Circulating low-density lipoprotein ceramide concentrations increase in Holstein dairy cows transitioning from gestation to lactation

Abstract

Low-density lipoprotein (LDL) ceramide causes insulin resistance in obese diabetic nonruminants. Because previous work suggests that liver-derived ceramide may impair insulin action in postpartum cows, our objectives were to characterize peripartal changes in lipoprotein ceramides. We further studied the effects of prepartum adiposity on lipoprotein ceramide levels. Twenty-eight pregnant Holstein cows (parity = 3.65 ± 1.62) with lean (body condition score, BCS = 2.97 ± 0.16; body weight, BW = 630 ± 55.2 kg; n = 15) or overweight (BCS = 3.93 ± 0.27; BW = 766 ± 46.1 kg; n = 13) body condition 28 d before expected parturition were evaluated. Sampling occurred on d -20.5 ± 1.74, -13.8 ± 1.71, -7.84 ± 4.07, -6.71 ± 1.00, -3.92 ± 0.64, and -1.28 ± 0.61 (before parturition); daily until d 8 postpartum; and on d 10, 12, 14, 21, and 28. Adipose tissue and liver were biopsied on d -7.84 ± 4.07 and 10. Postpartum insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp. Lipoprotein fractions were isolated using liquid chromatography. Sphingolipids were quantified using mass spectrometry. Data were analyzed using a mixed model with repeated measures. Overweight cows had a higher BCS and BW at enrollment relative to lean cows, but BCS and BW were similar postpartum. Overweight cows lost more body condition (0.97 ± 0.36 vs. 0.55 ± 0.16 BCS units) and BW (291 ± 67.3 vs. 202 ± 54.5 kg) during transition relative to lean cows. Adipocyte volume and counts declined from prepartum to postpartum (50.4 and 13.7%, respectively), and adipocyte volume was greater (48.2%) in overweight cows prepartum relative to lean cows. Although DMI was comparable between BCS groups, milk yield tended to be greater in overweight cows. Plasma free fatty acid and β-hydroxybutyrate and liver lipid levels were 40, 16, and 37% greater, respectively, in overweight cows compared with lean cows. Glucose infusion rate during the hyperinsulinemic-euglycemic clamp tended to be lower in overweight cows. Ceramide levels within triacylglycerol-rich lipoprotein fractions declined postpartum, whereas LDL ceramide increased postpartum. Overweight cows had lower triacylglycerol-rich lipoprotein C16:0-ceramide levels relative to lean cows. Prepartum LDL C24:0-ceramide levels were greater in overweight cows relative to lean cows. Independent of prepartum adiposity, we concluded that serum LDL ceramide levels are elevated in early-lactation cows experiencing adipose tissue free fatty acid mobilization and hepatic steatosis.