What Constitutes a Gluconeogenic Precursor?

A gluconeogenic precursor is a biochemical compound acted on by a gluconeogenic pathway enabling the net synthesis of glucose. Recognized gluconeogenic precursors in fasting placental mammals include glycerol, lactate/pyruvate, certain amino acids, and odd-chain length fatty acids. Each of these precursors is capable of contributing net amounts of carbon to glucose synthesis via the tricarboxylic acid cycle (TCA cycle) because they are anaplerotic, that is, they are able to increase the pools of TCA cycle intermediates by the contribution of more carbon than is lost via carbon dioxide. The net synthesis of glucose from even-chain length fatty acids (ECFAs) in fasting placental mammals, via the TCA cycle alone, is not possible because equal amounts of carbon are lost via carbon dioxide as is contributed from fatty acid oxidation via acetyl-CoA. Therefore, ECFAs do not meet the criteria to be recognized as a gluconeogenic precursor via the TCA cycle alone. ECFAs are gluconeogenic precursors in organisms with a functioning glyoxylate cycle, which enables the net contribution of carbon to the intermediates of the TCA cycle from ECFAs and the net synthesis of glucose. The net conversion of ECFAs to glucose in fasting placental mammals via C3 metabolism of acetone may be a competent though inefficient metabolic path by which ECFA could be considered a gluconeogenic precursor. Defining a substrate as a gluconeogenic precursor requires careful articulation of the definition, organism, and physiologic conditions under consideration.

Octanoate and nonaoate oxidation increases 50-80% over the first two days of life in piglet triceps brachii and gracilis muscle strips.

An in vitro muscle strip incubation system was developed to measure the rate of catabolism of 1 mmol/L [1-(14)C]octanoate, 1 mmol/L [1-(14)C]nonanoate, 1 mmol/L [9-(14)C]nonanoate, and 10 mmol/L [U-(14)C]glucose by measuring the recovery of (14)CO(2). Muscle strips (13 mm × 1.5 mm, ~50 mg) were isolated from triceps brachii and gracilis muscles of newborn and 2-d-old, small (<950 g) and large (>1450 g) piglets. The position of the (14)C label in the substrate affected the rate and amount of recovery in (14)CO(2). Therefore, comparisons were made between age groups (0 vs. 2 d old) within substrates but limited across substrates to comparisons of [1-(14)C]-labeled fatty acids. The medium-chain fatty acid (MCFA) oxidation rates [pmol/(h · mg)] in muscle strips isolated from piglets from the 2 weight groups (<950 and >1450 g) did not differ (P > 0.99), there was a trend towards a difference between triceps brachii and gracilis muscle (P = 0.09; data not shown), and there were no significant interactions involving pig weight or muscle type; therefore, results were pooled across these factors. During the first 2 d of life, MCFA oxidation [pmol/(h • · mg muscle strip)] increased (P < 0.05) 50-80%, but the glucose oxidation rate did not change (P > 0.82). By d 2, the oxidation rate of nonanoate as represented by the one carbon was 25% greater than for octanoate (P < 0.05). The conversion of [9-(14)C]nonanoate to (14)CO(2) indicated that muscle had the capacity to oxidize the propionyl-CoA produced by ß-oxidation of nonanoate and that odd-chain C-9 MCFA provided anabolic carbon to the citric acid cycle.

Blood D-(-)-3-hydroxybutyrate concentrations after oral administration of trioctanoin, trinonanoin, or tridecanoin to newborn rhesus monkeys (Macaca mulatta).

Premature newborn infants are born with limited stores of glycogen and fat. Energy, such as medium-chain triglycerides (MCT), which can spare the use of body protein as metabolic energy, may be beneficial. This study compares MCT containing C8, C9, or C10 fatty acids as oral sources of energy for newborn rhesus monkeys (Macaca mulatta). On day 1 of life, 4 groups of 5 monkeys were given a single dose of water or MCT by nasogastric tube. The dose provided approximately 80% of the expected energy requirement. Plasma C8:0, C9:0, and C10:0 fatty acids and whole-blood D-(-)-3-hydroxybutyrate (3HB) concentrations were measured at 0, 1, and 3 h after dosing. Concentrations of free fatty acids (C8, C9, or C10) and ketone (3HB) increased with time after the dose. At 1 and 3 h, concentrations of C8 and C9 did not differ, but C9 was greater than C10. At 1 h, blood 3HB concentrations due to C8 triglyceride were higher than C9 or C10 (503 versus 174 and 225 µmol/L respectively). As MCT chain length increased from C8 to C10, blood concentration of 3HB decreased. Odd-chain MCT (C9 versus C8) resulted in lower whole-blood ketone (3HB), perhaps due to C9 metabolism or the rate of release or uptake of fatty acids. These results have implications for the use of MCT in nutritional supplements for preterm infants.

Effects of caloric restriction and a moderate or intense physiotherapy program for treatment of lameness in overweight dogs with osteoarthritis.

OBJECTIVE: To evaluate the effects of a weight reduction program combined with a basic or more complex physical therapy program including transcutaneous electric nerve stimulation on lameness in overweight dogs with osteoarthritis. DESIGN: Nonblinded prospective randomized clinical trial. Animals-29 adult overweight or obese dogs with a body condition score of 4/5 or 5/5 and clinical and radiographic signs of osteoarthritis. PROCEDURES: A weight-loss program was initiated for all dogs. One group received caloric restriction and a home-based physical therapy program. The other group received the identical dietetic protocol and an intensive physical therapy program including transcutaneous electrical nerve stimulation. Lameness was assessed clinically and by kinetic gait analysis on a treadmill with 4 force plates to measure symmetry of ground reaction forces (GRFs) of the affected and contralateral limbs in bimonthly intervals for 6 months. RESULTS: Significant weight loss was achieved in both groups; however, greater weight reduction was attained by dogs treated with caloric restriction and intensive physiotherapy. Mobility and symmetry indices of GRFs were improved after 6 months; the best outcome was detected in the group receiving energy restriction combined with intensive physical therapy. CONCLUSIONS AND CLINICAL RELEVANCE: Caloric restriction combined with intensive physical therapy improved mobility and facilitated weight loss in overweight dogs. The combination of dietetic and physical therapy may help to improve the health status more efficiently than dietetic treatment alone.