Acipimox Administration With Exercise Induces a Co-feedback Action of the GH, PP, and PYY on Ghrelin Associated With a Reduction of Peripheral Lipolysis in Bulimic and Healthy-Weight Czech Women: A Randomized Study.

Objective: Anti-lipolytic drugs and exercise are enhancers of growth hormone (GH) secretion. Decreased circulating free fatty acids (FFA) have been proposed to exert ghrelin-GH feedback loop after administration of an anti-lipolytic longer-acting analog of nicotinic acid, Acipimox (OLB, 5-Methylpyrazine-2-carboxylic acid 4-oxide, molecular weight of 154.1 Da). OLB administration strongly suppresses plasma FFA during exercise. Neuroendocrine perturbations of the adipose tissue (AT), gut, and brain peptides may be involved in the etiopathogenesis of eating disorders including bulimia nervosa (BN) and anorexia nervosa. BN is characterized by binge eating, self-induced vomiting or excessive exercise. Approach: To test the hypothesis that treatment with OLB together with exercise vs. exercise alone would induce feedback action of GH, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), and leptin on ghrelin in Czech women with BN and in healthy-weight Czech women (HW). The lipolysis rate (as glycerol release) in subcutaneous abdominal AT was assessed with microdialysis. At an academic medical center, 12 BN and 12 HW (the control group) were randomized to OLB 500 mg 1 h before a single exercise bout (45 min, 2 W/kg of lean body mass [LBM]) once a week vs. identical placebo over a total of 2 weeks. Blood plasma concentrations of GH, PP, PYY, leptin, ghrelin, FFA, glycerol, and concentrations of AT interstitial glycerol were estimated during the test by RIA utilizing 125I-labeled tracer, the electrochemiluminescence technique (ECLIA) or colorimetric kits. Results: OLB administration together with short-term exercise significantly increased plasma GH (P < 0.0001), PP (P < 0.0001), PYY, and leptin concentrations and significantly decreased plasma ghrelin (P < 0.01) concentrations in both groups, whereas short-term exercise with placebo resulted in plasma ghrelin (P < 0.05) decrease exclusively in BN. OLB administration together with short-term exercise significantly lowered local subcutaneous abdominal AT interstitial glycerol (P < 0.0001) to a greater extent in BN. Conclusion: OLB-induced suppression of plasma ghrelin concentrations together with short-term exercise and after the post-exercise recovering phase suggests a potential negative co-feedback of GH, PP, PYY, and leptin on ghrelin secretion to a greater extent in BN. Simultaneously, the exercise-induced elevation in AT interstitial glycerol leading to a higher inhibition of peripheral lipolysis by OLB in BN. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03338387.

The role of "mixed" orexigenic and anorexigenic signals and autoantibodies reacting with appetite-regulating neuropeptides and peptides of the adipose tissue-gut-brain axis: relevance to food intake and nutritional status in patients with anorexia nervosa and bulimia nervosa.

Eating disorders such as anorexia (AN) and bulimia nervosa (BN) are characterized by abnormal eating behavior. The essential aspect of AN is that the individual refuses to maintain a minimal normal body weight. The main features of BN are binge eating and inappropriate compensatory methods to prevent weight gain. The gut-brain-adipose tissue (AT) peptides and neutralizing autoantibodies play an important role in the regulation of eating behavior and growth hormone release. The mechanisms for controlling food intake involve an interplay between gut, brain, and AT. Parasympathetic, sympathetic, and serotoninergic systems are required for communication between brain satiety centre, gut, and AT. These neuronal circuits include neuropeptides ghrelin, neuropeptide Y (NPY), peptide YY (PYY), cholecystokinin (CCK), leptin, putative anorexigen obestatin, monoamines dopamine, norepinephrine (NE), serotonin, and neutralizing autoantibodies. This extensive and detailed report reviews data that demonstrate that hunger-satiety signals play an important role in the pathogenesis of eating disorders. Neuroendocrine dysregulations of the AT-gut-brain axis peptides and neutralizing autoantibodies may result in AN and BN. The circulating autoantibodies can be purified and used as pharmacological tools in AN and BN. Further research is required to investigate the orexigenic/anorexigenic synthetic analogs and monoclonal antibodies for potential treatment of eating disorders in clinical practice.

