Effect of circulating glucagon and free fatty acids on hepatic FGF21 production in dairy cows

Luciano S. Caixeta, Sarah L. Giesy, Christopher S. Krumm, James W. Perfield, Anthony Butterfield, Katie M. Schoenberg, Donald C. Beitz, Yves R. Boisclair

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Modern dairy cows meet the energy demand of early lactation by calling on hormonally driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and nonesterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy-sufficient, nonpregnant, nonlactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over a 72-h period. GCG increased hepatic FGF21 mRNA by an average of fivefold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with Intralipid and injected with saline, or infused with Intralipid and injected with GCG. Infusions and injections were administered intravenously over 16 h and subcutaneously every 8 h, respectively. Intralipid infusion increased plasma NEFA from 92 to 550 μM within 3 h and increased plasma FGF21 from 1.3 to >11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the Intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA, or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation.

Original languageEnglish (US)
Pages (from-to)R526-R534
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5
StatePublished - Nov 2017

Bibliographical note

Funding Information:
This material is based on work that is supported by the National Institute of Food and Agriculture, US Department of Agriculture, under award number 2010-65206-20683 and Hatch/Multistate project under 1000962.

Publisher Copyright:
© 2017 the American Physiological Society.


  • Early lactation
  • Late pregnancy
  • Liver
  • Plasma fibroblast growth factor-21


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