FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Bernardo, Barbara ^a   Lu, Min ^b   Bandyopadhyay, Gautam ^a   Li, Pingping ^a   Zhou, Yingjiang ^b   Huang, Jie ^b   Levin, Nancy ^b   Tomas, Eva M ^a   Calle, Roberto A ^a   Erion, Derek M ^a   Rolph, Timothy P ^a   Brenner, Martin ^a   Talukdar, Saswata ^a  

^a PFIZER INC   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FATTY ACID; FIBROBLAST GROWTH FACTOR; FIBROBLAST GROWTH FACTOR 21; GLUCOSE; MONOCLONAL ANTIBODY; PF-05231023;

ANIMAL; BROWN ADIPOSE TISSUE; DISEASE MODEL; DRUG EFFECTS; HOMEOSTASIS; INSULIN RESISTANCE; LIVER; METABOLISM; MOUSE; OBESITY; RAT; ZUCKER RAT;

ADIPOSE TISSUE, BROWN; ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; DISEASE MODELS, ANIMAL; FATTY ACIDS; FIBROBLAST GROWTH FACTORS; GLUCOSE; HOMEOSTASIS; INSULIN RESISTANCE; LIVER; MICE; OBESITY; RATS; RATS, ZUCKER;

EID: 84936966693     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep11382     Document Type: Article

References (40)

