Pharmacologic Effects of FGF21 Are Independent of the “Browning” of White Adipose Tissue

Cell Metabolism

Volumn 21, Issue 5, 2015, Pages 731-738

  Véniant, Murielle M ^a   Sivits, Glenn ^a   Helmering, Joan ^a   Komorowski, Renee ^a   Lee, Jae ^a   Fan, Wei ^a   Moyer, Carolyn ^a   Lloyd, David J ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOBESITY AGENT; FIBROBLAST GROWTH FACTOR 21; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; UNCOUPLING PROTEIN 1; UNCOUPLING PROTEIN 2; UNCOUPLING PROTEIN 3; ANTIDIABETIC AGENT; FIBROBLAST GROWTH FACTOR; GLUCOSE; ION CHANNEL; MITOCHONDRIAL PROTEIN; MITOCHONDRIAL UNCOUPLING PROTEIN;

ADIPOCYTE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIDIABETIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; ENERGY EXPENDITURE; GLUCOSE HOMEOSTASIS; GLYCATION; LEAN BODY WEIGHT; LIPID BLOOD LEVEL; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; TEMPERATURE DEPENDENCE; WEIGHT REDUCTION; WHITE ADIPOSE TISSUE; ADVERSE EFFECTS; ANIMAL; BROWN ADIPOCYTE; BROWN ADIPOSE TISSUE; C57BL MOUSE; DIET; DRUG EFFECTS; ENERGY METABOLISM; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MOUSE MUTANT; PATHOLOGY; PATHOPHYSIOLOGY; THERMOGENESIS;

ADIPOCYTES, BROWN; ADIPOSE TISSUE, BROWN; ADIPOSE TISSUE, WHITE; ANIMALS; ANTI-OBESITY AGENTS; DIET; ENERGY METABOLISM; FIBROBLAST GROWTH FACTORS; GENE EXPRESSION REGULATION; GLUCOSE; HYPOGLYCEMIC AGENTS; ION CHANNELS; MALE; MICE; MICE, INBRED C57BL; MICE, OBESE; MITOCHONDRIAL PROTEINS; OBESITY; THERMOGENESIS;

EID: 84930579383     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2015.04.019     Document Type: Article

References (29)

