Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis

Research output: Contribution to journalArticle

Authors

  • Mikiko Watanabe
  • Garima Singhal
  • Ffolliott M. Fisher
  • Thomas C. Beck
  • Donald A. Morgan
  • Fabio Socciarelli
  • Marie L. Mather
  • Renata Risi
  • Jared Bourke
  • Kamal Rahmouni
  • Owen P. McGuinness
  • Jeffrey S. Flier
  • Eleftheria Maratos-Flier

External Institution(s)

  • Harvard University
  • University of Rome La Sapienza
  • Vanderbilt University
  • University of Iowa
  • Karolinska Institutet

Details

Original languageEnglish (US)
Pages (from-to)95-108
Number of pages14
JournalEndocrine
Volume67
Issue number1
StatusPublished - Jan 1 2020
Peer-reviewedYes

Abstract

Background: Fibroblast growth factor 21 (FGF21) is expressed in several metabolically active tissues, including liver, fat, and acinar pancreas, and has pleiotropic effects on metabolic homeostasis. The dominant source of FGF21 in the circulation is the liver. Objective and methods: To analyze the physiological functions of hepatic FGF21, we generated a hepatocyte-specific knockout model (LKO) by mating albumin-Cre mice with FGF21 flox/flox (fl/fl) mice and challenged it with different nutritional models. Results: Mice fed a ketogenic diet typically show increased energy expenditure; this effect was attenuated in LKO mice. LKO on KD also developed hepatic pathology and altered hepatic lipid homeostasis. When evaluated using hyperinsulinemic-euglycemic clamps, glucose infusion rates, hepatic glucose production, and glucose uptake were similar between fl/fl and LKO DIO mice. Conclusions: We conclude that liver-derived FGF21 is important for complete adaptation to ketosis but has a more limited role in the regulation of glycemic homeostasis.

    Research areas

  • Adipose tissue, Cholesterol, Energy metabolism, Fibroblast Growth Factor 21, Ketogenic diet, Nonalcoholic fatty liver disease

Citation formats

APA

Watanabe, M., Singhal, G., Fisher, F. M., Beck, T. C., Morgan, D. A., Socciarelli, F., ... Maratos-Flier, E. (2020). Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis. Endocrine, 67(1), 95-108. https://doi.org/10.1007/s12020-019-02124-3

Harvard

Watanabe, M, Singhal, G, Fisher, FM, Beck, TC, Morgan, DA, Socciarelli, F, Mather, ML, Risi, R, Bourke, J, Rahmouni, K, McGuinness, OP, Flier, JS & Maratos-Flier, E 2020, 'Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis', Endocrine, vol. 67, no. 1, pp. 95-108. https://doi.org/10.1007/s12020-019-02124-3