Energy restriction effects on splanchnic and peripherial tissue metabolite fluxes with or without the addition of Lasalocid

Concentration and net fluxes of glucose (GLU), nonesterifled fatty acids (NEFA), acetoacetate (ACAC), β-hydroxybutyrate (BOHB) and volatile fatty acids (VFA) were studied in mature, non-pregnant, non-lactating ewes with or without the addition of the ionophore Lasalocid. Chronic indwelling catheters were placed in portal, hepatic and mesenteric veins, and the caudal vena cava and aorta at least 14 days prior to experiments. Ewes were fed alfalfa pellets at 100% or 50% of the NRC metabolizable energy requirement during the first study. During the second study, the feeding regimen was identical except for the addition of Lasalocid (44 mg/kg) to the fed. On experiment days, paraaminohippurate (PAH, 1.5% @ .764 ml/min.) was infused via the mesenteric catheter in order to measure blood flow across down stream tissues. After a one hour equilibration period, a series of 6 samples (12 ml) were drawn simultaneously at 30 min. intervals from the portal and hepatic veins and the caudal vena cava and aorta. Flux rates were calculated by multiplying venoarterial (V-A) differences by blood flow rates across the respective tissue. Rump V-A differences were calculated instead of flux rates because a simultaneous blood flow could not be measured. Whole blood was analyzed for PAH, GLU, ACAC and BOHB. Plasma was analyzed for NEFA and VFA’s.

During the first study, energy restriction (ER) reduced splanchnic blood flow specifically at the expense of the portal vein contribution to the liver (HEP) indicating that a larger percentage of peripherally released metabolites reached the liver. Energy restriction also decreased (P < .05) arterial glucose from 2.68 to 2.41 mM due to increased (P < .05) glucose uptake by portal- drained viscera (PDV). Liver GLU release (30 mmol/h) was unchanged. NEFA arterial concentrations increased (P < .01) 2 fold due to a 3 fold increase (P < .01) in rump release and despite a 2.5 fold increase (P < .01) in hepatic uptake. Hepatic extraction of NEFA also increased (P < .01) by 50%. Because HEP NEFA uptake increased during ER, HEP release of ACAC decreased (P < .01), while release of BOHB increased (P < .05) 2 fold. However, PDV release of both ketones decreased ~60% (P < .05, ACAC; P < .05, BOHB) due to the energy restriction. Arterial acetate concentration decreased (P < .01) during ER by 36% due to a decrease (P < .01) in PDV release of ~50% (927 to 439 μmol/min). There was no significant HEP flux of acetate, but rump uptake decreased (P < .01) 43%, dependent upon concentration. Arterial propionate concentration was unaffected by ER despite a decrease (P < .01) of 60% in PDV release due to a concomitant decrease (P < .01) of 60% in HEP uptake. Rump uptake of propionate was not affected by ER, remaining constant at ~25-35% of circulating concentrations. Arterial butyrate concentrations statistically decreased (P < .01) from 8 to 5 μM with ER, with ER, however, this may not be physiologically significant because both PDV release and HEP uptake decreased (P < .01) resulting in no change in total splanchnic output. This work demonstrates that decreasing ME intake by 50% increases the animals reliance on endogenous fuels (i.e. hepatic ketogenesis and peripheral lypolysis) because potential ME from VFA PDV release decreased probably due to decreased organic matter fermentation.

During the second study, energy restriction did not change splanchnic blood flow. Arterial glucose concentration actually increased (P < .01) from 2.36 to 2.56mM despite a decease (P < .05) in total splanchnic release of 40%. Liver release of GLU was not statistically different, however, it was approx. 33% lower than what was expected (20 vs. 30 mmol/h). NEFA arterial concentrations increased (P < .01) 2 fold despite a 2 fold increase (P < .01) in hepatic uptake and a switch from rump release to utilization (P < .01). Arterial ACAC concentrations did not change despite a decrease (P < .01) of 60% in portal vein viscera (PDV) release. BOHB arterial concentrations increased (P < .01) due to an increase (P < .01) in HEP production of 45%. Acetate arterial concentrations decreased (P < .01), as did portal concentrations. PDV acetate release decreased (P < .01) almost 65%, resulting in decreased (P < .01) TSP release. Propionate arterial concentrations decreased (P < .01) almost 50%, while portal concentrations decreased (P < .01) almost 65%. PDV release of propionate decreased almost 75%. HEP propionate uptake decreased nearly 70%. However, TSP release still saw a decrease (P < .01) from 31 to 2 μmol/min. Butyrate arterial concentrations decreased (P < .01), as did portal concentrations. There was no change in TSP butyrate release, despite a decrease (P < .01) of 65% in PDV release. HEP butyrate uptake also decreased (P < .01) 66%. Valerate portal concentrations decreased (P<.05) 40%. PDV release of valerate decreased (P < .05) 40%, as did HEP uptake. There were no significant net flux changes with either of the branched chain volatile fatty acids, isobutyrate and isovalerate.