Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows

Abstract

Dairy cows are highly susceptible after parturition to developing liver lipidosis and ketosis, which are costly diseases to farmers. A bovine microarray platform consisting of 13,257-annotated oligonucleotides was used to study hepatic gene networks underlying nutrition-induced ketosis. On day 5 postpartum, 14 Holstein cows were randomly assigned to ketosis-induction (n = 7) or control (n = 7) groups. Cows in the ketosis-induction group were fed at 50% of day 4 intake until they developed signs of clinical ketosis, and cows in the control group were fed ad libitum throughout the treatment period. Liver was biopsied at 10-14 (ketosis) or 14 days postpartum (controls). Feed restriction increased blood concentrations of nonesterified fatty acids and beta-hydroxybutyrate, but decreased glucose. Liver triacylglycerol concentration also increased. A total of 2,415 genes were altered by ketosis (false discovery rate = 0.05). Ingenuity Pathway Analysis revealed downregulation of genes associated with oxidative phosphorylation, protein ubiquitination, and ubiquinone biosynthesis with ketosis. Other molecular adaptations included upregulation of genes and nuclear receptors associated with cytokine signaling, fatty acid uptake/transport, and fatty acid oxidation. Genes downregulated during ketosis included several associated with cholesterol metabolism, growth hormone signaling, proton transport, and fatty acid desaturation. Feed restriction and ketosis resulted in previously unrecognized alterations in gene network expression underlying key cellular functions and discrete metabolic events. These responses might help explain well-documented physiological adaptations to reduced feed intake in early postpartum cows and, thus, provide molecular targets that might be useful in prevention and treatment of liver lipidosis and ketosis.

Influence of feed intake on blood chemistry parameters in Kacang goats

“…It is reported that intake restriction resulted in a significant decrease of blood glucose concentration in cattle [12,13], in diary cows [14], deer [4] and horse [15]. Furthermore, previous studies also showed that reduced feed consumption resulted in metabolic disorder in cattle, sheep, deer, ilama, and rats [3,4,5,6], disturbance of acid-base balance of body fluids [7], and hepatic lipidosis [8]. Furthermore, the ADG of of the Kacang goats during the refeeding period was 0.11±0.05 kg/day and showed that the body weight of the Kacang goats increased significantly.…”

“…Previous studies showed that reduced feed or protein consumption resulted in metabolic disorder in cattle, sheep, deer, ilama, and rats indicated by alteration of some blood chemistry profiles, such as glucose, lipid and protein [3,4,5,6] and in disturbance of acid-base balance of body fluids [7]. Moreover, study in cattle revealed that feed restriction might lead to the occurrence of hepatic lipidosis [8].…”

Some blood markers of the functional state of liver in dairy cows with clinical ketosis

“…Moreover, ketosis is a polyetiological disease, often complicated by other diseases. Impaired functions of liver, pancreatic gland, other organs are often observed in sick animals (Steen, 2001;Stojević et al, 2005;Loor et al, 2007;Gonzalez & Rosendo, 2013) which may complicate diagnostics and further treatment.…”

Cattle genomics and its implications for future nutritional strategies for dairy cattle

“…However, because restricted-energy fed cows did not experience fatty liver relative to energy-overfed cows (Loor et al, 2006) it is apparent that different signals are capable of triggering the same metabolic adaptations in liver, for example, cows with severe nutrition-induced ketosis early postpartum also upregulate fatty acid catabolism pathways in liver (Loor et al, 2007). A novel observation in cows fed restrictedenergy prepartum was the enrichment of antigen processing and presentation pathways enriched in a cluster of clearly upregulated genes.…”

“…An initial characterization of liver transcriptional adaptations to saturated v. polyunsaturated fatty acid supplementation at 210, 1 and ,14 days relative to parturition with a bovine microarray (Loor et al, 2007) has revealed some unique adaptations (Khan et al, 2010). Treatment diets were fed from 21 days before expected date of parturition until ,10 days after parturition (Ballou et al, 2009).…”