Monoclonal antibody targeting of fibroblast growth factor receptor 1c ameliorates obesity and glucose intolerance via central mechanisms

PLoS ONE

Volumn 9, Issue 11, 2014, Pages

  Lelliott, Christopher J ^a,e   Ahnmark, Andrea ^a   Admyre, Therese ^a   Ahlstedt, Ingela ^a   Irving, Lorraine ^b   Keyes, Feenagh ^b   Patterson, Laurel ^c   Mumphrey, Michael B ^c   Bjursell, Mikael ^a   Gorman, Tracy ^d   Bohlooly Y, Mohammad ^a   Buchanan, Andrew ^b   Harrison, Paula ^b   Vaughan, Tristan ^b   Berthoud, Hans Rudolf ^c   Lindén, Daniel ^a  

^a ASTRAZENECA R AND D   (Sweden)

^b MEDIMMUNE   (United States)

^c PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^d ASTRAZENECA   (United Kingdom)

^e WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

FIBROBLAST GROWTH FACTOR RECEPTOR 1; FIBROBLAST GROWTH FACTOR RECEPTOR 1C; GLUCOSE; LEPTIN; LEPTIN RECEPTOR; MELANIN CONCENTRATING HORMONE RECEPTOR 1; MELANOCORTIN 4 RECEPTOR; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY R1C; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 3; OREXIN; S6 KINASE; UNCLASSIFIED DRUG; FGFR1 PROTEIN, HUMAN; MC4R PROTEIN, MOUSE; MCH1R PROTEIN, MOUSE; MITOGEN ACTIVATED PROTEIN KINASE; SERUM RESPONSE FACTOR; SOMATOSTATIN RECEPTOR;

AGRP GENE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARCUATE NUCLEUS; ARTICLE; BODY FAT; CART GENE; CONTROLLED STUDY; CRH GENE; DRUG ACCUMULATION; DRUG MECHANISM; DRUG SYNTHESIS; DRUG TARGETING; EARLY RESPONSE GENE; ENERGY EXPENDITURE; ENZYME ACTIVATION; FEEDING BEHAVIOR; FEMALE; FOOD INTAKE; GENE; GENE EXPRESSION; GENE LOCATION; GLUCOSE INTOLERANCE; GLYCEMIC CONTROL; HORMONE DEFICIENCY; HYPOTHALAMUS; MALE; MCH GENE; MELANIN CONCENTRATING HORMONE RECEPTOR 1 GENE; MELANOCORTIN 4 RECEPTOR GENE; MONOCYTE CHEMOTACTIC PROTEIN 1 GENE; MONOCYTE CHEMOTACTIC PROTEIN 3 GENE; MOUSE; MOUSE MUTANT; NONHUMAN; NPY GENE; OBESITY; ONCOGENE C FOS; OREXIN GENE; POMC GENE; SINGLE DRUG DOSE; WEIGHT REDUCTION; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; CIRCUMVENTRICULAR ORGAN; DEFICIENCY; DRUG EFFECTS; EATING; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GENETICS; HUMAN; KNOCKOUT MOUSE; METABOLISM; PATHOPHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; ANTIBODIES, MONOCLONAL; ARCUATE NUCLEUS OF HYPOTHALAMUS; CHEMOKINE CCL2; CHEMOKINE CCL7; CIRCUMVENTRICULAR ORGANS; EATING; ENERGY METABOLISM; FEMALE; GENE EXPRESSION REGULATION; GLUCOSE INTOLERANCE; HUMANS; HYPOTHALAMUS; LEPTIN; MICE; MICE, KNOCKOUT; MICE, OBESE; MITOGEN-ACTIVATED PROTEIN KINASES; OBESITY; RECEPTOR, FIBROBLAST GROWTH FACTOR, TYPE 1; RECEPTOR, MELANOCORTIN, TYPE 4; RECEPTORS, SOMATOSTATIN; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; SERUM RESPONSE FACTOR; SIGNAL TRANSDUCTION;

EID: 84913580271     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0112109     Document Type: Article

References (43)

