Adsa Logo White Adsa Title White

Effects of serine palmitoyltransferase inhibition by myriocin in ad libitum-fed and nutrient-restricted non-lactating ewes.

A. N. Davis

Events

06-23-2020

Abstract:

253
Effects of serine palmitoyltransferase inhibition by myriocin in ad libitum-fed and nutrient-restricted non-lactating ewes.
A. N. Davis*1, W. A. Myers1, J. E. Rico1, L. F. Wang1,2, C. Chang1, A. T. Richards1, M. Moniruzzaman3, N. J. Haughey3, J. W. McFadden1. 1Cornell University Ithaca, NY, 2Henan Agricultural University Zhengzhou, China, 3Johns Hopkins University Baltimore, MD.

The fungal isolate myriocin is an inhibitor of serine palmitoyltransferase and de novo ceramide (Cer) synthesis in non-ruminants. Our objectives were to determine whether myriocin suppresses de novo Cer synthesis in ruminants. Twelve mature, nonlactating crossbred ewes (49.4 � 4.90 kg) received an intravenous bolus of ethanol (CON) or 1 of 3 doses of myriocin (0.1, 0.3, or 1.0 mg/kg/BW in ethanol; LOW, MOD, or HIGH) every 48 h for 17 d. Ewes were ad libitum fed a high-energy pelleted and grass hay diet from d 1—14, and nutrient-restricted (straw only) from d 15—17. Blood was collected before morning feeding and at 0, 1, 6, and 12 h relative to bolus administration and nutrient restriction. Ewes were euthanized on d 17 for tissue collection. Plasma was analyzed for fatty acids (FA), glucose, and insulin using colorimetry and radioimmunoassay. Mass spec was used to quantify plasma Cer. As compared with CON, HIGH dose decreased metabolizable energy intake (−54%), BW and plasma insulin (P < 0.05). These effects were not observed for LOW or MOD. HIGH also increased plasma FA, relative to CON (P < 0.05). HIGH decreased plasma total, total dihydro- (DH), C20:0-, C22:0-, C24:0-, C26:0-, C22:0-DH, and C24:0-DH Cer concentrations by d 13 (P < 0.05), relative to CON. A similar but less-pronounced result was observed with MOD but not LOW. The ability of myriocin to acutely lower plasma Cer varied by species but was most pronounced 6—24 h post injection. During nutrient restriction, FA mobilization was lower within increasing dose (P < 0.01). Nutrient restriction affected plasma ceramides differently across time, based on dose and acyl moiety. Myriocin decreased the majority of Cer and DH-Cer measured in liver, omental and mesenteric adipose, and pancreas (P < 0.05). Myriocin only decreased C18:0-, C20:0-, and C18:0-DH Cer concentrations in skeletal muscle, and C18:0-Cer in subcutaneous adipose (P < 0.05). We conclude that the intravenous delivery of 0.3 mg of myriocin/kg of BW/48 h effectively decreases circulating and tissue ceramide concentrations without modifying energy intake in ruminants.

Keywords: ceramide, myriocin, ruminant.