Cardio-respiratory changes during the onset of head-down tilt.

BACKGROUND: During spaceflight, changes in the cardiovascular system and in pulmonary mechanics take place but no apparent impairment of respiratory function occurs. However, little is known about the first hours in microgravity. HYPOTHESIS: The changes occurring at the same time in the cardiovascular and pulmonary systems could interact and lead to a transient impairment of blood gases at the onset of microgravity. METHODS: Cardiovascular and respiratory changes were studied during 6 degrees head-down tilt (HDT), a now well-known method for simulation of microgravity. After a baseline standing position, 10 men were exposed to 4 h of 6 degrees HDT. Hemodynamic parameters were measured by thoracic electrical bioimpedance. Ventilatory parameters were studied by spirographic measurements and mass spectrometer analysis of expired gases. Arterial blood parameters were analyzed by specific electrodes. RESULTS: Immediately after tilting, stroke volume and cardiac output increased, as measured by thoracic bio-impedance, while heart rate and thoracic fluid index decreased. Blood gas analysis showed hypercapnia, acidosis and a tendency to hypoxia. These changes were related to hypoventilation shown by the decrease in minute ventilation. After usually less than 30 min, all the parameters reached a steady state. Return to the standing position provoked reverse variations with orthostatic intolerance in 4 subjects. CONCLUSION: Marked changes in both the cardiovascular and respiratory systems occur within the first minutes of HDT (i.e., transition to simulated microgravity).

Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH-deficient adults.

GH deficiency impairs lipid metabolism in adults, but little is known about the direct effect of GH on adipose tissue in humans. First, the in vitro response of fat cells to GH in five GH-deficient adults was studied; second, it was investigated whether 6-month recombinant human GH (rhGH) administration modifies this response. Biopsies of fat were obtained from the periumbilical region before and after rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of GH was assessed by glycerol release, measured by bioluminescence. Before treatment, GH induced a lipolytic activity from the adipocytes, which became significantly higher after 6 months of treatment. Thus, this study provides evidence for an intrinsic lipolytic activity of GH in GH-deficient adults and for its improvement after long term rhGH administration.

Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response.

Besides exerting its own lipolytic effect, growth hormone (GH) has been reported to potentiate the lipolytic response of adipose tissue to epinephrine. It was thought interesting to find out whether long-term recombinant human growth hormone (rhGH) administration modifies epinephrine-induced lipolysis in isolated adipocytes of GH-deficient adults. In a double-blind protocol, GH-deficient subjects received either 6 mo placebo (controls, n = 5) or 6 mo rhGH (treated, n = 5). Biopsies of fat were obtained from the periumbilical region before and after placebo or rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of epinephrine was assessed by glycerol release, measured by bioluminescence. Epinephrine-induced lipolysis was not altered by 6 mo placebo, while it was significantly increased by 6 mo rhGH. A similar response was obtained with isoproterenol, but no significant differences occurred in either group with UK 14304, an alpha 2-adrenoreceptor agonist. Thus, in GH-deficient adults, long-term rhGH administration improves the lipolytic response of isolated adipocytes to epinephrine, essentially by increasing the efficiency of the beta-adrenergic pathway.

Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.

Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells.

Lipolytic response of adipocytes to epinephrine in sedentary and exercise-trained subjects: sex-related differences.

Adipose tissue lipolytic activity is increased in endurance-trained subjects, but little is known about the mechanisms of this increase. To understand more fully the mechanisms involved and to discover whether sex-related differences exist, biopsies of fat were performed in the periumbilical region of 20 sedentary subjects (10 women (W) and 10 men (M)) and 20 trained subjects (10 W, 10 M); the in vitro response to epinephrine of the collagenase-isolated fat cells was studied. Glycerol release, chosen as an adipocyte lipolysis indicator, was measured by bioluminescence. Dose-response curves with epinephrine (alpha 2 and beta agonist), with isoproterenol (beta agonist) and epinephrine + propranolol and adenosine deaminase, were studied. Epinephrine-induced lipolysis was enhanced in trained subjects and this was due to an increased efficiency of the beta-adrenergic pathway. However, differences were found between the two sexes. In trained men, the lipolysis increase resulted from the enhancement of the beta-adrenergic pathway efficiency without any significant decrease in the alpha 2-adrenergic pathway efficiency. In trained women, the lipolysis increase was not only due to the enhancement of the beta-adrenergic pathway efficiency (which was greater than in trained men), but also to a significant decrease in the alpha 2-adrenergic pathway efficiency. Despite the decrease, the alpha 2-adrenergic pathway remained more efficient in trained women than in trained men, as was the case in sedentary subjects. It is concluded that endurance training led to better lipid mobilization and that this effect seemed greater in women than in men.

Platelet alpha 2-adrenoceptors and adrenergic adipose tissue responsiveness after moderate hypocaloric diet in obese subjects.

