Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver.
Fibroblast growth factors (Fgfs) are polypeptide growth factors with diverse functions. Fgf21, a unique member of the Fgf family, is expected to function as a metabolic regulator in an endocrine manner. Hepatic Fgf21 expression was increased by fasting. The phenotypes of hepatic Fgf21 transgenic or knockdown mice and high-fat, low-carbohydrate ketogenic diet-fed mice suggests that Fgf21 stimulates lipolysis in the white adipose tissue during normal feeding and is required for ketogenesis and triglyceride clearance in the liver during fasting. However, the physiological roles of Fgf21 remain unclear. To elucidate the physiological roles of Fgf21, we generated Fgf21 knockout (KO) mice by targeted disruption. Fgf21 KO mice were viable, fertile, and seemingly normal. Food intake, oxygen consumption, and energy expenditure were also essentially unchanged in Fgf21 KO mice. However, hypertrophy of adipocytes, decreased lipolysis in adipocytes, and decreased blood nonesterified fatty acid levels were observed when Fgf21 KO mice were fed normally. In contrast, increased lipolysis in adipocytes and increased blood nonesterified fatty acid levels were observed in Fgf21 KO mice by fasting for 24 h, indicating that Fgf21 stimulates lipolysis in the white adipose tissue during feeding but inhibits it during fasting. In contrast, unexpectedly, hepatic triglyceride levels were essentially unchanged in Fgf21 KO mice. In addition, ketogenesis in Fgf21 KO mice was not impaired by fasting for 24 h. The present results indicate that Fgf21 regulates lipolysis in adipocytes in response to the metabolic state but is not required for ketogenesis and triglyceride clearance in the liver.
Hotta
Yuhei
Y
Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto 606-8501, Japan.
Nakamura
Hirotoshi
H
Konishi
Morichika
M
Murata
Yusuke
Y
Takagi
Hiroyuki
H
Matsumura
Shigenobu
S
Inoue
Kazuo
K
Fushiki
Tohru
T
Itoh
Nobuyuki
N
D017667:Adipocytes / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D005215:Fasting / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D015870:Gene Expression; D055786:Gene Knockout Techniques; D006003:Glycogen / Q000378:metabolism; D007657:Ketone Bodies / Q000096:biosynthesis; D008066:Lipolysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D014280:Triglycerides / Q000378:metabolism
D007657:Ketone Bodies; D014280:Triglycerides; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D006003:Glycogen