1. Adams, A.C., Yang, C., Coskun, T., Cheng, C.C., Gimeno, R.E., Luo, Y., Kharitonenkov, A., The breadth of FGF21’s metabolic actions are governed by FGFR1 in adipose tissue. Mol. Metab. 2 (2012), 31–37.
2. Berglund, E.D., Li, C.Y., Bina, H.A., Lynes, S.E., Michael, M.D., Shanafelt, A.B., Kharitonenkov, A., Wasserman, D.H., Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 150 (2009), 4084–4093.
3. Boon, M.R., van den Berg, S.A., Wang, Y., van den Bossche, J., Karkampouna, S., Bauwens, M., De Saint-Hubert, M., van der Horst, G., Vukicevic, S., de Winther, M.P., et al. BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. PLoS ONE, 8, 2013, e74083.
4. Chau, M.D., Gao, J., Yang, Q., Wu, Z., Gromada, J., Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc. Natl. Acad. Sci. USA 107 (2010), 12553–12558.
5. Chechi, K., Carpentier, A.C., Richard, D., Understanding the brown adipocyte as a contributor to energy homeostasis. Trends Endocrinol. Metab. 24 (2013), 408–420.
6. Chechi, K., Nedergaard, J., Richard, D., Brown adipose tissue as an anti-obesity tissue in humans. Obes. Rev. 15 (2014), 92–106.
7. Coskun, T., Bina, H.A., Schneider, M.A., Dunbar, J.D., Hu, C.C., Chen, Y., Moller, D.E., Kharitonenkov, A., Fibroblast growth factor 21 corrects obesity in mice. Endocrinology 149 (2008), 6018–6027.
8. Emanuelli, B., Vienberg, S.G., Smyth, G., Cheng, C., Stanford, K.I., Arumugam, M., Michael, M.D., Adams, A.C., Kharitonenkov, A., Kahn, C.R., Interplay between FGF21 and insulin action in the liver regulates metabolism. J. Clin. Invest. 124 (2014), 515–527.
9. Enerbäck, S., Jacobsson, A., Simpson, E.M., Guerra, C., Yamashita, H., Harper, M.E., Kozak, L.P., Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387 (1997), 90–94.
10. Feldmann, H.M., Golozoubova, V., Cannon, B., Nedergaard, J., UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 9 (2009), 203–209.
11. Fisher, F.M., Kleiner, S., Douris, N., Fox, E.C., Mepani, R.J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J.S., Maratos-Flier, E., Spiegelman, B.M., FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 26 (2012), 271–281.
12. Foltz, I.N., Hu, S., King, C., Wu, X., Yang, C., Wang, W., Weiszmann, J., Stevens, J., Chen, J.S., Nuanmanee, N., et al. Treating diabetes and obesity with an FGF21-mimetic antibody activating the betaKlotho/FGFR1c receptor complex. Sci. Transl. Med., 4, 2012, 162ra153.
13. Giralt, M., Villarroya, F., White, brown, beige/brite: different adipose cells for different functions?. Endocrinology 154 (2013), 2992–3000.
14. Hecht, R., Li, Y.S., Sun, J., Belouski, E., Hall, M., Hager, T., Yie, J., Wang, W., Winters, D., Smith, S., et al. Rationale-based engineering of a potent long-acting FGF21 analog for the treatment of type 2 diabetes. PLoS ONE, 7, 2012, e49345.
15. Hondares, E., Rosell, M., Gonzalez, F.J., Giralt, M., Iglesias, R., Villarroya, F., Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat. Cell Metab. 11 (2010), 206–212.
16. Hondares, E., Iglesias, R., Giralt, A., Gonzalez, F.J., Giralt, M., Mampel, T., Villarroya, F., Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J. Biol. Chem. 286 (2011), 12983–12990.
17. Hondares, E., Gallego-Escuredo, J.M., Flachs, P., Frontini, A., Cereijo, R., Goday, A., Perugini, J., Kopecky, P., Giralt, M., Cinti, S., et al. Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue. Metabolism 63 (2014), 312–317.
18. Ito, S., Kinoshita, S., Shiraishi, N., Nakagawa, S., Sekine, S., Fujimori, T., Nabeshima, Y.I., Molecular cloning and expression analyses of mouse betaklotho, which encodes a novel Klotho family protein. Mech. Dev. 98 (2000), 115–119.
19. Kharitonenkov, A., Shiyanova, T.L., Koester, A., Ford, A.M., Micanovic, R., Galbreath, E.J., Sandusky, G.E., Hammond, L.J., Moyers, J.S., Owens, R.A., et al. FGF-21 as a novel metabolic regulator. J. Clin. Invest. 115 (2005), 1627–1635.
20. Lee, P., Linderman, J.D., Smith, S., Brychta, R.J., Wang, J., Idelson, C., Perron, R.M., Werner, C.D., Phan, G.Q., Kammula, U.S., et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 19 (2014), 302–309.
21. Lee, P., Werner, C.D., Kebebew, E., Celi, F.S., Functional thermogenic beige adipogenesis is inducible in human neck fat. Int. J. Obes. (Lond.) 38 (2014), 170–176.
22. Nedergaard, J., Golozoubova, V., Matthias, A., Asadi, A., Jacobsson, A., Cannon, B., UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim. Biophys. Acta 1504 (2001), 82–106.
23. Potthoff, M.J., Inagaki, T., Satapati, S., Ding, X., He, T., Goetz, R., Mohammadi, M., Finck, B.N., Mangelsdorf, D.J., Kliewer, S.A., Burgess, S.C., FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. Proc. Natl. Acad. Sci. USA 106 (2009), 10853–10858.
24. Sammons, M.F., Price, D.A., Modulation of adipose tissue thermogenesis as a method for increasing energy expenditure. Bioorg. Med. Chem. Lett. 24 (2014), 425–429.
25. Shabalina, I.G., Petrovic, N., de Jong, J.M., Kalinovich, A.V., Cannon, B., Nedergaard, J., UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep. 5 (2013), 1196–1203.
26. Sharp, L.Z., Shinoda, K., Ohno, H., Scheel, D.W., Tomoda, E., Ruiz, L., Hu, H., Wang, L., Pavlova, Z., Gilsanz, V., Kajimura, S., Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS ONE, 7, 2012, e49452.
27. Véniant, M.M., Hale, C., Helmering, J., Chen, M.M., Stanislaus, S., Busby, J., Vonderfecht, S., Xu, J., Lloyd, D.J., FGF21 promotes metabolic homeostasis via white adipose and leptin in mice. PLoS ONE, 7, 2012, e40164.
28. Wu, A.L., Kolumam, G., Stawicki, S., Chen, Y., Li, J., Zavala-Solorio, J., Phamluong, K., Feng, B., Li, L., Marsters, S., et al. Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1. Sci. Transl. Med., 3, 2011, 113ra126.
29. Xu, J., Lloyd, D.J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.S., Lindberg, R.A., et al. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes 58 (2009), 250–259.