Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver
Abstract
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.
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Under fasted conditions, FGF21 increases hepatic gluconeogenesis, β-oxidation, and ketogenesis in mice.
“Under fasted conditions, FGF21 increases hepatic gluconeogenesis, β-oxidation, and ketogenesis in mice [142,154].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [142]
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- Authors
- Hotta, Y., Nakamura, H., Konishi, M., Murata, Y., Takagi, H., Matsumura, S., Inoue, K., Fushiki, T., & Itoh, N.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Konishi, Morichika
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-07-09
- Volume
- 150
- Issue
- 10
- Pages
- 4625-4633
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2042911346
- Cited by
- 352
- References
- 25
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 20 · 2023: 14 · 2022: 19 · 2021: 13 · 2020: 18 · 2019: 25 · 2018: 27 · 2017: 28 · 2016: 27 · 2015: 30 · 2014: 24 · 2013: 23 · 2012: 30
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- FGF21, lipolysis, white adipose tissue, ketogenesis, triglyceride clearance, liver, fasting, free fatty acids, adipocyte hypertrophy, FGF21 knockout mice, energy metabolism, ketogenic diet
- MeSH terms
- Animals, Fasting, Fibroblast Growth Factors, Glycogen, Ketone Bodies, Lipolysis, Liver, Male, Mice, Inbred C57BL, Phenotype, Triglycerides, Gene Expression, Adipocytes, Mice, Knockout, Mice, Adipose Tissue, White, Gene Knockout Techniques
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