Palmitic acid feeding increases ceramide availability in association with increased milk yield, NEFA availability, and adipose tissue responsiveness to a glucose challenge

Abstract Text: Reduced insulin action facilitates glucose partitioning for milk synthesis and facilitates lipolysis during early lactation. Insulin sensitivity increases beyond peak milk yield, while circulating NEFA and milk production decline. Palmitic acid (C16:0) promotes insulin resistance in monogastrics through ceramide-dependent mechanisms, and ceramides are elevated in hyperlipidemic insulin resistant early lactation cows. We hypothesized that feeding C16:0 to mid-lactation cows would enhance circulating ceramide, and ceramide would be positively associated with milk yield. Twenty multiparous Holstein cows were enrolled in a study consisting of a 5 d covariate, 49 d treatment, and 14 d post-treatment evaluation. Cows were randomly assigned to a sorghum silage-based diet containing no supplemental fat (control; n =10; 138 ±45 DIM) or C16:0 at 4% of ration DM (PALM; 98% C16:0; n =10; 136 ±44 DIM). Blood was collected at routine intervals and milk yields were recorded. Intravenous glucose tolerance tests (GTT) were performed at d -1, 21, and 49 relative to start of treatment. Plasma sphingolipids were quantified using liquid chromatography tandem mass spectrometry. Data were analyzed as repeated measures using a mixed model (fixed effects of treatment and time). Pearson correlations were analyzed. The most abundant sphingolipids included C24:0-ceramide, C24:0-monohexosylceramide (GlcCer), and C16:0-lactosylceramide (LacCer). Relative to control, plasma concentrations of total ceramide, GlcCer, and LacCer decreased as lactation progressed (P <0.01). Total ceramide and C24:0-ceramide were increased by d 8 of treatment in PALM, and remained elevated throughout the 7 wk treatment period (+80% average; P <0.001). Similarly, C16:1-, C22:0-, C22:1-, C24:1-, and C26:0-ceramide levels were greater in PALM (P <0.05). Post-treatment, total ceramide concentrations in PALM returned to control levels. PALM increased total GlcCer and C24:0-GlcCer levels in plasma by 32 and 33% at wk 3 and 7, respectively (P <0.01). Also, PALM increased C16:0-, C22:0-, C22:1-, and C24:1-GlcCer in plasma (P <0.01), but had no effect on LacCer levels. We observed a decline in GlcCer and LacCer concentrations as lactation progressed (e.g., C24:0-GlcCer; P <0.01). Plasma C24:0-ceramide was positively correlated with plasma NEFA and milk yield, and inversely correlated with NEFA disappearance following GTT (r =0.52, 0.44, and -0.57, respectively; P <0.001), relationships shared by most detected ceramides. We conclude that increasing C16:0 intake to augment ceramide supply delayed the decline in ceramide supply observed with the progression of lactation. Future research should evaluate whether ceramide is intrinsically involved in the homeorhetic adaptation to lactation.

Keywords:

ceramide

insulin resistance

lactation