Document Detail

Effects of the peroxisome proliferator-activated receptor-alpha agonists clofibrate and fish oil on hepatic fatty acid metabolism in weaned dairy calves.
MedLine Citation:
PMID:  20494149     Owner:  NLM     Status:  MEDLINE    
Peroxisome proliferator-activated receptor-alpha (PPARalpha) 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 PPARalpha 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, beta-hydroxybutyrate, and liver composition were not significantly different among treatments. Liver slices were incubated for 2, 4, and 8 h to determine in vitro conversion of [1-(14)C] palmitate and [1-(14)C] oleate to CO(2), acid-soluble products, esterified products, and total metabolism. In liver slices incubated for 8 h, conversion of palmitate to CO(2) 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 CO(2) 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 PPARalpha 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 PPARalpha agonists may be of interest to increase the rate of hepatic fatty acid oxidation and decrease triacylglycerol accumulation in periparturient dairy cows.
N B Litherland; M Bionaz; R L Wallace; J J Loor; J K Drackley
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of dairy science     Volume:  93     ISSN:  1525-3198     ISO Abbreviation:  J. Dairy Sci.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-24     Completed Date:  2010-09-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985126R     Medline TA:  J Dairy Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2404-18     Citation Subset:  IM    
Copyright Information:
2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Department of Animal Sciences, University of Illinois, Urbana 61801, USA.
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MeSH Terms
Antilipemic Agents / pharmacology*
Clofibrate / pharmacology*
Fatty Acids / metabolism*
Fish Oils / pharmacology*
Gene Expression Regulation / drug effects
Lipids / analysis
Liver / chemistry,  drug effects*,  metabolism
Liver Glycogen / analysis
Oleic Acid / metabolism
Organ Size / drug effects
PPAR alpha / agonists*
Palmitates / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Triglycerides / analysis
Reg. No./Substance:
0/Antilipemic Agents; 0/Fatty Acids; 0/Fish Oils; 0/Lipids; 0/Liver Glycogen; 0/PPAR alpha; 0/Palmitates; 0/Triglycerides; 112-80-1/Oleic Acid; 637-07-0/Clofibrate

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