The APOB loss-of-function mutation of Holstein dairy cattle does not cause a deficiency of cholesterol but decreases the capacity for cholesterol transport in circulation.

The loss-of-function mutation of the apolipoprotein (APO) B gene (APOB) in Holstein cattle accounts for increased losses in calves that are homozygous for this mutation. Heterozygous carriers of the APOB mutation are clinically healthy but show decreased concentrations of plasma cholesterol and lipoproteins. So far, the metabolic effects of the mutation have only been investigated in heterozygous calves, bulls, and nonlactating females. In high-yielding dairy cows, a marked decrease in cholesterol concentration in plasma during early lactation is part of the usual metabolic changes. Given the essential role of cholesterol in fatty acid and lipid metabolism, a specific effect of the APOB mutation on metabolism and performance in dairy cows is expected. Therefore, the aim of the present study was to investigate the effects of different APOB genotypes on metabolic parameters, hepatic metabolism, and lactation and reproductive performance. Twenty pairs of full siblings with similar age, performance, and calving were investigated. Both animals of each pair were kept on the same farm and consisted of a heterozygous carrier (CDC) and a noncarrier (CDF) of the APOB mutation associated with cholesterol deficiency. Blood samples were taken in early (25.5 ± 4.7 d in milk) and mid lactation (158.2 ± 11.1 d in milk; mean ± SD), and analyzed for nonesterified fatty acids, ß-hydroxybutyrate, glucose, insulin-like growth factor-1, aspartate aminotransferase and gamma-glutamyltransferase activity, total cholesterol, free cholesterol, triacylglycerols, high density lipoprotein-cholesterol, and phospholipids. The evaluation of milk production, milk gross composition, and lactation persistency was based on official Dairy Herd Improvement Association recordings. Cholesterol and lipoprotein concentrations were lower in CDC cows than in CDF cows in early and mid lactation. Metabolic parameters, triacylglycerol concentration in plasma, and lactation and reproductive performance did not differ between CDC cows and CDF cows. The low cholesterol concentrations associated with the APOB mutation in heterozygous carriers are not because of a primary deficiency of cholesterol at a cellular level, as the term "cholesterol deficiency" suggests, but rather a consequence of reduced capacity for its transport in circulation. Overall, the data of the present study suggest that, despite the presence of the APOB mutation, cholesterol is not limiting for animals' metabolic adaptation and performance in heterozygous Holstein cows.