Characterization of peripartum liver and skeletal muscle ceramide concentrations in lean and overweight Holstein dairy cows

Abstract Text:

Circulating sphingolipid ceramide is associated with the development of insulin resistance in overweight monogastrics. An increase in NEFA delivery to liver can increase lipoprotein ceramide packaging and secretion. In turn, lipoprotein ceramide can antagonize insulin action in skeletal muscle. We recently discovered that ceramide increases concomitantly with hyperlipidemia in overweight cows transitioning from gestation to lactation. Considering evidence in monogastrics, our objective was to characterize the relationship between adiposity, and liver and skeletal muscle ceramide concentrations. Multiparous Holstein cows were grouped by adiposity at d -28 prepartum as either lean (2.9 ±0.1 BCS; n =7; LEAN) or overweight (4.0 ±0.2 BCS; n =7; OVER). Diets were formulated to meet or exceed requirements. Blood samples were collected routinely from d -21 to 21, relative to calving, and liver and skeletal muscle biopsies were performed at d -21, -7, and 4. Liquid chromatography tandem mass spectrometry was used to quantify ceramide, monohexosylceramide (GlcCer), and lactosylceramide (LacCer). Data were analyzed as repeated measures using a mixed model with fixed effects of adiposity and time. Pearson’s correlations were analyzed. Relative to LEAN, OVER experienced increased BCS loss, plasma NEFA, hepatic total lipid accumulation, and circulating ceramide (e.g. C24:0-ceramide) during the transition from gestation to lactation (P <0.05). Comparable to plasma, C24:0-ceramide was the most abundant ceramide in liver and muscle. To support a relationship between liver and plasma ceramides, plasma total ceramide and liver total ceramide were positively correlated during transition (r =0.39; P <0.05). Similarly, plasma C24:0-ceramide and liver C24:0-ceramide were positively correlated (r =0.41; P <0.05). Coinciding with an increase in circulating NEFA, hepatic total ceramide and C24:0-ceramide increased postpartum in OVER (P <0.05). Liver total ceramide and C24:0-ceramide were positively correlated with plasma NEFA (r =0.44 and 0.49, respectively; P <0.05). Additionally, we observed an increase in postpartum hepatic C22:0-ceramide in OVER (P <0.05). Hepatic total GlcCer tended to be increased postpartum for all cows (P =0.10), however, hepatic total LacCer only increased in LEAN (P <0.05). Muscle total ceramide and C24:0-ceramide levels were lower prepartum in OVER (P <0.05). In contrast, postpartum muscle C16:0- and C24:0-ceramide were higher in OVER (P <0.05). We conclude that enhanced lipolysis in overweight dairy cows increases hepatic ceramide synthesis to support ceramide accumulation in circulation. The ability of hepatic-derived ceramide to antagonize insulin action in extra-hepatic tissues during early lactation requires further investigation. 

Keywords:

ceramide, insulin resistance, peripartal dairy cow