The effect of short-term exercise on plasma leptin levels in patients with anorexia nervosa.

Plasma leptin concentrations are markedly reduced in malnourished patients with anorexia nervosa (AN). Whether the long-term underweight and low-fat stores affect the leptin response to exercise remains unknown. We investigated the effect of 45-minute cycle ergometer exercise (2 W kg-1 of lean body mass [LBM]) on plasma leptin, norepinephrine (NE), glycerol, and insulin levels in 10 patients with AN and in 15 healthy age-matched women (C). Plasma leptin levels immediately and 90 minutes after the exercise bout were significantly reduced compared with basal leptin levels in both AN and C groups (P<.05). Compared with the control trial, leptin levels were significantly lower immediately and 90 minutes after exercise in the AN group (P<.05) but not in the C group. Basal and exercise-induced plasma glycerol and NE levels did not differ significantly between the groups. Basal and exercise-induced plasma insulin levels were significantly lower in the AN group compared with the C group (P<.05). In conclusion, we demonstrated that a single bout of low-intensity exercise significantly reduces plasma leptin levels in patients with AN. In healthy women, exercise had no effect on lowering leptin concentrations beyond the diurnal decrease that occurs in the absence of exercise. Neither NE nor insulin are responsible for the different response of leptin to exercise in AN.

Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo- and hyperthyroid patients: an in vivo microdialysis study.

Thyroid function plays an important role in the regulation of overall metabolic rate and lipid metabolism. However, it is uncertain whether thyroid hormones directly affect lipolysis in adipose tissue and to what extent those changes contribute to overall metabolic phenotype. Our study was designed, using the microdialysis technique, to determine basal and isoprenaline-stimulated local lipolysis and to determine local concentrations of lipolysis-regulating catecholamines in abdominal subcutaneous adipose tissue in 12 patients with hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects. Plasma norepinephrine (NE) concentrations in hypothyroid subjects were significantly higher than in the control and hyperthyroid groups. In contrast, systemic, adipose NE levels in hypothyroid patients were decreased relative to controls. Hyperthyroidism, on the other hand, resulted in four-fold higher adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose tissue was significantly attenuated in hypothyroid patients and markedly increased in hyperthyroid patients in comparison with the control group. In addition to differences in basal lipolysis, hypothyroidism resulted in attenuated, and hyperthyroidism in enhanced, lipolytic response to local stimulation with beta(1,2)-adrenergic agonist isoprenaline. These results demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly modulated by thyroid function. We suggest that thyroid hormones regulate lipolysis primarily by affecting local NE concentration and/or adrenergic postreceptor signaling.

Effects of hypo- and hyperthyroidism on noradrenergic activity and glycerol concentrations in human subcutaneous abdominal adipose tissue assessed with microdialysis.

Thyroid hormones play a major role in lipid metabolism. However, whether they directly affect lipolysis locally in the adipose tissue remains unknown. Therefore, we measured abdominal sc adipose tissue norepinephrine (NE), basal, and isoprenaline-stimulated lipolysis in 12 hypothyroid patients (HYPO), six hyperthyroid patients (HYPER), and 12 healthy controls by in vivo microdialysis. Adipose tissue NE was decreased in HYPO and increased in HYPER compared with controls (90.4 +/- 2.9 and 458.0 +/- 69.1 vs. 294.9 +/- 19.5 pmol/liter, P < 0.01). Similarly, basal lipolysis, assessed by glycerol assay, was lower in HYPO and higher in HYPER than in controls (88.2 +/- 9.9 and 566.0 +/- 42.0 vs. 214.3 +/- 5.1 micromol/liter P < 0.01). The relative magnitude of isoprenaline-induced glycerol increase was smaller in HYPO (39 +/- 19.4%, P < 0.05 vs. basal) and higher in HYPER (277 +/- 30.4%, P < 0.01) than in controls (117 +/- 5.6%, P < 0.01). The corresponding changes in NE after isoprenaline stimulation were as follows: 120 +/- 9.2% (P < 0.05), 503 +/- 113% (P < 0.01), and 267 +/- 17.2 (P < 0.01). In summary, by affecting local NE levels and adrenergic postreceptor signaling, thyroid hormones may influence the lipolysis rate in the abdominal sc adipose tissue.

Loss of meal-induced decrease in plasma ghrelin levels in patients with anorexia nervosa.

Studies have shown that ghrelin plays a major role in energy homeostasis and modulation of feeding behavior. However, little is known about the influence of food consumption on plasma ghrelin levels in humans. Therefore, we investigated responses of plasma ghrelin to food intake, meal volume and meal nutritional value in healthy volunteers and women with anorexia nervosa (AN). After overnight fasting, all subjects received either a standardized breakfast or fiber. Plasma ghrelin levels were measured before and after the meal. Fasting plasma ghrelin was significantly higher in AN patients than in controls (1,800.6 +/- 47.0 vs. 795.9 +/- 24.3 pg/ml, P < 0.001) (606.8 +/- 15.8 vs. 268.2 +/- 8.2 pmol/l, P < 0.001), and correlated negatively with percentage of body fat in both groups. Ghrelin levels markedly fell after consumption of either a standardized meal or fiber in controls, but not in anorexic women. Thus, we concluded that the acute plasma ghrelin response to food intake, which in healthy individuals is independent of meal caloric value, is impaired in women with AN. This abnormality may be part of a chronic adaptation to prolonged food restriction, which attempts to restore a normal feeding conduct by maintaining the drive to eat.