Etiology of fatty liver in dairy cattle: Effects of nutritional and hormonal status on hepatic microsomal triglyceride transfer protein

We conducted three experiments to determine the effects of nutritional and hormonal status on microsomal triglyceride transfer protein (MTP) activity and mass. In experiment 1, 18 nonlactating Holstein cows, 75 d before expec ted calving date, in their second gestation or greater were monitored from d 75 to 55 prepartum. Cows were fed a control diet from d 75 to 62 prepartu m for covariable measurements. From d 61 to 55 prepartum, six cows continue d to receive the control diet, six cows were restricted to 2.3 kg of grass hay/d, and six cows were fed the control diet plus 1.8 kg of concentrate/d and 500 ml of propylene glycol given 2 times/d as an oral drench. Plasma gl ucose and serum insulin concentrations were highest in cows that received p ropylene glycol and lowest in feed restricted cows. Plasma nonesterified fa tty acids (NEFA) and liver triglyceride (TG) concentrations were highest in feed restricted cows and not different between cows that received the cont rol diet and cows that received propylene glycol. Hepatic MTP activity and mass were not affected by treatment in experiment 1. In experiment 2, bovin e hepatocytes isolated from the caudate process of five preruminating Holst ein bull calves were incubated with either 0, 0.5, 1.0, or 2.0 mM NEFA for 48 h. Intracellular TG increased linearly as NEFA concentration in the medi a increased. Concentration of NEFA in the incubation media had no effect on MTP activity or mass. There was a quadratic effect of concentration of NEF A in the incubation media on MTP mRNA. In experiment 3, bovine hepatocytes isolated from the caudate process of five preruminating Holstein bull calve s were incubated with 2 mM [1-C-14]oleate for 24 h to accumulate TG, follow ed by a 36-h period of TG depletion, during which hepatocytes were incubate d with no hormone, 10 nM insulin, or 10 nM glucagon. There was no effect of insulin or glucagon on intracellular TG;, MTP activity or mass. Cells incu bated with no hormone had higher levels of MTP mRNA compared to cells incub ated with insulin or glucagon during the depletion period. Results suggest that hepatic MTP mRNA may be affected by TG accumulation, insulin, and gluc agon in vitro. However, hepatic MTP activity and mass are not affected by n utritional status of nonlactating dairy cows, TG accumulation in vitro, or insulin and glucagon in vitro.