Characterization of a model to induce hyperlipidemia in feed-restricted dairy cows

Hepatic lipidosis is a prevalent metabolic disorder, and in vivo models to study intermediary lipid metabolism are needed in dairy cows. Objectives were to apply a method to induce hyperlipidemia and characterize the responses and safety of the intervention in feed-restricted dry Holstein cows at 8 mo of gestation. It was hypothesized that infusion of tyloxapol would induce hyperlipidemia without deleterious effects on health of dairy cows. Pregnant, nonlactating parous Holstein cows (n = 33) at a mean (± standard deviation) of 234 ± 2.2 d of gestation were fed for ad libitum intake on d 1 to 5 and restricted to 41% of the required NE_L from d 6 to 13. On d 14, when cows were 247 ± 2.2 d of gestation, cows were kept off feed, and received i.v. a 10% solution of tyloxapol at 120 mg/kg body weight to block hydrolysis of triacylglycerols in very-low-density lipoprotein (VLDL) particles. Blood was sampled for 720 min and analyzed for concentrations of triacylglycerol, VLDL cholesterol, and total cholesterol in serum to reflect hepatic secretion or reduced clearance of such metabolites from blood. Rectal temperature, respiration and heart rates, and clinical signs related to potential anaphylaxis were monitored for the first 30 min relative to tyloxapol infusion, and for any abnormal behavior in the subsequent 24 h. Infusion of tyloxapol progressively increased the concentrations of triacylglycerol, VLDL cholesterol, and total cholesterol in serum. Tyloxapol increased rectal temperature by 0.19°C at 30 min after infusion and increased respiration and heart rates in the first 10 min after infusion by 29% and 40%, respectively. Tyloxapol induced tachycardia (heart rate >80 beats/min) in 66.7% (n = 22), frothy salivation in 39.4% (n = 13), muzzle twitching in 15.2% (n = 5), eyes twitching in 12.1% (n = 4), muscle twitching in 48.5% (n = 16), nystagmus in 6.1% (n = 2), signs of hyperexcitement in 18.2% (n = 6), staggering gait in 18.2% (n = 6), and anaphylaxis in 12.1% (n = 4) of the cows; however, all these signs were transient, and cows returned to normal after 20 min of infusion. No other abnormal behavior was observed past 20 min of tyloxapol infusion. None of the cows aborted and gestation length, calf birth weight, and risk of diseases in the first 21 d postpartum did not differ between cows receiving tyloxapol and a companion group that did not receive tyloxapol. Infusion of tyloxapol induced hyperlipidemia in cows with some animals showing transient reactions to the treatment, but without complications to the cow and the offspring. Application of this model can be useful to study intermediary lipid metabolism in dairy cows.