Platelet alpha 2-adrenoceptor number was studied in obese subjects treated by a moderate hypocaloric diet (1000-1200 kcal/day = 4200-5000 kg/day) for 21-25 days. Spontaneous lipolysis and adrenergic responsiveness of isolated subcutaneous abdominal adipocytes, collected by a biopsy procedure, were studied before and after treatment on the same subjects. The number of alpha 2-adrenoceptor binding sites (Bmax values) of the platelets was increased after the hypocaloric diet, while there was no change in the equilibrium dissociation constant. Basal lipolytic activity of the adipocytes was increased after the hypocaloric treatment, whereas neither the beta-dependent lipolytic effect of isoproterenol nor the alpha 2-dependent antilipolytic effect of epinephrine were affected. It is concluded that moderate hypocaloric diet induces an up-regulation of platelet alpha 2-adrenoceptors. No modification occurs in alpha 2- and beta-adrenergic responsiveness of the subcutaneous adipocytes. Although alpha 2-adrenergic receptor binding studies on platelets have been widely used as an index for alpha 2-adrenoceptor function in other tissues, it is suggested by this study that platelet alpha 2-adrenoceptors cannot be used for prediction of alpha 2-adrenoceptor function in adipose tissue.

Lipolytic response of fat cells to catecholamines in sedentary and exercise-trained women.

It has been shown that adipose tissue lipolytic activity is increased in endurance-trained subjects. In women, adipose tissue is extensive and it was thought interesting to confirm that endurance training increases the capacity of female adipose tissue to mobilize lipids, and moreover to more fully understand the mechanisms involved. So, biopsies of fat were obtained from the periumbilical region of 13 trained female runners (T) and 17 sedentary women (S) and the in vitro response to catecholamines of the collagenase-isolated fat cells was studied. Glycerol release, chosen as adipocyte lipolysis indicator, was measured by bioluminescence for various epinephrine and norepinephrine concentrations. In both groups, these substances provoked an increase in lipolysis, but the response was significantly higher in T. In both groups, isoproterenol increased the lipolytic activity above basal concentrations at 10(-8) M and above. Lipolytic activity in T was significantly higher (P less than 0.01) than the S control at 10(-7) M and above. Epinephrine plus propranolol decreased lipolysis in both groups, but at 10(-5) M, lipolytic activity was significantly lower in S than in T (P less than 0.05). It is concluded that in female subjects, endurance training increases the sensitivity of subcutaneous abdominal adipose tissue to the lipolytic action of catecholamines; this effect seems to be related both to a decreased efficiency of the alpha 2-adrenergic pathway and to an increased efficiency of the beta-adrenergic pathway. This latter effect seems to take place at a step beyond the receptor-adenylate cyclase system in the lipolytic cascade.

Lack of desensitization of catecholamine-induced lipolysis in fat cells from trained and sedentary women after physical exercise.

A study was designed to assess whether a period of physical exercise (100 min; 60% of maximal aerobic power), known to promote sympathetic nervous system activation, had a functional impact on human fat cell responsiveness to catecholamines and beta-agonists. The lipolytic activity of isolated sc fat cells was measured before and after a period of exercise in trained and sedentary women with a similar body mass index values [20.4 +/- 0.5 (+/- SE) and 21.3 +/- 0.5 kg/m2] and an equivalent mean fat cell volume (0.216 +/- 0.022 vs. 0.278 pm 0.026 nL). Before exercise, compared with those of sedentary women, the adipocytes of trained women had greater lipolytic responsiveness to catecholamines and beta-agonists; moreover, dibutyryl cAMP had greater lipolytic efficiency on the adipocytes of the trained women. These results suggest that the differences in responsiveness of the adipocytes from sedentary and trained women are due to functional differences at a postreceptor level of the lipolytic cascade. The lipolytic (beta-adrenergic) and antilipolytic (alpha 2-adrenergic) responses of the adipocytes from both groups did not change after the period of physical activity. These results demonstrate, whatever the physical condition of the subjects, that desensitization of beta- and alpha 2-adrenergic responsiveness does not occur after a period of intense physical activity which promotes physiological activation of the sympathetic nervous system.

Effect of physical training in humans on the response of isolated fat cells to epinephrine.

Endurance training helps muscle tissue oxidize lipids and therefore helps conserve glycogen. It was thought interesting to find out if, in addition to this preferential use of fatty acids by muscle tissue, there is an increase in the capacity of adipose tissue to mobilize lipids. So the response to epinephrine of collagenase-isolated fat cells obtained after biopsies of fat performed in the periumbilical region of 10 trained marathon runners (T) and 10 sedentary subjects (S), all males, was studied in vitro. Glycerol release, chosen as adipocyte lipolysis indicator, was measured by bioluminescence. Lipolysis was studied with increased epinephrine concentration. This caused a significant increase in lipolysis only in the T subjects. The dose-response curves were significantly different for T and S subjects at 10(-6) M and above (P less than 0.05). To determine the modification mechanisms observed, lipolysis with isoproterenol and epinephrine plus propranolol were studied. Isoproterenol significantly increased lipolysis in both groups. The dose-response curves were significantly different at 10(-7) M (P less than 0.01) and above. In both groups, epinephrine plus propranolol significantly decreased lipolysis without distinction between T and S. It is concluded that in male subjects endurance training increases the sensitivity of subcutaneous abdominal adipose tissue to the lipolytic action of epinephrine; this effect seems to be related to an increased response of the beta-adrenergic pathways.