGF21 in addition to the liver, raising questions as to its endocrine and paracrine roles in the control of energy metabolism. The objectives of this study were to measure plasma FGF21 concentrations in the Siberian hamster, a rodent which undergoes a seasonal cycle of fattening and body weight gain in the long days (LD) of summer, followed by reduction of appetite and fat catabolism in the short days (SD) of winter. Groups of adult male hamsters were raised in long days, and then exposed to SD for up to 12 weeks. Chronic exposure of LD animals to SD led to a significant increase in circulating FGF21 concentrations. This elevation of circulating FGF21 was preceded by an increase in liver FGF21 protein production evident as early as 4 weeks of exposure to SD. FGF21 protein abundance was also increased significantly in interscapular brown adipose tissue, with a positive correlation between plasma levels of FGF21 and BAT protein abundance throughout the experimental period. Epididymal white adipose tissue and skeletal muscle (gastrocnemius) also produced FGF21, but levels did not change in response to a change in photoperiod. In summary, a natural programmed state of fat catabolism was associated with increased FGF21 production in the liver and BAT, consistent with the view that FGF21 has a role in adapting hamsters to the hypophagic winter state.

وصف الملف: application/pdf; PDF

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::de11d9694c7bc47fc154dc4878c5c32eTest
http://eprints.nottingham.ac.uk/34343Test/

المؤلفون: Ricardo J. Samms, Andrew C. Adams, Ebling Ebling, Emmerson Paul, Alexi Kharitonenkov, Tamer Coskun, Perry Barrett, Kostas Tsintzas, Michelle Murphy

المصدر: The FASEB Journal. 28

مصطلحات موضوعية: medicine.medical_specialty, Animal model, Liver metabolism, Endocrinology, FGF21, Internal medicine, Genetics, medicine, Biology, Whole body, Molecular Biology, Biochemistry, Biotechnology

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::c01b109c6f99829fb8d60425196ea235Test
https://doi.org/10.1096/fasebj.28.1_supplement.1101.7Test

المؤلفون: Bumol Thomas Frank, Christopher C. Frye, John Michael Beals, Tamer Coskun, Alexei Kharitonenkov, Radhakrishnan Rathnachalam, James D. Dunbar, Victor J. Wroblewski, Beth A. Strifler, Shun Li, Christine C. Cheng, Anja Koester, David E. Moller, Radmila Micanovic, Amy M. Ford

المصدر: PLoS ONE
PLoS ONE, Vol 8, Iss 3, p e58575 (2013)

مصطلحات موضوعية: Male, Models, Molecular, Drugs and Devices, FGF21, Drug Research and Development, Non-Clinical Medicine, Protein Conformation, lcsh:Medicine, Gene Expression, Biology, Fibroblast growth factor, Cardiovascular Pharmacology, Pichia, Pichia pastoris, Cell Line, Mice, Endocrinology, In vivo, Animals, Humans, lcsh:Science, Klotho Proteins, chemistry.chemical_classification, Diabetic Endocrinology, Multidisciplinary, Endocrine Physiology, Protein Stability, lcsh:R, Drug Information, Wild type, Temperature, Genetic Variation, Membrane Proteins, 3T3 Cells, Hep G2 Cells, biology.organism_classification, In vitro, Recombinant Proteins, Amino acid, Fibroblast Growth Factors, Biopharmaceutical, chemistry, Biochemistry, Amino Acid Substitution, Metabolic Disorders, Drug Design, Medicine, lcsh:Q, Research Article

