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Cholesterol Metabolism, Transport and hepatic Regulation during negative Energy Balance in early and mid-lactation in Dairy Cows
The negative energy balance (NEB) in early lactation has considerable effects on the cholesterol metabolism of dairy cows. The objective of this study was to investigate the response of plasma and milk lipids, enzyme activities and hepatic mRNA expression of transcripts encoding for factors involved in cholesterol metabolism to a NEB in early and mid-lactation. Fifty multiparous Holstein dairy cows (25 control (C), 25 feed-restricted (R)) were studied from wk 1 pp until 17 pp with an almost 50% feed-restriction from wk 14 to 17 pp. Blood samples, liver biopsies and milk samples were taken in wk 1, 14 and 17 pp. Blood and milk lipid concentrations [triglycerides (TG), cholesterol, lipoproteins] and enzyme activities [phospholipid transfer protein (PLTP), lecithin-cholesterol acyltransferase (LCAT)] related to cholesterol homeostasis were analyzed. Hepatic gene expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMGC) synthase 1 (HMGCS1) and HMGC reductase (HMGCR), sterol regulatory element-binding factor (SREBF) -2, microsomal triglyceride transfer protein (MTTP), ATP-binding cassette transporter (ABC) A1 and ABCG1 were measured. While values were lower for cows in wk 1 pp, plasma concentrations of TG, cholesterol, VLDL-cholesterol (VLDL-C) and LDL-C increased in R cows from wk 14 to 17 pp compared to C cows. Whereas in wk 1 pp PLTP activity was increased and LCAT activity was lower, activities of PLTP and LCAT did not differ between wk 14 and 17 pp in C and R cows. Cholesterol concentration in milk did not change from wk 14 to 17 pp, whereas cholesterol mass in milk was decreased in wk 17 pp for R cows and tended to be lower in R cows compared to C cows. On the contrary, cholesterol concentration and mass in milk were higher in wk 1 pp. SREBF-2, HMGCS1, HMGCR, MTTP, ABCA1 and -G1 showed no changes during the experiment. In contrast, during the NEB at the onset of lactation the expression of HMGCS1, HMGCR, SREBF-2 and ABCA1 were increased. In conclusion, increased plasma concentrations of TG, cholesterol, VLDL-C, and LDL-C during the feed restriction period suggest that in later stages of lactation the liver is able to enhance the export of generated TG as VLDL. The diminished milk cholesterol mass might represent a measure to save cholesterol for the constitution of VLDL.
Keywords: cholesterol metabolism, lipoprotein, dairy cow