Lifestyle intervention discloses an association of the Eating Inventory-51 factors with cardiometabolic health risks.

Factors of the Eating Inventory-51 (EI) were revealed as significant predictors of health risks. Associations of EI factors (restraint, disinhibition, hunger) with cardiometabolic risk parameters and selected hormones were analysed before and after an in-patient weight reduction programme. Sixty-seven women (age: 48.7 ± 12.2 years; body mass index: 32.4 ± 4.4 kg/m(2)), who exhibited stable weight on a 7 MJ/day diet during the first week, obtained a 4.5 MJ/day diet over the subsequent 3-week period. No significant relations were observed before the weight reduction. After weight loss, restraint score negatively correlated with total cholesterol, fasting blood glucose, C peptide, insulin and neuropeptide Y. Hunger score was positively related to insulin and neuropeptide Y. Disinhibition score correlated positively with lipid profile and neuropeptide Y, while negatively with adiponectin. An implementation of a standard dietary and lifestyle pattern for 3 weeks revealed significant associations between EI factors and metabolic risks in women.

Short-term exercise combined with Acipimox administration induces an increase in plasma ACTH and its subsequent fall in the recovery phase in bulimic women.

OBJECTIVE: Free fatty acids (FFA)-adrenocorticotropin (ACTH) feedback loop between adipose tissue and the hypothalamic-pituitary centers in the brain has been suggested to be affected by the exercise and by administration of anti-lipolytic drugs. Also leptin may be affected by exercise. Dysfunction of FFA-leptin-ACTH secretion might be involved in binge eating and subsequent purging as is the case in bulimia nervosa (BN). METHODS: In the present single-blind, randomized study, we explored responses of plasma ACTH, leptin and FFA concentrations to exercise (45 min, 2 W/kg of lean body mass [LBM]) with Acipimox (Aci), an anti-lipolytic nicotinic acid analog, or placebo randomly received in nine women with BN and nine healthy women. RESULTS: The exercise with Aci administration resulted in plasma ACTH (p<0.001) and leptin increase higher in BN patients and a decrease in the plasma FFA levels in both groups. The falling of plasma ACTH (p<0.01) levels in the post-exercise recovering phase (90-minute) with Aci administration is more expressed in BN patients. The exercise induced an increase in plasma ACTH (p<0.05) and FFA levels and a decrease in the plasma leptin level in both groups. CONCLUSIONS: We demonstrated that the Aci-induced elevation in plasma ACTH (p<0.001) levels after the exercise higher in BN patients and that the falling of plasma ACTH (p<0.01) levels in the post-exercise recovering phase (90-minute) with Aci administration is suppressed only in BN patients, while Aci increased plasma leptin levels in this recovering phase more in BN patients. Therefore, these observations led us to suggesting that FFA-leptin-ACTH are involved in the dysregulation of neuroendocrine profile in this syndrome and that Aci affects a FFA-independent mechanism. In conclusion, Aci can be considered acceptable in the treatment of eating disorders, and it may also serve as an alternative low-dose dexamethasone suppression test (LDDST) in these patients. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000309886.

Comparison of a high-carbohydrate and high-protein breakfast effect on plasma ghrelin, obestatin, NPY and PYY levels in women with anorexia and bulimia nervosa.

BACKGROUND: The present study investigated plasma levels of gut-brain axis peptides ghrelin, obestatin, NPY and PYY after consumption of a high-carbohydrate (HC) and high-protein (HP) breakfast in patients with anorexia nervosa, bulimia nervosa and in healthy controls. These peptides play an important role in regulation of energy homeostasis and their secretion is disturbed under condition of eating disorders. As various types of consumed macronutrients may induce different plasma hormone responses, so we examined these responses in women patients with eating disorders and compared them with those of healthy controls. METHODS: We examined plasma hormone responses to HC and HP breakfast in patients with AN (n = 14; age: 24.6 ± 1.8 years, BMI: 15.3 ± 0.7), BN (n = 15; age: 23.2 ± 1.7 years, BMI: 20.5 ± 0.9) and healthy controls (n = 14; age: 24.9 ± 1.4 years, BMI: 21.1 ± 0.8). Blood samples were drawn from the cubital vein, the first blood drawn was collected before meal, and then 30, 60, 90, 120 and 150 min after breakfast consumption. Plasma hormone levels were determined by commercially available RIA kits. RESULTS: Fasting and postprandial plasma obestatin levels were significantly increased in both AN and BN patients, while plasma ghrelin levels were significantly increased in AN patients only. After breakfast consumption, plasma levels of ghrelin and obestatin decreased, although they were still above the range of values of healthy controls. Fasting NPY plasma levels were significantly increased in AN and BN patients and did not change postprandially. Fasting PYY levels were comparable in AN, BN and healthy controls, but postprandially significantly increased after HP breakfast in AN and BN patients. Different reactions to breakfast consumption was found for ghrelin and PYY among investigated groups, while for obestatin and NPY these reactions were similar in all groups. CONCLUSIONS: Significant increase of obestatin and NPY in AN and BN patients may indicate their important role as the markers of eating disorders. Different reactions of ghrelin and PYY to breakfast consumption among groups suggest that role of these hormones in regulation of energy homeostasis can be adjusted in dependence to acute status of eating disorder.

