Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat.
Plasma FGF21 levels and hepatic FGF21 gene expression increase dramatically after birth in mice. This induction is initiated by suckling, requires lipid intake, is impaired in PPARalpha null neonates, and is mimicked by treatment with the PPARalpha activator, Wy14,643. Neonates exhibit reduced FGF21 expression in response to fasting, in contrast to the upregulation occurring in adults. Changes in FGF21 expression due to suckling or nutritional manipulations were associated with circulating free fatty acid and ketone body levels. We mimicked the FGF21 postnatal rise by injecting FGF21 into fasting neonates, and found that this enhanced the expression of genes involved in thermogenesis within brown fat, and increased body temperature. Brown adipocytes treated with FGF21 exhibited increased expression of thermogenic genes, higher total and uncoupled respiration, and enhanced glucose oxidation. We propose that the induction of FGF21 production by the liver mediates direct activation of brown fat thermogenesis during the fetal-to-neonatal transition.
Hondares
Elayne
E
Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona and CIBER Fisiopatologia de la Obesidad y Nutrición, Barcelona, Catalonia, Spain.
Rosell
Meritxell
M
Gonzalez
Frank J
FJ
Giralt
Marta
M
Iglesias
Roser
R
Villarroya
Francesc
F
D052437:Adipocytes, Brown / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature; D005215:Fasting; D005227:Fatty Acids / Q000097:blood; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D018149:Glucose Intolerance / Q000378:metabolism; D007657:Ketone Bodies / Q000097:blood; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008892:Milk / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D012119:Respiration; D022722:Thermogenesis / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation
D001786:Blood Glucose; D005227:Fatty Acids; D007657:Ketone Bodies; D047493:PPAR alpha; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors