title: Transcript profiling of the ruminant liver indicates a unique program of transcriptional regulation of ketogenic enzymes during food restriction.
abstract: Ruminants absorb little glucose and rely on hepatic gluconeogenesis and ketogenesis in the fed state to convert short-chain fatty acids produced during digestion into glucose and ketone bodies, respectively. In contrast to the non-ruminant response, fluxes through gluconeogenic and ketogenic pathways decrease during food restriction. Transcriptional regulation responsible for these unique food restriction responses has not been established. To determine the hepatic transcriptional response of ruminants to an acute drop in dietary nutrient supply, 102 yearling heifers were assigned to either ad libitum feeding or 24 h of food withdrawal in a randomized block design. Liver biopsies were obtained for microarray and quantitative real-time PCR analyses of gene expression. Plasma concentrations of non-esterified fatty acids were higher in food restricted heifers, while levels of β-hydroxybutyrate, triacylglycerol, and glucose were decreased. Despite a decline in substrate supply and a lower hepatic production of glucose, expression of the key gluconeogenic enzymes pyruvate carboxylase, phosphoenolpyruvate carboxykinase and fructose-1,6-bisphosphatase was upregulated as in non-ruminants. Downregulation of cholesterolgenic genes and upregulation of fatty acid oxidative genes were consistent with SREBP-2 and PPARα control, respectively. Ketogenesis from short-chain fatty acids was downregulated, contrary to the non-ruminant response to food restriction. Short-chain fatty acids may exert transcriptional control in the ruminant liver similar to that demonstrated in the large intestine of non-ruminants.
authors: Department of Animal and Poultry Science, University of Guelph, Ontario, Canada N1G 2W1.
authors: John
authors: J
authors: Doelman
authors: Honghe
authors: H
authors: Cao
authors: Norman G
authors: NG
authors: Purdie
authors: Julie J M
authors: JJ
authors: Kim
authors: Kendall C
authors: KC
authors: Swanson
authors: Vernon R
authors: VR
authors: Osborne
authors: Jasper
authors: J
authors: Tey
authors: Ayesha
authors: A
authors: Ali
authors: Zeny
authors: Z
authors: Feng
authors: Niel A
authors: NA
authors: Karrow
authors: John P
authors: JP
authors: Cant
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D031204:Caloric Restriction; D002417:Cattle; D005230:Fatty Acids, Nonesterified / Q000097:blood; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007657:Ketone Bodies / Q000096:biosynthesis* / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055442:Metabolome / Q000235:genetics; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D012418:Ruminants / Q000097:blood / Q000235:genetics*; D014158:Transcription, Genetic; D014280:Triglycerides / Q000097:blood
chemical_list: D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D012333:RNA, Messenger; D014280:Triglycerides; D020155:3-Hydroxybutyric Acid