The role of sympathetic nervous system in the development of neurogenic pulmonary edema in spinal cord-injured rats.

The pronounced activation of sympathetic nervous system is a necessary prerequisite for the development of neurogenic pulmonary edema (NPE) in rats with balloon compression of spinal cord. In this study we examined whether this is a consequence of rapid activation of spinal pathways leading to sympathetic venoconstriction, blood pressure rise, and reflex bradycardia. We found that NPE development can be prevented by epidural upper thoracic anesthesia or by transection of the upper spinal cord. This indicates an important role of spinal pathways activation. NPE development can also be prevented by moderate blood loss, supporting the role of blood redistribution to pulmonary circulation. In rats developing NPE the catecholamine surge following spinal cord compression involved not only a dramatic increase of circulating norepinephrine but also of epinephrine levels. The pretreatment of rats with α-1 adrenoceptor blocker prazosin, α-2 adrenoceptor blocker yohimbine, or calcium channel blocker nifedipine prevented NPE development, whereas the effect of ß-adrenoceptor blockade with propranolol was less convincing. In conclusion, considerable activation of thoracic spinal pathways, followed by marked catecholamine secretion, play a major role in the development of NPE in spinal cord-injured rats. Enhanced α-adrenergic nifedipine-sensitive vasoconstriction is responsible for observed blood pressure changes, subsequent baroreflex bradycardia, and blood volume redistribution, which represent major pathogenetic mechanisms of NPE development.

A higher response of plasma neuropeptide Y, growth hormone, leptin levels and extracellular glycerol levels in subcutaneous abdominal adipose tissue to Acipimox during exercise in patients with bulimia nervosa: single-blind, randomized, microdialysis study.

BACKGROUND: Neuropeptide Y (NPY) is an important central orexigenic hormone predominantly produced by the hypothalamus, and recently found to be secreted in adipose tissue (AT). Acipimox (Aci) inhibits lipolysis in AT and reduces plasma glycerol and free fatty acid (FFA) levels. Exercise and Aci are enhancers of growth hormone (GH) and NPY secretion and exercise may alter leptin levels. We expect to find abnormal neuropeptidergic response in plasma and AT in patients with bulimia nervosa (BN). We hypothesize that Aci influences these peptides via a FFA-independent mechanism and that Aci inhibits lipolysis through a cyclic adenosine monophosphate (cAMP)-dependent pathway. Dysregulations of the AT-brain axis peptides might be involved in binge eating as is the case in BN. METHODS: The objective of this study was to determine the responses of plasma NPY, GH, leptin, FFA and glycerol levels to exercise in BN patients and healthy women (C) given the anti-lipolytic drug Aci or placebo. The secondary objective of this study was to compare the responses of extracellular glycerol levels and plasma glycerol levels to exercise alone or together with Aci administration in BN patients and C women. Extracellular glycerol was measured in vivo in subcutaneous (sc) abdominal AT using microdialysis. Eight BN and eight C women were recruited for this single-blind, randomized study. Aci or placebo was given 1 hour before the exercise (45 min, 2 W/kg of lean body mass [LBM]). NPY, GH, leptin, FFA, glycerol plasma and AT glycerol levels were measured using commercial kits. RESULTS: The primary outcome of this study was that the exercise with Aci administration resulted in plasma NPY and GH increase (after a 45-minute exercise) and leptin (after a 90-minute post-exercise recovering phase) increased more in BN patients. The secondary outcomes of this study were that the exercise with Aci administration induced a higher decrease of extracellular glycerol in BN patients compared to the C group, while the exercise induced a higher increase of glycerol concentrations in sc abdominal AT of BN patients. Plasma glycerol levels decreased more in BN patients and plasma FFA levels were depressed in both groups after the exercise with Aci administration. The exercise induced similar increases in plasma NPY, GH, FFA and glycerol levels, and a similar decrease in the plasma leptin level in both groups. CONCLUSIONS: We confirm the results of a single-blind, randomized, microdialysis study, i.e. that the Aci-induced elevation in plasma NPY and GH levels during the exercise is higher in BN patients and that Aci increased plasma leptin levels in the post-exercise recovering phase (90-minute) more in BN patients. The post-exercise rise (45-minute) in AT glycerol is much more attenuated by acute Aci treatment in BN patients. Simultaneously, we found facilitated turnover of plasma glycerol after the exercise together with Aci administration in BN. Our results support the hypotheses that Aci exerts an effect on the FFA-independent and cAMP-dependent mechanism. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000955910.

