Thursday, January 10, 2013
Figure 1. FGF21 gets detailed. Researchers from Amgen Inc. and Roche's Genentech Inc.
unit have separately published studies that suggest using antibodies to mimic fibroblast growth factor 21
(FGF21) action could
help treat metabolic diseases, including type 2 diabetes and obesity.
addition, separate teams at Eli Lilly and Co.,
Harvard Medical School and The University of Texas Southwestern Medical Center have
elucidated downstream cellular functions that help explain how FGF21 exerts its
adipose tissue, FGF21 binds to and activates an FGF receptor 1c isoform
(FGFR1c) and klotho-b (KLB) complex [a].
This triggers a signaling cascade that leads to activation of peroxisome
proliferation-activated receptor-g (PPARG;
1a (PPARGC1A; PGC-1a) [b]. These transcriptional
regulators then act to upregulate downstream targets that trigger uptake of
glucose, browning of white adipose tissue, induction of thermogenesis and
increases in oxidative metabolism [c].
monkeys, an Amgen antibody designed to specifically activate the FGFR1c and KLB
complex mimicked the antidiabetic actions of FGF21. In mice, adipocyte-specific
deletion of Fgfr1c blocked the blood glucose-lowering effects of Fgf21
compared with no deletion. Together, these results suggest that targeting the
FGFR1c and KLB complex in adipocytes is primarily responsible for the therapeutic
action of FGF21.