1. Jiao H, Arner P, Dickson SL, Vidal H, Mejhert N, et al. (2011) Genetic association and gene expression analysis identify FGFR1 as a new susceptibility gene for human obesity. J Clin Endocrinol Metab 96: E962-6.
2. Beenken A, Mohammadi M (2009) The FGF family: Biology, pathophysiology and therapy. Nat Rev Drug Discov 8: 235-53.
3. Itoh N, Ornitz DM (2011) Fibroblast growth factors: From molecular evolution to roles in development, metabolism and disease. J Biochem 149: 121-30.
4. Sun HD, Malabunga M, Tonra JR, DiRenzo R, Carrick FE, et al. (2007) Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys. Am J Physiol Endocrinol Metab 292: E964-76.
5. Wu AL, Kolumam G, Stawicki S, Chen Y, Li J, et al. (2011) Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1. Sci Transl Med 3: 113ra126.
6. Dobson CL, Main S, Newton P, Chodorge M, Cadwallader K, et al. (2009) Human monomeric antibody fragments to TRAIL-R1 and TRAIL-R2 that display potent in vitro agonism. MAbs 1: 552-62.
7. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, et al. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88: 131-41.
8. Astrand A, Bohlooly YM, Larsdotter S, Mahlapuu M, Andersen H, et al. (2004) Mice lacking melaninconcentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity. Am J Physiol Regul Integr Comp Physiol 287: R749-58.
9. Gerdin AK, Surve VV, Jonsson M, Bjursell M, Bjorkman M, et al. (2006) Phenotypic screening of hepatocyte nuclear factor (HNF) 4-gamma receptor knockout mice. Biochem Biophys Res Commun 349: 825-32.
10. Sun G, Tarasov AI, McGinty J, McDonald A, da Silva Xavier G, et al. (2010) Ablation of AMPactivated protein kinase alpha1 and alpha2 from mouse pancreatic beta cells and RIP2.cre neurons suppresses insulin release in vivo. Diabetologia 53: 924-36.
11. Grossberg AJ, Scarlett JM, Marks DL (2010) Hypothalamic mechanisms in cachexia. Physiol Behav 100: 478-89.
12. Blouet C, Ono H, Schwartz GJ (2008) Mediobasal hypothalamic p70 S6 kinase 1 modulates the control of energy homeostasis. Cell Metab 8: 459-67.
13. Potes CS, Boyle CN, Wookey PJ, Riediger T, Lutz TA (2012) Involvement of the extracellular signalregulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect. Am J Physiol Regul Integr Comp Physiol 302: R340-51.
14. Rahmouni K, Sigmund CD, Haynes WG, Mark AL (2009) Hypothalamic ERK mediates the anorectic and thermogenic sympathetic effects of leptin. Diabetes 58: 536-42.
15. Sutton GM, Patterson LM, Berthoud HR (2004) Extracellular signal-regulated kinase 1/2 signaling pathway in solitary nucleus mediates cholecystokinin-induced suppression of food intake in rats. J Neurosci 24: 10240-7.
16. Romero-Fernandez W, Borroto-Escuela DO, Tarakanov AO, Mudo G, Narvaez M, et al. (2011) Agonist-induced formation of FGFR1 homodimers and signaling differ among members of the FGF family. Biochem Biophys Res Commun 409: 764-768.
17. Foltz IN, Hu S, King C, Wu X, Yang C, et al. (2012) Treating diabetes and obesity with an FGF21-mimetic antibody activating the betaKlotho/FGFR1c receptor complex. Sci Transl Med 4: 162ra153.
18. Gonzalez AM, Berry M, Maher PA, Logan A, Baird A (1995) A comprehensive analysis of the distribution of FGF-2 and FGFR1 in the rat brain. Brain Res 701: 201-26.
19. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404: 661-71.
20. Thaler JP, Choi SJ, Schwartz MW, Wisse BE (2010) Hypothalamic inflammation and energy homeostasis: Resolving the paradox. Front Neuroendocrinol 31: 79-84.
21. De Souza CT, Araujo EP, Bordin S, Ashimine R, Zollner RL, et al. (2005) Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus. Endocrinology 146: 4192-9.
22. Kleinridders A, Schenten D, Konner AC, Belgardt BF, Mauer J, et al. (2009) MyD88 signaling in the CNS is required for development of fatty acid-induced leptin resistance and diet-induced obesity. Cell Metab 10: 249-59.