Changes of orexin A plasma levels in girls with anorexia nervosa during eight weeks of realimentation.

OBJECTIVE: Orexin A (OXA) is a hypothalamic neuropeptide involved in regulation of food intake and nutritional status. There are multiple disturbances of neuropeptide signaling described in girls with anorexia nervosa (AN), but OXA levels have not been addressed in this population to date. Therefore, we analyzed OXA levels of AN girls in this study. METHOD: OXA (radioimmunoassay/RIA/method), leptin, insulinlike growth factor-1 (IGF-1), and insulinlike growth factor-1 binding protein-3 (IGFBP-3) levels were measured before and after 8 weeks of realimentation in 36 girls with AN and in 14 healthy controls (control group: CG). RESULTS: Average weight increased significantly in AN during the study (p < .0001), while plasma levels of OXA decreased (before realimentation: 56.2 ± 2.4 pg/ml; after realimentation: 47.5 ± 1.4 pg/ml; p = .0025). OXA levels before realimentation differed from levels in the CG (47.15 ± 2.6 pg/ml, p = .034), but not afterward. We did not find any correlation between OXA and age, height, weight, BMI; or IGF-1, IGFBP-3, and leptin levels. DISCUSSION: OXA levels in untreated AN patients differ significantly from healthy subjects and decrease during realimentation. These findings indicate that OXA may be involved in the nutritional regulation of malnourished children and adolescents.

Acipimox during exercise points to an inhibitory feedback of GH on ghrelin secretion in bulimic and healthy women.

OBJECTIVE: Ghrelin is predominantly produced by the stomach and the growth hormone (GH)-ghrelin feedback loop between the stomach and the pituitary gland has recently been suggested. The disruption of the gut-brain axis might be involved in bulimia nervosa (BN). METHODS: We investigated responses of plasma GH, ghrelin, and neuropeptide Y (NPY) concentrations to exercise or to exercise after the administration of the antilipolytic drug Acipimox (Aci) in seven BN patients and seven healthy women (C). Aci was administered 1h before exercise (45 min, 2 W/kg of lean body mass/LBM/). Ghrelin, GH, NPY, free fatty acids (FFA) and glycerol plasma levels were measured during the test using commercial kits. RESULTS: The exercise induced an increase in plasma GH, NPY and FFA in both groups and a decrease in plasma ghrelin levels only in BN patients. Exercise after Aci administration resulted in an increase in plasma GH, and a decrease in plasma ghrelin in both groups; NPY increased more in BN patients. Exercise-induced FFA increase was depressed after Aci. CONCLUSIONS: We conclude that the Aci-induced suppression in plasma ghrelin levels during exercise in both groups suggests a negative feedback of GH on ghrelin secretion. Observed changes in plasma FFA levels were not related to changes in GH and ghrelin levels.

[Changes of plasma obestatin and ghrelin levels after soluble fiber with glucose and after fiber alone in healthy women and in patients with bulimia nervosa]. / Zmeny plazmatických hladin obestatinu a ghrelinu po podání rozpustné vlákniny s glukózou a samotné vlákniny zdravým zenám a pacientkám s bulimia nervosa.

