The FTO variant that confers a predisposition to obesity does not appear to be involved in the regulation of energy expenditure but may have a role in the control of food intake and food choice, suggesting a link to a hyperphagic phenotype or a preference for energy-dense foods.

We confirm our previous findings that MPS responses to AAs are transient, even with oral protein bolus. However, changes in MPS only reflect elevated mTORC1 signaling during the upswing in MPS.

The ability of insulin to promote the phosphorylation of some proteins and the dephosphorylation of others is paradoxical. An insulin-stimulated protein kinase is shown to activate the type-1 protein phosphatase that controls glycogen metabolism, by phosphorylating its regulatory subunit at a specific serine. Furthermore, the phosphorylation of this residue is stimulated by insulin in vivo. Increased and decreased phosphorylation of proteins by insulin can therefore be explained through the same basic underlying mechanism.

SUMMARY Since its first documented observation in exhausted animal muscle in the early 19th century, the role of lactate (lactic acid) has fascinated muscle physiologists and biochemists. Initial interpretation was that lactate appeared as a waste product and was responsible in some way for exhaustion during exercise. Recent evidence, and new lines of investigation, now place lactate as an active metabolite, capable of moving between cells, tissues and organs, where it may be oxidised as a fuel or reconverted to form pyruvate or glucose. The questions now to be asked concern the effects of lactate at the systemic and cellular level on metabolic processes. Does lactate act as a metabolic signal to specific tissues, becoming a metabolite pseudo-hormone?Does lactate have a role in whole-body coordination of sympathetic/parasympathetic nerve system control? And, finally, does lactate play a role in maintaining muscle excitability during intense muscle contraction? The concept of lactate acting as a signalling compound is a relatively new hypothesis stemming from a combination of comparative, cell and whole-organism investigations. It has been clearly demonstrated that lactate is capable of entering cells via the monocarboxylate transporter (MCT) protein shuttle system and that conversion of lactate to and from pyruvate is governed by specific lactate dehydrogenase isoforms, thereby forming a highly adaptable metabolic intermediate system. This review is structured in three sections,the first covering pertinent topics in lactate's history that led to the model of lactate as a waste product. The second section will discuss the potential of lactate as a signalling compound, and the third section will identify ways in which such a hypothesis might be investigated. In examining the history of lactate research, it appears that periods have occurred when advances in scientific techniques allowed investigation of this metabolite to expand. Similar to developments made first in the 1920s and then in the 1980s, contemporary advances in stable isotope, gene microarray and RNA interference technologies may allow the next stage of understanding of the role of this compound, so that, finally, the fundamental questions of lactate's role in whole-body and localised muscle function may be answered.

We used three techniques of precooling to test the hypothesis that heat strain would be alleviated, muscle temperature (Tmu) would be reduced, and as a result there would be delayed decrements in peak power output (PPO) during exercise in hot, humid conditions. Twelve male team-sport players completed four cycling intermittent sprint protocols (CISP). Each CISP consisted of twenty 2-min periods, each including 10 s of passive rest, 5 s of maximal sprint against a resistance of 7.5% body mass, and 105 s of active recovery. The CISP, preceded by 20 min of no cooling (Control), precooling via an ice vest (Vest), cold water immersion (Water), and ice packs covering the upper legs (Packs), was performed in hot, humid conditions (mean +/- SE; 33.7 +/- 0.3 degrees C, 51.6 +/- 2.2% relative humidity) in a randomized order. The rate of heat strain increase during the CISP was faster in Control than Water and Packs (P < 0.01), but it was similar to Vest. Packs and Water blunted the rise of Tmu until minute 16 and for the duration of the CISP (40 min), respectively (P < 0.01). Reductions in PPO occurred from minute 32 onward in Control, and an increase in PPO by approximately 4% due to Packs was observed (main effect; P < 0.05). The method of precooling determined the extent to which heat strain was reduced during intermittent sprint cycling, with leg precooling offering the greater ergogenic effect on PPO than either upper body or whole body cooling.

Insulin stimulated protein kinase Ba (PKBa) more than 10-fold and decreased glycogen synthase kinase-3 (GSK3) activity by 50 ± 10% in skeletal muscle and adipocytes. Rapamycin did not prevent the activation of PKB, inhibition of GSK3 or stimulation of glycogen synthase up to 5 min. Thus rapamycin-insensitive pathways mediate the acute effect of insulin on glycogen synthase in the major insulin-responsive tissues. The small and very transient effects of EGF on phosphatidylinositol (3,4,5)P 3 PKBa and GSK3 in adipocytes, compared to the strong and sustained effects of insulin, explains why EGF does not stimulate glucose uptake or glycogen synthesis in adipocytes.

Quadriceps muscle protein turnover was assessed in the post-absorptive state in six men immediately after the end of unilateral leg immobilization (37 +/- 4 days) in a plaster cast after tibial fracture. A primed-constant intravenous infusion of L-[1-13C]leucine was administered over 7 h. Quadriceps needle biopsies, taken bilaterally at the end of the infusion, were analysed for muscle protein leucine enrichment with 13C. Quadriceps muscle protein synthetic rate, calculated from the fractional incorporation of [13C]leucine into protein compared with the average enrichment of blood alpha-ketoisocaproate, was 0.046 +/- 0.012%/h in the uninjured leg, but was only 0.034 +/- 0.007%/h in the quadriceps of the previously fractured leg (P less than 0.05, means +/- SD). Muscle RNA activity (i.e. protein synthetic rate per RNA) fell from 0.27 +/- 0.08 microgram of protein synthesized h-1 microgram-1 of RNA in the control leg to 0.14 +/- 0.03 microgram of protein synthesized h-1 microgram-1 of RNA in the immobilized leg (P less than 0.02). Immobilization was associated with a significant atrophy of type I muscle fibres (mean diameter 69.5 +/- 21 microns immobilized, 81.1 +/- 18 microns control, P less than 0.05), but no significant change occurred in type II fibre diameter. Mean quadriceps fibre volume calculated from the values for fibre diameter and percentage of each fibre type, was smaller in the injured leg by 10.6%; this value was near to the calculated difference in muscle thigh volume (calculated from thigh circumference and skin-fold thickness) which was less by 8.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate why flooding methods give higher rates than constant-infusion methods for muscle protein synthesis, we studied seven healthy postabsorptive male volunteers (20-42 yr; 67-74 kg) during a 7.5-h primed constant infusion of L-[1-13C]valine (99 atoms %, 1.5 mg/kg prime, 1.5 mg.kg-1.h-1); at 6.5 h they were given a flood of L-[1-13C]leucine (20 atoms %, 0.05 g/kg). Musculus tibialis anterior biopsies were taken at 0.5, 6, and 7.5 h, and blood was sampled as appropriate. The enrichment of valine and leucine in muscle protein (isotope ratio mass spectrometry of protein amino acid-derived 13CO2) was compared with the average enrichment of various amino acid pools (gas chromatography-mass spectrometry). During infusion of [13C] valine the rate of muscle protein synthesis measured using alpha-ketoisovalerate (alpha-KIV) as precursor surrogate was 0.043 +/- 0.002%/h (SE). After flooding with leucine, the incorporation rate of [13C]valine increased by 70% (P less than 0.05), i.e., apparent muscle protein synthetic rate (based on alpha-[13C]KIV) increased to 0.065 +/- 0.009%/h (P less than 0.05); the rate calculated from the [13C]leucine flood was 0.060 +/- 0.005%/h (P less than 0.01). The synthetic rates calculated using the constant-infusion method were higher after flooding, irrespective of the precursor chosen, raising serious concern about the validity of the flooding-dose method.