1. Kharitonenkov, A. et al. FGF-21 as a novel metabolic regulator. The Journal of clinical investigation 115, 1627-1635, 10.1172/ JCI23606 (2005)
2. Inagaki, T. et al. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell metabolism 5, 415-425, 10.1016/j.cmet.2007.05.003 (2007)
3. Lee, D. V. et al. Fibroblast Growth Factor 21 Improves Insulin Sensitivity and Synergizes with Insulin in Human Adipose Stem Cell-Derived (hASC) Adipocytes. PloS one 9, e111767, 10.1371/journal.pone.0111767 (2014)
4. Xu, J. et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58, 250-259, 10.2337/db08-0392 (2009)
5. Kharitonenkov, A. et al. Rational design of a fibroblast growth factor 21-based clinical candidate, LY2405319. PloS one 8, e58575, 10.1371/journal.pone.0058575 (2013)
6. Coskun, T. et al. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149, 6018-6027, 10.1210/en.2008-0816 (2008)
7. Gaich, G. et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell metabolism 18, 333-340, 10.1016/j.cmet.2013.08.005 (2013)
8. Ding, X. et al. betaKlotho is required for fibroblast growth factor 21 effects on growth and metabolism. Cell metabolism 16, 387-393, 10.1016/j.cmet.2012.08.002 (2012)
9. Foltz, I. N. et al. Treating diabetes and obesity with an FGF21-mimetic antibody activating the betaKlotho/FGFR1c receptor complex. Science translational medicine 4, 162ra153, 10.1126/scitranslmed.3004690 (2012)
10. Adams, A. C. et al. The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue. Molecular metabolism 2, 31-37, 10.1016/j.molmet.2012.08.007 (2012)
11. Smith, R. et al. FGF21 can be mimicked in vitro and in vivo by a novel anti-FGFR1c/beta-Klotho bispecific protein. PloS one 8, e61432, 10.1371/journal.pone.0061432 (2013)
12. Fon Tacer, K. et al. Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Molecular endocrinology 24, 2050-2064, 10.1210/me.2010-0142 (2010)
13. Yang, C. et al. Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB. PloS one 7, e33870, 10.1371/journal.pone.0033870 (2012)
14. Adams, A. C. et al. Fundamentals of FGF19 &FGF21 action in vitro and in vivo. PloS one 7, e38438, 10.1371/journal. pone.0038438 (2012)
15. Holland, W. L. et al. An FGF21-Adiponectin-ceramide axis controls energy expenditure and insulin action in mice. Cell metabolism 17, 790-797, 10.1016/j.cmet.2013.03.019 (2013)
16. Owen, B. M. et al. FGF21 Acts Centrally to Induce Sympathetic Nerve Activity, Energy Expenditure, and Weight Loss. Cell metabolism, 10.1016/j.cmet.2014.07.012 (2014)
17. Fisher, F. M. et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes &development 26, 271-281, 10.1101/gad.177857.111 (2012)
18. Huang, J. et al. Development of a Novel Long-Acting Antidiabetic FGF21 Mimetic by Targeted Conjugation to a Scaffold Antibody. The Journal of pharmacology and experimental therapeutics 346, 270-280, 10.1124/jpet.113.204420 (2013)
19. Wu, A. L. et al. FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways. PloS one 6, e17868, 10.1371/journal.pone.0017868 (2011)
20. Kim, H. W. et al. Fibroblast growth factor 21 improves insulin resistance and ameliorates renal injury in db/db mice. Endocrinology 154, 3366-3376, 10.1210/en.2012-2276 (2013)
21. Camporez, J. P. et al. Cellular mechanisms by which FGF21 improves insulin sensitivity in male mice. Endocrinology 154, 3099-3109, 10.1210/en.2013-1191 (2013)
22. Weng, Y. et al. Pharmacokinetics (PK), Pharmacodynamics (PD) and Integrated PK/PD Modeling of a Novel Long Acting FGF21 Clinical Candidate PF-05231023 in Diet-Induced Obese and Leptin-Deficient Obese Mice. PloS one 10, e0119104, 10.1371/ journal.pone.0119104 (2015)
23. Chartoumpekis, D. V. et al. Brown adipose tissue responds to cold and adrenergic stimulation by induction of FGF21. Molecular medicine 17, 736-740, 10.2119/molmed.2011.00075 (2011)
24. Hondares, E. et al. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. The Journal of biological chemistry 286, 12983-12990, 10.1074/jbc.M110.215889 (2011)
25. Gimeno, R. E. &Moller, D. E. FGF21-based pharmacotherapy-potential utility for metabolic disorders. Trends in endocrinology and metabolism: TEM, 10.1016/j.tem.2014.03.001 (2014)
26. Adams, A. C. et al. LY2405319, an Engineered FGF21 Variant, Improves the Metabolic Status of Diabetic Monkeys. PloS one 8, e65763, 10.1371/journal.pone.0065763 (2013)
27. Augstein, P. &Salzsieder, E. Morphology of pancreatic islets: A time course of pre-diabetes in Zucker fatty rats. Methods in molecular biology 560, 159-189, 10.1007/978-1-59745-448-3-12 (2009)
28. Cyphert, H. A. et al. Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21. The Journal of biological chemistry 287, 25123-25138, 10.1074/jbc.M112.375907 (2012)
29. Gallego-Escuredo, J. M. et al. Opposite alterations in FGF21 and FGF19 levels and disturbed expression of the receptor machinery for endocrine FGFs in obese patients. International journal of obesity 39, 121-129, 10.1038/ijo.2014.76 (2015)
30. Mu, J. et al. Anti-diabetic efficacy and impact on amino acid metabolism of GRA1, a novel small-molecule glucagon receptor antagonist. PloS one 7, e49572, 10.1371/journal.pone.0049572 (2012)
31. Nedergaard, J. &Cannon, B. The browning of white adipose tissue: some burning issues. Cell metabolism 20, 396-407, 10.1016/j.cmet.2014.07.005 (2014)
32. Stanford, K. I. et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. The Journal of clinical investigation 123, 215-223, 10.1172/JCI62308 (2013)
33. Isler, D., Hill, H. P. &Meier, M. K. Glucose metabolism in isolated brown adipocytes under beta-Adrenergic stimulation. Quantitative contribution of glucose to total thermogenesis. The Biochemical journal 245, 789-793 (1987)
34. Cinti, S. Between brown and white: novel aspects of adipocyte differentiation. Annals of medicine 43, 104-115, 10.3109/078 53890.2010.535557 (2011)
35. Cannon, B. &Nedergaard, J. Brown adipose tissue: function and physiological significance. Physiological reviews 84, 277-359, 10.1152/physrev.00015.2003 (2004)
36. Veniant, M. M. et al. FGF21 promotes metabolic homeostasis via white adipose and leptin in mice. PloS one 7, e40164, 10.1371/journal.pone.0040164 (2012)
37. Lin, Z. et al. Adiponectin mediates the metabolic effects of FGF21 on glucose homeostasis and insulin sensitivity in mice. Cell metabolism 17, 779-789, 10.1016/j.cmet.2013.04.005 (2013)
38. Osborn, O. et al. G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. The Journal of clinical investigation 122, 2444-2453, 10.1172/JCI61953 (2012)
39. Lu, M. et al. Neuronal Sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues. The Journal of biological chemistry 288, 10722-10735, 10.1074/jbc.M112.443606 (2013)
40. Talukdar, S. et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nature medicine 18, 1407-1412, 10.1038/nm.2885 (2012)