BACKGROUND: The recent identification of obestatin, a novel peptide hormone derived from the same gene as ghrelin, has added further complexity to ghrelin physiology. Despite the rapid progress, many questions remain unanswered, including the regulation of orexigen ghrelin and putative anorexigen obestatin secretion by food composition in humans. The present study was undertaken to investigate the influence of caloric and noncaloric food on plasma ghrelin and obestatin concentrations in healthy women (n = 6; age 23.83 +/- 1.1 years; BMI 20.85 +/- 0.87 kg/m2) and in bulimia nervosa patients (n = 6; age 26.6 +/- 5.2 years; BMI 19.2 +/- 1.44 kg/m2), characterized by abnormal eating behaviour and imbalance in energy homeostasis. METHODS AND RESULTS: After overnight fasting, plasma ghrelin and obestatin were measured by commercial radioimmunoassay kits before and after consumption of soluble fiber alone or with glucose. In both groups plasma ghrelin and obestatin levels did not change after fiber alone, but decreased after fiber with glucose. During 30-90 min after ingestion we observed significant decrease (p < 0.05) of plasma ghrelin and obestatin levels after soluble fiber with glucose in healthy women and also in patients with bulimia nervosa, after then the levels of both hormones started to increase to preprandial levels. CONCLUSIONS: We conclude that postprandial ghrelin and obestatin plasma levels decrease in relation to caloric content of the meal in healthy women and in patients with bulimia nervosa.

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.

Adipose tissue resistin levels in patients with anorexia nervosa.

OBJECTIVE: Resistin is a specific fat-derived hormone that affects fuel homeostasis and insulin action in rodents. However, its role in human physiology and pathophysiologic conditions, such as malnutrition, remains uncertain. METHODS: To enhance understanding of the role of resistin in the pathophysiology of anorexia nervosa (AN), we measured plasma resistin levels in 13 women with a restrictive type of AN and in 16 healthy age-matched women (control). Further, we measured resistin levels in the subcutaneous adipose tissue of eight women from the AN group and eight women from the control group with an in vivo microdialysis technique (CMA/107 pump, CMA/60 catheters, CMA Microdialysis AB, Solna, Sweden). RESULTS: Body mass index, percentage of body fat, fasting plasma leptin and insulin, and homeostasis model assessment index for insulin resistance were severely decreased in patients with AN compared with the control group. Plasma resistin levels were significantly decreased in patients with AN (P < 0.05), whereas subcutaneous adipose tissue resistin levels were significantly increased in patients with AN compared with the control group (P < 0.05). In both groups, plasma resistin levels showed no significant relation to resistin in dialysate, percentage of body fat, body mass index, homeostasis model assessment index for insulin resistance, and fasting plasma leptin levels. CONCLUSION: We demonstrated that AN is associated with decreased plasma resistin levels and increased resistin levels in extracellular space of the abdominal adipose tissue. Plasma resistin levels in patients with AN or in healthy normal-weight women were not directly related to body mass index, percentage of body fat, plasma leptin levels, and insulin sensitivity.

Leptin concentrations in the abdominal subcutaneous adipose tissue of patients with anorexia nervosa assessed by in vivo microdialysis.

OBJECTIVE: The adipocyte-derived hormone leptin is involved in energy metabolism and body weight regulation. Plasma leptin concentrations are significantly reduced in patients with anorexia nervosa (AN) and with severe malnutrition. Whether reduced plasma leptin is reflected by its decreased production by the adipose tissue is unknown. METHODS: In the present study we measured leptin concentrations locally in the abdominal subcutaneous adipose tissue of 9 female AN patients and 11 healthy controls by in vivo microdialysis. RESULTS: Adipose tissue free leptin levels were not different in patients with AN compared to controls (2.59+/-1.99 vs 2.36+/-0.25 ng/ml, P>0.05). Plasma leptin soluble receptor (sOb-R) levels were significantly higher in patients with AN than in healthy subjects (58.05+/-38.69 vs 12.79+/-5.08 U/ml, P<0.01). The area of adipocyte in AN was considerably smaller than in the controls (183+/-104.01 microm2 compared to 2145.8+/-1003.41). CONCLUSIONS: We conclude that decreased plasma leptin levels in patients with AN are not directly related to dialysate leptin levels in the abdominal subcutaneous adipose tissue.

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.