Increasing hypothalamic nucleobindin 2 levels and decreasing hypothalamic inflammation in obese male mice via diet and exercise alleviate obesity-associated hypogonadism

To explore the role of nesfatin-1 in regulating male reproductive function during energy balance variation, we employed an obese mouse model which was first induced by a high-fat diet (HFD) and followed by interventions of a normal diet (ND) and/or moderate exercise, and then serum reproductive hormones of male mice, hypothalamic nucleobindin 2 (NUCB2)/nesfatin-1, inflammatory factors, and gonadotropin-releasing hormone (GnRH) levels were tested. Our findings showed that both serum nesfatin-1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels and hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels were reduced, whereas, the mRNA and protein levels of hypothalamic tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, inhibitor kappa B kinase β (IKKβ), and nuclear factor (NF)-κB were increased in obese male mice. Diet, exercise, and diet combined with exercise interventions reversed the decreases in serum nesfatin-1, FSH, LH, and T levels; increased hypothalamic NUCB2/nesfatin-1 and Gnrh mRNA levels; and reduced hypothalamic TNF-α, IL-1β, IKKβ, and NF-κB levels. These changes were accompanied by reduced adiposity, and these effects were more obvious in the diet combined with exercise group. Overall, our findings suggested that the hypogonadotropic hypogonadism associated with obesity may be induced by reduced hypothalamic NUCB2/nesfatin-1 levels, which attenuated the stimulatory effect on GnRH directly or indirectly by suppressing its anti-inflammatory effect in the brain. Diet and/or exercise interventions were able to alleviate the hypogonadotropic hypogonadism associated with obesity, potentially by increasing hypothalamic NUCB2/nesfatin-1 levels.     

Serum ghrelin levels are enhanced in patients with epilepsy.

PURPOSE: In patients with epilepsy, although many changes in the physiology of hormones in the neuroendocrine system can occur (especially in the sex hormones, for example), the causes of these changes have not been fully elucidated. There are also relations between seizure activity and stages of sleep. Ghrelin is the peptide hormone, which has been shown to affect both endocrine function and sleep. The purpose of this study was to evaluate serum levels of ghrelin in epilepsy patients. METHODS: A total of 35 patients currently receiving antiepileptic drug therapy (of these patients, 20 had primary generalized seizure and 15 had partial seizure) were studied. The control group consisted of 30 healthy volunteers matched for age and gender. In all participants, serum levels of ghrelin, cholesterol and triglycerides were measured and body mass index (BMI) was determined. Patients with endocrine, immune or any other chronic diseases were excluded. RESULTS: In the epilepsy patients, the mean serum ghrelin level was 158.81+/-55.97 pg/ml, and this was significantly higher than the control group's level of 93.43+/-21.33 pg/ml (p<0.001). In terms of serum cholesterol, triglycerides and BMI, no significant differences were found between the epilepsy patients and the control group (p>0.05). CONCLUSIONS: The origin of higher serum ghrelin levels in epilepsy and their relation to seizures are not completely known. However, this elevation of serum ghrelin could contribute to the lengthening of NREM sleep in epilepsy patients, thereby playing a role in seizure occurrence. From another direction, high serum ghrelin levels could cause changes and/or dysfunction in hormone secretion and physiology via its effects on growth hormone, and thereby play a facilitating role in seizure occurrence.     

Latent Toxoplasma gondii infection is associated with decreased serum triglyceride to high-density lipoprotein cholesterol ratio in male patients with schizophrenia

BackgroundPrevious studies suggested a complex association between Toxoplasma gondii (TG) infection and host lipid metabolism. Both TG infection and metabolic disturbances are very common in patients with schizophrenia, but this relationship is not clear.MethodsIn this cross-sectional study, we evaluated the association between TG seropositivity, serum lipid levels, body mass index (BMI) and metabolic syndrome (MetS) in 210 male inpatients with schizophrenia.ResultsIn our sample of schizophrenia patients, with the mean age of 43.90 ± 12.70 years, the rate of TG seropositivity was 52.38% and the prevalence of MetS was 17%. Patients with the TG antibodies had lower serum triglyceride levels and body weight compared to TG seronegative patients, despite having more frequently received antipsychotics (clozapine, olanzapine risperidone and quetiapine), which are well known to induce weight gain and metabolic abnormalities. However, the only significant change in metabolic parameters, observed in TG seropositive patients with schizophrenia, was decreased serum triglyceride to high-density lipoprotein cholesterol (HDL-C) ratio. No associations were observed between TG seropositivity and serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and glucose levels, waist circumference, BMI and the rate of MetS.ConclusionThis is the first report of the association between TG infection and decreased serum triglyceride to HDL-C ratio in a sample of carefully selected men with chronic schizophrenia.     