23. Milanski M, Degasperi G, Coope A, Morari J, Denis R, et al. (2009) Saturated fatty acids produce an inflammatory response predominantly through the activation of TLR4 signaling in hypothalamus: Implications for the pathogenesis of obesity. J Neurosci 29: 359-70.
24. Posey KA, Clegg DJ, Printz RL, Byun J, Morton GJ, et al. (2009) Hypothalamic proinflammatory lipid accumulation, inflammation, and insulin resistance in rats fed a high-fat diet. Am J Physiol Endocrinol Metab 296: E1003-12.
25. Zhang X, Zhang G, Zhang H, Karin M, Bai H, et al. (2008) Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 135: 61-73.
26. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, et al. (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122: 153-62.
27. Gayle D, Ilyin SE, Flynn MC, Plata-Salaman CR (1998) Lipopolysaccharide (LPS)- and muramyl dipeptide (MDP)-induced anorexia during refeeding following acute fasting: Characterization of brain cytokine and neuropeptide systems mRNAs. Brain Res 795: 77-86.
28. th ventricle causes anorexia that is blocked by agouti-related peptide and that coincides with activation of tyrosine-hydroxylase neurons in the nucleus of the solitary tract. Peptides 30: 210-8.
29. Plata-Salaman CR, Borkoski JP (1994) Chemokines/intercrines and central regulation of feeding. Am J Physiol 266: R1711-5.
30. Banisadr G, Gosselin RD, Mechighel P, Kitabgi P, Rostene W, et al. (2005) Highly regionalized neuronal expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) in rat brain: Evidence for its colocalization with neurotransmitters and neuropeptides. J Comp Neurol 489: 275-92.
31. Banisadr G, Queraud-Lesaux F, Boutterin MC, Pelaprat D, Zalc B, et al. (2002) Distribution, cellular localization and functional role of CCR2 chemokine receptors in adult rat brain. J Neurochem 81: 257-69.
32. Shirazi R, Palsdottir V, Collander J, Anesten F, Vogel H, et al. (2013) Glucagon-like peptide 1 receptor induced suppression of food intake, and body weight is mediated by central IL-1 and IL-6. Proc Natl Acad Sci U S A 110: 16199-16204.
33. Hanai K, Oomura Y, Kai Y, Nishikawa K, Shimizu N, et al. (1989) Central action of acidic fibroblast growth factor in feeding regulation. Am J Physiol 256: R217-23.
34. Hotta M, Kuriyama H, Arai K, Takano K, Shibasaki T (2001) Fibroblast growth factor inhibits locomotor activity as well as feeding behavior of rats. Eur J Pharmacol 416: 101-6.
35. Oomura Y, Sasaki K, Suzuki K, Muto T, Li AJ, et al. (1992) A new brain glucosensor and its physiological significance. Am J Clin Nutr 55: 278S-282S.
36. Li AJ, Oomura Y, Hori T, Aou S, Sasaki K, et al. (1996) Fibroblast growth factor receptor-1 in the lateral hypothalamic area regulates food intake. Exp Neurol 137: 318-23.
37. Garcia-Maya M, Anderson AA, Kendal CE, Kenny AV, Edwards-Ingram LC, et al. (2006) Ligand concentration is a driver of divergent signaling and pleiotropic cellular responses to FGF. J Cell Physiol 206: 386-93.
38. Fry M, Hoyda TD, Ferguson AV (2007) Making sense of it: Roles of the sensory circumventricular organs in feeding and regulation of energy homeostasis. Exp Biol Med (Maywood) 232: 14-26.
39. Smith PM, Chambers AP, Price CJ, Ho W, Hopf C, et al. (2009) The subfornical organ: A central nervous system site for actions of circulating leptin. Am J Physiol Regul Integr Comp Physiol 296: R512-20.
40. Smith PM, Rozanski G, Ferguson AV (2010) Acute electrical stimulation of the subfornical organ induces feeding in satiated rats. Physiol Behav 99: 534-7.
41. Robins SC, Stewart I, McNay DE, Taylor V, Giachino C, et al. (2013) Alpha-tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors. Nat Commun 4: 2049.
42. Balland E, Dam J, Langlet F, Caron E, Steculorum S, et al. (2014) Hypothalamic tanycytes are an ERK-gated conduit for leptin into the brain. Cell Metab 19: 293-301.
43. Hart AW, Baeza N, Apelqvist A, Edlund H (2000) Attenuation of FGF signalling in mouse beta-cells leads to diabetes. Nature 408: 864-8.