Inverse relationship of leucine flux and oxidation to free fatty acid availability in vivo.

Abstract

To determine the effect of fatty acid availability on leucine metabolism, 14-h fasted dogs were infused with either glycerol or triglyceride plus heparin, and 46-h fasted dogs were infused with either nicotinic acid or nicotinic acid plus triglyceride and heparin. Leucine metabolism was assessed using a simultaneous infusion of L-14,5-3H]leucine and a-[1-'4Cjketoisocaproate. Leucine, a-ketoisocaproate (KIC), and totalleucine carbon (leucine plus KIC) flux and oxidation rates were calculated at steady state. In 14-h fasted animals, infusion of triglyceride and heparin increased plasma free fatty acids (FFA) by 0.7 mM (P < 0.01) and decreased leucine (P < 0.01), total leucine carbon flux (P < 0.02), and oxidation (P < 0.05). The estimated rate of leucine utilization not accounted for by oxidation and KIC flux decreased, but the changes were not significant. During glycerol infusion, leucine and KIC flux and oxidation did not change.In 46-h fasted dogs, nicotinic acid decreased FFA by 1.0 mM (P < 0.01) and increased (P < 0.05) the rate of leucine and total leucine carbon flux, but did not affect KIC flux. Leucine oxidation increased (P < 0.01) by nearly threefold, whereas nonoxidized leucine utilization decreased. Infusion of triglyceride plus heparin together with nicotinic acid blunted some of the responses observed with nicotinic acid alone.In that changes in oxidation under steady state condition reflect changes in net leucine balance, these data suggest that FFA availability may positively affect the sparing of at least one essential amino acid and may influence whole body protein metabolism.

TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation

“…However, we cannot exclude the possibility that a resistant state to insulin and/or amino acids produced by TNF-␣ was at least partially responsible for the diminished rate of synthesis (29). Elevations in plasma FFAs have been shown to be capable of modulating protein balance in vivo (47). However, no significant alterations in plasma FFA concentrations were detected in TNF-␣-infused rats.…”

Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.

“…However, we cannot exclude that factors other than insulin deficiency per se might have been responsible for the results observed. Insulin withdrawal was associated with a significant increase in the plasma concentration ofcortisol, glucagon, FFA, ketone bodies, and essential amino acids which have been reported to affect leucine and protein metabolism (13,15,56,58,(70)(71)(72)(73)(74)(75). However, in absence of other hormonal inter-actions in vitro, insulin deficiency decreased the rate of albumin gene transcription and, conversely, insulin replacement increased it (28).…”

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats

“…The metabolic response of our obese ZDF rats is probably more similar to the fair adaptation of obese subjects to starvation: these subjects had better nitrogen preservation than lean subjects and have been shown to be able to survive longer during hunger strike [43,44]. The hypothetical 'protective effect' of obesity post-injury may be related to a possible sparing action of fat on protein metabolism [45][46][47]. In fasted obese patients, an inverse relationship has been shown between urinary nitrogen excretion and level of adiposity in both human and animal models, suggesting a protein-sparing effect of lipids [45].…”

“…These authors reported an increase in both protein turnover and leucine oxidation in the lean subjects during short-term starvation, whereas there were no significant changes in the obese subjects [45]. One elegant study [46] demonstrated an inverse relationship between leucine oxidation and NEFA levels (and NEFA oxidation) in dogs. In humans, a moderate increase in NEFA (nearly 1 mmol/l) also resulted in a 20% reduction in leucine oxidation [47].…”