Adipocytokines and ghrelin level of bipolar patients from manic episode to euthymic episode

Purpose: Obesity and metabolic syndrome (MeS) are more frequently observed in bipolar patients than the general population. This may result from the differences of adipocytokines and ghrelin levels in bipolar disorder.

Material and methods: We evaluated the leptin, adiponectin, resistin and ghrelin levels in bipolar patients (n?=?30) in manic episode and in a control group (n?=?30). After treatment, the same patients were evaluated again during the euthymic episode. We also measured the insulin, glucose, insulin resistance (HOMA), trygliceride (TG), total cholesterol (TCHOL), high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL) in relation to the (MeS).

Results: When controlling for age, BMI and glucose, leptin levels were higher in the bipolar disorder manic episode group (BD-ME) and bipolar euthymic episode group (BD-EE) than the control group; resistin levels were higher in the BD-ME compared to the control group and it had a positive correlation with Young Mania Rating Scale (YMRS). After treatment, ghrelin levels were higher in the BD-EE compared to the BD-ME group. There was no difference among the groups with respect to adiponectin.

Conclusions: The present results point that high leptin, resistin and ghrelin levels may be involved in the early pathophysiological process which can lead to later obesity and MeS in patients with bipolar disorder.     

Nesfatin-1 suppresses energy intake, co-localises ghrelin in the brain and gut, and alters ghrelin, cholecystokinin and orexin mRNA expression in goldfish

Nesfatin‐1 is a novel anorectic peptide encoded in the precursor protein nucleobindin‐2 (NUCB2). We recently reported the presence and appetite suppressing effects of nesfatin‐1 in goldfish. Nesfatin‐1 has been co‐localised with ghrelin in the stomach of rats. Whether nesfatin‐1 influences other appetite regulatory peptides in goldfish remains unclear. The main objectives of the present study were to investigate whether nesfatin‐1 co‐localises ghrelin in goldfish, and to test whether exogenous nesfatin‐1 influences endogenous ghrelin, cholecystokinin (CCK) and orexin A (OXA). We found co‐localisation of nesfatin‐1‐like and ghrelin‐like immunoreactivity in the enteroendocrine cells of the goldfish anterior intestine (J‐loop). Furthermore, co‐localisation of ghrelin and nesfatin‐1 was also observed in the posterior nucleus lateralis tuberis of the goldfish hypothalamus, a brain region implicated in the regulation of food intake. These findings suggest a functional relationship between ghrelin and nesfatin‐1 in goldfish. In support of this, i.c.v. administration of goldfish (gf) nesfatin‐1 [25 ng/g body weight (BW)], suppressed food intake and the expression of mRNAs encoding preproghrelin, ghrelin receptor (GHS‐R 1a‐1), CCK and NUCB2 in the forebrain of fed fish, as well as ghrelin and NUCB2 mRNA in the hypothalamus of unfed fish, both at 1 h post‐injection. Nesfatin‐1 stimulated hypothalamic CCK mRNA expression at 30 min post‐injection in fed fish, and inhibited OXA mRNA in the unfed fish hypothalamus 1 h post‐injection. Similarly, i.c.v. injections of gfghrelin (1 ng/g BW), although stimulating food intake, suppressed NUCB2 and preproghrelin mRNAs, but not ghrelin receptor mRNA expression in the forebrain. It is also evident that exogenous ghrelin and nesfatin‐1 mRNAs encoding these peptides. Our novel results indicate interactions between nesfatin‐1 and ghrelin, CCK and orexin, and show that nesfatin‐1 acts on other appetite regulatory peptides in a time‐ and feeding status‐dependent, as well as tissue‐specific, manner in goldfish.     

Serum ghrelin and cholesterol values in suicide attempters

In our previous study, we demonstrated that suicide attempters had statistically significant lower leptin and cholesterol levels compared with healthy controls. In keeping with our previous report regarding lower serum cholesterol and leptin levels in suicide attempters compared with healthy controls, the relationship between cholesterol and leptin, and ghrelin, we aimed to evaluate serum total cholesterol and ghrelin levels in suicide attempters. In the present study, 30 patients with suicide attempts (aged 18-47 years) and the same number of healthy controls were compared with regard to serum total cholesterol and ghrelin levels. The mean cholesterol level of the patients was significantly lower than that of the controls. On the other hand, the suicide attempters had significantly higher ghrelin levels compared with the controls. The results suggest that suicide attempts seem to be associated with decreased serum cholesterol and higher ghrelin values.     