الوصف: Fibroblast growth factor 21 is a novel hormonal regulator with the potential to treat a broad variety of metabolic abnormalities, such as type 2 diabetes, obesity, hepatic steatosis, and cardiovascular disease. Human recombinant wild type FGF21 (FGF21) has been shown to ameliorate metabolic disorders in rodents and non-human primates. However, development of FGF21 as a drug is challenging and requires re-engineering of its amino acid sequence to improve protein expression and formulation stability. Here we report the design and characterization of a novel FGF21 variant, LY2405319. To enable the development of a potential drug product with a once-daily dosing profile, in a preserved, multi-use formulation, an additional disulfide bond was introduced in FGF21 through Leu118Cys and Ala134Cys mutations. FGF21 was further optimized by deleting the four N-terminal amino acids, His-Pro-Ile-Pro (HPIP), which was subject to proteolytic cleavage. In addition, to eliminate an O-linked glycosylation site in yeast a Ser167Ala mutation was introduced, thus allowing large-scale, homogenous protein production in Pichia pastoris. Altogether re-engineering of FGF21 led to significant improvements in its biopharmaceutical properties. The impact of these changes was assessed in a panel of in vitro and in vivo assays, which confirmed that biological properties of LY2405319 were essentially identical to FGF21. Specifically, subcutaneous administration of LY2405319 in ob/ob and diet-induced obese (DIO) mice over 7–14 days resulted in a 25–50% lowering of plasma glucose coupled with a 10–30% reduction in body weight. Thus, LY2405319 exhibited all the biopharmaceutical and biological properties required for initiation of a clinical program designed to test the hypothesis that administration of exogenous FGF21 would result in effects on disease-related metabolic parameters in humans.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d743e028a69d60dcee0846768123348dTest
http://europepmc.org/articles/PMC3594191Test

المؤلفون: Perry Barrett, Ricardo J. Samms, Andrew C. Adams, Tamer Coskun, Maxine J Fowler, Francis J. P. Ebling, Alexei Kharitonenkov, Amy Warner, John M. Brameld, Michelle Murphy, Kostas Tsintzas, Matei Bolborea

المصدر: Journal of neuroendocrinology. 25(2)

مصطلحات موضوعية: Male, medicine.medical_specialty, FGF21, Phodopus, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Photoperiod, Hypothalamus, Adipose tissue, Hamster, Gene Expression, Biology, Cellular and Molecular Neuroscience, Eating, Endocrinology, Weight loss, Internal medicine, Cricetinae, medicine, Animals, Homeostasis, Respiratory exchange ratio, media_common, Adiposity, photoperiodism, Endocrine and Autonomic Systems, Body Weight, Appetite, Overweight, Fibroblast Growth Factors, Models, Animal, Seasons, medicine.symptom, Energy Metabolism, Weight gain

الوصف: The present study aimed to investigate the actions of fibroblast growth factor 21 (FGF21) on energy balance in a natural model of relative fatness, the Siberian hamster. Hamsters were studied under long days (LD) to promote weight gain, or short days to induce weight loss, and treated with rhFGF21 (3 mg/kg/day) via s.c. minipumps for 14 days. On days 7–9, detailed assessments of ingestive behaviour, metabolic gas exchange and locomotor activity were made. FGF21 caused substantial (P < 0.0001) weight loss in the fat LD state but not in the lean SD state: at the end of the study, FGF21-treated hamsters in LD lost 18% of body weight compared to vehicle controls, which is comparable to the natural body weight loss observed in SD. Epididymal fat pads, a correlate of total carcass fat content, were reduced by 19% in FGF21 treated hamsters in LD, whereas no difference was found in SD. Body weight loss in LD was associated with a reduction in food intake (P < 0.001) and a decreased respiratory exchange ratio (P < 0.001), indicating increased fat oxidation. Treatment with FGF21 maintained the normal nocturnal increase in oxygen consumption and carbon dioxide production into the early light phase in hamsters in LD, indicating increased energy expenditure, although locomotor activity was unaffected. These data suggest a greater efficacy of FGF21 in hamsters in LD compared to those in SD, which is consistent with both the peripheral and possibly central actions of FGF21 with respect to promoting a lean phenotype. The observed differences in FGF21 sensitivity may relate to day length-induced changes in adipose tissue mass.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdbb73c8b2321d6d62495a3dda11dac0Test
https://pubmed.ncbi.nlm.nih.gov/22958332Test

المؤلفون: Tamer Coskun, Alexei Kharitonenkov, Andrew C. Adams, Christine C. Cheng

