Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.
The fibroblast growth factors (FGFs), and the corresponding receptors, are implicated in more than just the regulation of epithelial cell proliferation and differentiation. Specifically, FGF23 is a regulator of serum inorganic phosphate levels, and mice deficient in FGF receptor-4 have altered cholesterol metabolism. The recently described FGF19 is unusual in that it is nonmitogenic and appears to interact only with FGF receptor-4. Here, we report that FGF19 transgenic mice had a significant and specific reduction in fat mass that resulted from an increase in energy expenditure. Further, the FGF19 transgenic mice did not become obese or diabetic on a high fat diet. The FGF19 transgenic mice had increased brown adipose tissue mass and decreased liver expression of acetyl coenzyme A carboxylase 2, providing two mechanisms by which FGF19 may increase energy expenditure. Consistent with the reduction in expression of acetyl CoA carboxylase 2, liver triglyceride levels were reduced.
Tomlinson
Elizabeth
E
Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
Fu
Ling
L
John
Linu
L
Hultgren
Bruce
B
Huang
Xiaojian
X
Renz
Mark
M
Stephan
Jean Philippe
JP
Tsai
Saio Ping
SP
Powell-Braxton
Lyn
L
French
Dorothy
D
Stewart
Timothy A
TA
D000273:Adipose Tissue / Q000187:drug effects / Q000502:physiology*; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D002153:Calorimetry, Indirect; D003920:Diabetes Mellitus / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype
D004041:Dietary Fats; C117476:FGF19 protein, human; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005947:Glucose