1. Quantification of the energy cost of spontaneous activity in freely moving lean and obeseZucker rats was performed at 28°C and during acute cold exposure (from 28 to 5°C).2. An open-circuit metabolic chamber was supplemented with an ultrasensitive ergometric platform equipped with six unidirectional accelerometers and with an opto-electronic device for location of the rat's centre of mass. 3. Resting and mean metabolic rates during control and cold-exposure periods were similar in both groups of rats. The 'extra thermogenesis' (ET), i.e. the difference between mean and resting metabolic rate, amounted to 1 7 + I 1 and 8 6 + 0 7 % of resting metabolic rate at 28 0C, and 39X7 + 2X9 and 34X1 + 2X9% of resting metabolic rate during cold exposure for lean and obese rats, respectively. 4. During the control period obese rats moved 3-71 + 0-61 m h-1 and lean rats 8X69 + 0 57 m h-, but during cold exposure the distance moved by obese rats increased 3X58 + 0X33-fold whereas that moved by lean rats only increased 1-40 + 0*06-fold. The external work performed during spontaneous activity seldom reached 1I0 % of the increase in metabolic rate. 5. In obese rats, weight was a good predictor of the distance covered, and cold exposure induced the same percentage increase in both distance and ET. Activity-associated thermogenesis of obese rats was the predominant thermogenic source that substituted for their atrophied brown fat thermogenesis whereas in lean rats with active brown fat these correlations were not found.

Hindlimbs of mature age obese fa/fa Zucker rats were perfused and found to be markedly insulin-resistant when compared to the hindlimbs of age-matched lean Fa/? animals. Hindlimb analysis also showed a greater content of fat and a lower content of muscle in the obese. Treatment of the obese animals for 7 days with the thiazolidinedione, BRL 49653 (3 mumol/kg/day) significantly decreased the insulin resistance of the hindlimb and significantly increased the rate of weight gain in the whole rat. However, the decreased insulin resistance due to BRL 49653 could not be accounted for by an increase in the proportion of hindlimb muscle to fat or by an increase in the hindlimb muscle mass perfused.

The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing metabolic effects and appear to control different flow routes in the constant-flow perfused rat hindlimb. In the present study the association between vascular flow route recruitment and metabolism was assessed by selective microsphere embolism of either route. Microspheres (MS, 11.9 +/- 0.1 microns, mean +/- SE diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions) and the effects on hindlimb (4.7 +/- 0.1 g muscle) oxygen uptake (VO2) and indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf muscle group assessed. MS (1.5 x 10(6)) injected during vehicle, or 5-HT infusion increased VO2 (P < 0.05) but did not affect energy status. During AII, MS decreased VO2. Change in VO2 correlated positively with CrP/Cr (r = 0.68, P < 0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS (1.5 x 10(6)) increased pressure but did not affect the flow rate. The metabolic changes resulting from 1.5 x 10(6) microspheres were intensified by a second injection of 1.5 x 10(6) microspheres but further injection (> 3.0 x 10(6) microspheres) began to inhibit flow. It is concluded that a finite number (< or = 3.0 x 10(6)) of microspheres of 11.9 microns diameter has opposite effects on VO2 depending on the vasoconstrictor present and that these effects result from the occlusion of the different vascular route accessed by each vasoconstrictor. The data support the proposal that hindlimb metabolism can be controlled by vasoconstrictors as a result of selective vascular recruitment.

Uric acid and uracil were released at constant rates (0.95 and 0.4 nmol/min per g respectively) by the perfused rat hindlimb. Noradrenaline, vasopressin or angiotensin II further increased the release of these substances 2-5-fold, coinciding with increases in both perfusion pressure (vasoconstriction) and 02 uptake. The hindlimb also released, but in lesser amounts, uridine, hypoxanthine, xanthine, inosine and guanosine, and all but hypoxanthine and guanosine were increased during intense vasoconstriction. Uric acid and uracil releases were increased by noradrenaline in a dose-dependent manner. However, the release of these substances did not fully correspond with the dose-dependent increase in 02 uptake and perfusion pressure, where changes in the latter occurred at lower doses of noradrenaline. Sciatic-nerve stimulation (skeletalmuscle contraction) did not increase the release of uracil, uric acid or uridine, but instead increased the release of inosine (7-fold) and hypoxanthine (2-fold). Since the UTP content as well as the UTP/ATP ratio are higher in smooth muscle than in skeletal niuscle, it is proposed that release of uric acid and uracil arises from increased metabolism of the respective adenosine and uridine nucleotides during intense constriction of smooth muscle.

No abstract