المصدر: PLoS ONE, Vol 7, Iss 11, p e49977 (2012)
PLoS ONE

مصطلحات موضوعية: Scaffold protein, Male, medicine.medical_specialty, FGF21, Anatomy and Physiology, Mouse, Adipose Tissue, White, Adipose tissue, lcsh:Medicine, Endocrine System, Biology, Fibroblast growth factor, Mice, Model Organisms, Endocrinology, In vivo, Internal medicine, Integrative Physiology, Brown adipose tissue, medicine, Glucose homeostasis, Animals, lcsh:Science, Klotho Proteins, Regulation of gene expression, Mice, Knockout, Diabetic Endocrinology, Multidisciplinary, lcsh:R, Membrane Proteins, Animal Models, Cell biology, Fibroblast Growth Factors, medicine.anatomical_structure, Gene Expression Regulation, Liver, Medicine, Female, lcsh:Q, Energy Metabolism, Physiological Processes, Research Article

الوصف: FGF21 has gradually become a focal point in metabolic research given its intriguing and complex biology and relevance to drug discovery. Despite the large amount of accumulated data, there remains a dearth of understanding of FGF21 physiology at the molecular/whole organism level. The scaffold protein βklotho (KLB) has previously been demonstrated in vitro to function as a co-factor permitting FGF21 mediated FGF receptor activation. However, the requirement for KLB in the propagation of FGF21 action in living animals has yet to be evaluated. To answer this question, we tested FGF21 in mice with total body ablation of KLB (KLBKO) and found no detectable activity. Firstly, we demonstrate that the disruption of KLB entirely abrogates acute FGF21 signaling in adipose tissue. We go on to show that this signaling defect translates to the absence of FGF21 mediated metabolic improvements in DIO mice. Indeed, KLBKO mice are totally refractory to FGF21-induced normalization of glucose homeostasis, attenuation of dyslipidemia, elevation of energy expenditure and weight loss. The lack of FGF21-driven effects was further substantiated at the transcriptional level with no FGF21 target gene signature detectable in adipose tissue and liver of KLBKO animals. Taken together our data show that KLB is a vital component of the FGF21 in vivo signaling machinery and is critically required for FGF21 action at the whole organism level.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d9fac3e8e74e9bf8c402c05b4298c34Test
http://europepmc.org/articles/PMC3507945?pdf=renderTest

المؤلفون: Tamer Coskun, Holly A. Bina, Charlie C. Hu, Michael Schneider, David E. Moller, James D. Dunbar, Alexei Kharitonenkov, Yanyun Chen

المصدر: Endocrinology. 149(12)

مصطلحات موضوعية: Leptin, Male, medicine.medical_specialty, FGF21, medicine.medical_treatment, Population, Biology, Motor Activity, Mice, Endocrinology, Insulin resistance, Internal medicine, medicine, Animals, Insulin, Obesity, education, Adiposity, education.field_of_study, Fatty liver, Body Weight, medicine.disease, Dietary Fats, Fibroblast Growth Factors, Mice, Inbred C57BL, Lipogenesis, Insulin Resistance, Energy Intake, Energy Metabolism

الوصف: Fibroblast growth factor 21 (FGF21) is a metabolic regulator that provides efficient and durable glycemic and lipid control in various animal models. However, its potential to treat obesity, a major health concern affecting over 30% of the population, has not been fully explored. Here we report that systemic administration of FGF21 for 2 wk in diet-induced obese and ob/ob mice lowered their mean body weight by 20% predominantly via a reduction in adiposity. Although no decrease in total caloric intake or effect on physical activity was observed, FGF21-treated animals exhibited increased energy expenditure, fat utilization, and lipid excretion, reduced hepatosteatosis, and ameliorated glycemia. Transcriptional and blood cytokine profiling studies revealed effects consistent with the ability of FGF21 to ameliorate insulin and leptin resistance, enhance fat oxidation and suppress de novo lipogenesis in liver as well as to activate futile cycling in adipose. Overall, these data suggest that FGF21 exhibits the therapeutic characteristics necessary for an effective treatment of obesity and fatty liver disease and provides novel insights into the metabolic determinants of these activities.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e43d51a4f22a9894a9bb9dd24705cc59Test
https://pubmed.ncbi.nlm.nih.gov/18687777Test