title: Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tomlinson
authors.forename: Ling
authors.initials: L
authors.lastname: Fu
authors.forename: Linu
authors.initials: L
authors.lastname: John
authors.forename: Bruce
authors.initials: B
authors.lastname: Hultgren
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Huang
authors.forename: Mark
authors.initials: M
authors.lastname: Renz
authors.forename: Jean Philippe
authors.initials: JP
authors.lastname: Stephan
authors.forename: Saio Ping
authors.initials: SP
authors.lastname: Tsai
authors.forename: Lyn
authors.initials: L
authors.lastname: Powell-Braxton
authors.forename: Dorothy
authors.initials: D
authors.lastname: French
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Stewart
mesh_terms: 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
chemical_list: 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