The objective of this work was to test in type II diabetics with hyperlipoproteinaemia the action of a new analogue of nicotinic acid--Acipimox (Olbetam, Farmitalia Carlo Erba). The investigation comprised 24 patients of whom 16 took for three months Olbetam (250 mg 3 x per day by the oral route) and 8 patients were given placebo. The investigated biochemical parameters were examined before administration of the preparation was started and 4 and 12 weeks following its administration. Contrary to the group taking placebo, in the group taking Olbetam a significant decline of the triglyceride serum level occurred and a slight decline of total serum cholesterol levels and increase of HDL-cholesterol and the atherogenic risk indexes were thus more favourable. The results indicate that Olbetam is a satisfactory hypolipidemic agent for the treatment of diabetic hyperlipoproteinaemia.

• MeSH
• diabetes mellitus 2. typu krev   komplikace   MeSH
• dospělí MeSH
• hyperlipoproteinemie krev   komplikace   farmakoterapie   MeSH
• hypolipidemika terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• pyraziny terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH
• klinické zkoušky MeSH
• Názvy látek
• acipimox MeSH Prohlížeč
• hypolipidemika MeSH
• lipidy MeSH
• pyraziny MeSH

BACKGROUND: Hypertriglyceridaemia associated with low HDL-concentrations is considered an independent risk factor of ischaemic heart disease. The drug of choice in this disorder is nicotinic acid. The aim of the presented work was to compare the hypolipidaemic effect of fish oils rich in omega-3 fatty acids (Activepa 30-TGR, Hydromartens, Norway) with a nicotinic acid derivative, acipimox (Olbetam, Farmitalia Carlo Erba, Italy). METHODS AND RESULTS: The preparations were administered for a three-week period to two groups of patients with hypertriglyceridaemia and low HDL cholesterol levels. The groups had comparable body weights and baseline parameters of lipid metabolism. In the group treated with Olbetam (750 mg/day), 17x hyperlipoproteinaemia type IV and 6x IIB) after treatment significant changes of the following parameters were recorded: triglycerides (-18%; P < 0.001), HDL cholesterol (+19%; P < 0.01), HDL2 and HDL3 cholesterol (+33%; +14%; P < 0.001, P < 0.01), apo B (+25%; P < 0.01), apo A-I (+7%; P < 0.01), ratio of apoB/A-I (+17%; P < 0.01). Furthermore, there was s drop of the atherogenic index (total cholesterol/HDL cholesterol) by 22% (P < 0.001). In the group of subjects (17x type IV and 8x type IIB) whose diet was enriched with omega-3 fatty acids (3.5 g/day), the following parameters changed significantly: triglycerides (-44%; P < 0.001), the atherogenic index (-23%; P < 0.001), HDL cholesterol (+11%, P < 0.01), HDL2 and HDL3 cholesterol (+13%, +17%; P < 0.01, P < 0.05). Changes of apo B, apo A-I concentrations and their ratios were not significant. Comparison of the effect of the two preparations on the investigated parameters revealed a more marked rise of the HDL cholesterol (P < 0.05), apo B (P < 0.01) concentrations and the apo B/-A-I ratio (P < 0.05) during Olbetam treatment. As to the action of the two preparations on further investigated parameters (total and LDL-cholesterol), no significant differences found. CONCLUSIONS: The assembled results indicate that enrichment of the diet with fish oil rich in omega-3 fatty acids has a hypolipidaemic effect comparable to acipimox. It is thus feasible to use fish oils as a drug of first choice in the treatment of hypertriglyceridaemia associated with a reduction of HDL cholesterol concentration.

• MeSH
• hypertriglyceridemie farmakoterapie   MeSH
• hypolipidemika terapeutické užití   MeSH
• kyseliny mastné omega-3 terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pyraziny terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• acipimox MeSH Prohlížeč
• hypolipidemika MeSH
• kyseliny mastné omega-3 MeSH
• pyraziny MeSH

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.

• MeSH
• adrenokortikotropní hormon krev   MeSH
• bulimia krev   rehabilitace   MeSH
• cvičení * MeSH
• dospělí MeSH
• jednoduchá slepá metoda MeSH
• lidé MeSH
• pyraziny aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• acipimox MeSH Prohlížeč
• adrenokortikotropní hormon MeSH
• pyraziny MeSH

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.

• MeSH
• bulimia nervosa krev   patofyziologie   MeSH
• cvičení fyziologie   MeSH
• dospělí MeSH
• experimenty na lidech MeSH
• ghrelin * biosyntéza   metabolismus   MeSH
• glycerol krev   MeSH
• hypofýza účinky léků   metabolismus   MeSH
• hypolipidemika aplikace a dávkování   MeSH
• index tělesné hmotnosti MeSH
• kyseliny mastné neesterifikované krev   MeSH
• lidé MeSH
• lidský růstový hormon * biosyntéza   metabolismus   MeSH
• neuropeptid Y krev   MeSH
• pyraziny aplikace a dávkování   MeSH
• studie případů a kontrol MeSH
• žaludeční sliznice metabolismus   MeSH
• žaludek účinky léků   MeSH
• zpětná vazba fyziologická * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acipimox MeSH Prohlížeč
• ghrelin * MeSH
• glycerol MeSH
• hypolipidemika MeSH
• kyseliny mastné neesterifikované MeSH
• lidský růstový hormon * MeSH
• neuropeptid Y MeSH
• pyraziny MeSH

Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results, P less than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.

• Klíčová slova
• diabetes, insulin resistance, intermittent hypoxia, lipolysis, obstructive sleep apnea,
• MeSH
• adipozita účinky léků   MeSH
• experimentální diabetes mellitus krev   komplikace   genetika   patologie   MeSH
• fenotyp MeSH
• glukosa metabolismus   MeSH
• hypoxie komplikace   metabolismus   MeSH
• inzulin metabolismus   MeSH
• lipolýza * účinky léků   MeSH
• mastné kyseliny krev   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• obstrukční spánková apnoe krev   komplikace   genetika   patologie   MeSH
• pyraziny farmakologie   MeSH
• regulace genové exprese účinky léků   MeSH
• signální transdukce účinky léků   MeSH
• tukové buňky účinky léků   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• acipimox MeSH Prohlížeč
• glukosa MeSH
• inzulin MeSH
• mastné kyseliny MeSH
• pyraziny MeSH

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.

• Klíčová slova
• eating disorders, exercise, ghrelin, growth hormone, human adipose tissue, microdialysis, olbetam, pancreatic polypeptide family,
• Publikační typ
• časopisecké články MeSH

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.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: To study the effect of lipid depressing drugs on (18)FDG myocardial concentration. The changes of (18)FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. MATERIAL AND METHODS: 5.55 MBq of (18)FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal (18)FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before (18)FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before (18)FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before (18)FDG). The animals were killed 45 minutes following (18)FDG injection. RESULTS: Tyloxapol and acipimox significantly elevated myocardial (18)FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in (18)FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in (18)FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of (18)FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. CONCLUSION: The highest (18)FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium.

• Publikační typ
• časopisecké články MeSH