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Hepatic Triacylglycerol Synthesis during a Period of Fatty Liver Development in Sheep^1,2,

State University of Utrecht, the Netherlands and Michigan State University, East Lansing 48824

Abstract

Fatty liver was induced in six sheep by fasting and treatment with phloridzin and epinephrine. Treatment was associated with a rise in the concentration in serum and hepatic uptake of nonesterified fatty acid (NEFA) compared with pretreatment (P < .01). At 24 h after the start of the treatment, concentrations of serum lipoprotein in each density class were not different from baseline, but all were elevated (P < .01) by 120 h of treatment. Hepatic triacylglycerol (TG) concentration increased (P < .01) 17-fold within the first 48 h of treatment, with no additional increase during the remaining 72 h. The activity of phosphatidate phosphohydrolase (PAP) in hepatic microsomes increased (P < .01) fourfold over baseline by 48 h of treatment, then declined slightly by 120 h. The activities of diacylglycerol acyltransferase (DGAT) and glycerophosphate acyltransferase (GPAT) in hepatic microsomes increased during treatment but appeared to follow a slightly different pattern from that of PAP. Activity of GPAT was not above baseline at 48 h, but was at 120 h (P < .05); DGAT activity was increased (P < .05) twofold at 48 h, with an apparent continued increase (P < .01) to threefold over baseline by 120 h of treatment. Fatty liver appeared to develop during a period of rapid hepatic uptake of NEFA without a corresponding increase in serum lipoprotein concentrations. The activities of PAP, GPAT and DGAT, putative regulators of TG synthesis rate, all increased in liver microsomes during a period of high hepatic NEFA uptake, but that of PAP appeared to coincide most closely with the development of fatty liver.

¹ Published with the approval of the Director of the MSU Agric. Exp. Sta. as Journal Article No. 12480. The experiments were completed while Dr. Herdt was on sabbatical leave at the State Univ. of Utrecht.

² The authors acknowledge the surgical assistance of G. E. Bras and the technical assistance of Anne Hartman and Ellen Schot.

³ Dept. of Large Anim. Clin. Sci., MSU.

⁴ Dept. of Large Animal Internal Diseases, Utrecht.

⁵ Dept. of Vet. Biochem., Utrecht.