Cited by 252Fibroblast Growth Factor ResearchLipid metabolism and disordersAdipose Tissue and Metabolism

FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues

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Schlein, Christian, Talukdar, Saswata, Heine, Markus, Fischer, Alexander W., Krott, Lucia M., Nilsson, Stefan K., Brenner, Martin B., Heeren, Joerg +1 more·2016·Cell Metabolism

Abstract

FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT.

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Crossref · 10.1016/j.cmet.2016.01.006

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  • FGF21's triglyceride-lowering effects are mediated by altered adipose and liver metabolism: accelerated lipoprotein catabolism, suppression of postprandial lipolysis, decreased hepatic ER and oxidative stress, and increased beta-oxidation of lipids in the liver.

    “Pharmacological administration of FGF21 or FGF21 analogues exerts lipid-lowering effects through accelerated lipoprotein catabolism108, suppression of postprandial lipolysis in adipose tissues88, decreased hepatic endoplasmic reticulum and oxidative stress109,110, and increased beta-oxidation of lipids in the liver62”

    From Metabolic messengers: FGF21 (2021) · cites this paper as [108]

  • The potent effects of FGF21 on lipid metabolism are also present in adipose-specific Klb knockout mice.

    “In addition, the potent effects of FGF21 on lipid metabolism (115) are also present in adipose-specific Klb knockout mice (11).”

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Authors
Schlein, C., Talukdar, S., Heine, M., Fischer, A. W., Krott, L. M., Nilsson, S. K., Brenner, M. B., Heeren, J., & Scheja, L.
Affiliations
  • University Medical Center Hamburg-Eppendorf (DE)
  • Pfizer (United States) (US)
Corresponding author
Scheja, Ludger
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2016-03
Volume
23
Issue
3
Pages
441-453
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2253407701
Cited by
252
References
53
Citations by year
2026: 18 · 2025: 18 · 2024: 27 · 2023: 20 · 2022: 26 · 2021: 27 · 2020: 30 · 2019: 33 · 2018: 19 · 2017: 21 · 2016: 11
FWCI
14.55
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
FGF21, plasma triglycerides, triglyceride-rich lipoproteins, lipoprotein catabolism, white adipose tissue, brown adipose tissue, CD36, lipoprotein lipase, free fatty acids, hepatic lipid metabolism, insulin resistance, diet-induced obesity, ob/ob mice
MeSH terms
Animals, Hypolipidemic Agents, Adipose Tissue, Brown, Cells, Cultured, Drug Evaluation, Preclinical, Female, Fibroblast Growth Factors, Humans, Lipoproteins, VLDL, Liver, Male, Mice, Inbred C57BL, Triglycerides, Mice, Knockout, Hepatocytes, Lipid Metabolism, Adipose Tissue, White, Adipocytes, White

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