Effects of the peroxisome proliferator-activated receptor-α agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves

N. B. Litherland, M. Bionaz, R. L. Wallace, J. J. Loor, J. K. Drackley

Research output: Contribution to journalArticlepeer-review


Peroxisome proliferator-activated receptor-α (PPARα) agonists increase fatty acid oxidation in liver of nonruminants. If similar effects occur in dairy cattle, enhanced hepatic oxidative capacity could decrease circulating nonesterified fatty acids and hepatic triacylglycerol accumulation in periparturient cows. The objectives of this study were 1) to determine whether partitioning of fatty acid metabolism by liver slices from weaned Holstein calves treated with PPARα agonists in vivo is altered compared with partitioning by liver slices from control (untreated) calves, and 2) to measure in vitro metabolism of palmitate and oleate by bovine liver slices and relate these to mRNA abundance for key enzymes. Weaned male Holstein calves (7 wk old; n=15) were assigned to 1 of 3 groups for a 5-d treatment period: control (untreated), clofibrate (62.5 mg/kg of BW), or fish oil (250 mg/kg of BW). Calves treated with clofibrate consumed less dry matter. Body weight, liver weight, liver weight:body weight ratio, blood nonesterified fatty acids, β-hydroxybutyrate, and liver composition were not significantly different among treatments. Liver slices were incubated for 2, 4, and 8h to determine in vitro conversion of [1-14C] palmitate and [1-14C] oleate to CO2, acid-soluble products, esterified products, and total metabolism. In liver slices incubated for 8h, conversion of palmitate to CO2 was greater for calves treated with clofibrate compared with control calves or calves treated with fish oil. Conversion of palmitate to esterified products, total palmitate metabolism, and metabolism of oleate were not different among treatments. Conversion of palmitate to CO2 was greater than that from oleate for all treatments, but rates of total metabolism did not differ. Clofibrate increased or tended to increase liver expression of several PPARα target genes involved in fatty acid oxidation (e.g., ACADVL, ACOX1, CPT1A), whereas fish oil did not significantly affect genes associated with fatty acid oxidation but tended to increase DGAT1. Overall, our data indicated that bovine liver responded to clofibrate treatment but not fish oil, although increases in hepatic lipid metabolism were much less than those reported in rodents treated with clofibrate or fish oil. Applications of PPARα agonists may be of interest to increase the rate of hepatic fatty acid oxidation and decrease triacylglycerol accumulation in periparturient dairy cows.

Original languageEnglish (US)
Pages (from-to)2404-2418
Number of pages15
JournalJournal of Dairy Science
Issue number6
StatePublished - Jun 2010


  • Dairy calf
  • Fatty acid metabolism
  • Liver
  • Peroxisome proliferator-activated receptor-α

ASJC Scopus subject areas

  • Food Science
  • Animal Science and Zoology
  • Genetics


Dive into the research topics of 'Effects of the peroxisome proliferator-activated receptor-α agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves'. Together they form a unique fingerprint.

Cite this