自制α-硫辛酸缓释片对氧化低密度脂蛋白致兔实验性动脉粥样硬化的影响

背景：由于硫酸锌半衰期短,必须多次给药,所以临床常用针剂剂型患者依从性差。 目的：利用食饵性兔动脉粥样硬化模型观察自制α-硫辛酸口服缓释片对动脉粥样硬化的预防作用及其可能途径。 设计、时间及地点：随机对照动物实验,于2008-05/09在南方医科大学珠江医院中心实验室完成。 材料：24只新西兰大白兔喂养1周后随机分成3组,分别为正常组、模型组、硫辛酸组,每组8只。 方法：正常组喂饲普通颗粒饲料。模型组用高脂饲料喂养,即在普通饲料中加入1 g胆固醇和8 g猪油。硫辛酸组用高脂饲料喂养,另外每只兔通过胃管给予自制硫辛酸缓释片300 mg/d。喂饲高脂饲料及预防性用药12周。 主要观察指标：实验结束后分别检测各组血清三酰甘油、总胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、丙二醛、超氧化物歧化酶、氧化低密度脂蛋白、一氧化氮及内皮素1水平。 结果：①纳入24只兔全部进入结果分析,无脱失。②喂饲高脂饲料后,模型组血清中总胆固醇、三酰甘油、低密度脂蛋白胆固醇、丙二醛、氧化低密度脂蛋白及内皮素1水平均显著高于正常对照组(P < 0.05), 高密度脂蛋白胆固醇、超氧化物歧化酶及一氧化氮水平显著低于正常对照组(P < 0.05)。③硫辛酸组血清中总胆固醇、三酰甘油、低密度脂蛋白胆固醇、丙二醛、氧化低密度脂蛋白及内皮素1水平均显著低于模型组(P < 0.05)。硫辛酸组超氧化物歧化酶及一氧化氮水平高于模型组(P < 0.01)。 结论：自制α-硫辛酸缓释片具有预防动脉粥样硬化的作用,其机制可能与其清除超氧阴离子等自由基,减轻氧化低密度脂蛋白对血管内皮细胞的氧化损伤有关。     

Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P <.05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P <.05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P <.05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).     

长期应用托吡酯、丙戊酸钠对于血脂水平的影响

目的 观察长期应用托吡酯、丙戊酸钠单药治疗对癫痫患者血脂水平的影响。 方法 连续入组长期单药应用丙戊酸钠控制良好的癫痫患者28例、单药应用托吡酯控制良好的癫痫患者30例,并选取健康对照60例,观察各组间血脂代谢指标的差异。 结果 丙戊酸钠组血清脂蛋白（a）水平显著高于托吡酯组（P<0.001）及健康对照组（P=0.003）,而总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯水平较其他两组无明显差异。托吡酯组的总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、脂蛋白（a）、甘油三酯水平较对照组均未有显著差异。 结论 长期单药应用丙戊酸钠有可能增加癫痫患者脂蛋白（a）的水平,而长期单药应用托吡酯对于血脂水平影响并不明显。     

Central nesfatin‐1 influences the excitability of ghrelin‐responsive gastric distension neurons in the arcuate nucleus and reduces gastric motility in rats

Although the novel satiety peptide nesfatin‐1 has been shown to regulate gastric motility, the underlying mechanisms have yet to be elucidated. The study aimed to explore the effects of nesfatin‐1 on ghrelin‐responsive gastric distension (GD) neurons in the arcuate nucleus (Arc), and potential regulation mechanisms of gastric motility by the paraventricular nucleus (PVN). Single‐unit discharges in the Arc were recorded extracellularly, and gastric motility in conscious rats was monitored during the administration of nesfatin‐1 to the Arc or electrical stimulation of the PVN. Retrograde tracing and fluo‐immunohistochemistry staining were used to determine NUCB2/nesfatin‐1 neuronal projections. Nesfatin‐1 inhibited most of the ghrelin‐responsive GD‐excitatory neurons, but excited ghrelin‐responsive GD‐inhibitory neurons in the Arc. Gastric motility was significantly reduced by nesfatin‐1 administration to the Arc in a dose‐dependent manner. The firing activity in the Arc and changes to gastric motility were partly reduced by SHU9119, an antagonist of melanocortin 3/4 receptors. Electrical stimulation of PVN excited most of the ghrelin‐responsive GD neurons in the Arc and promoted gastric motility. Nonetheless, pretreatment with an anti‐NUCB2/nesfatin‐1 antibody in the Arc further increased the firing rate of most of the ghrelin‐responsive GD‐excitatory neurons and decreased the ghrelin‐responsive GD‐inhibitory neurons following electrical stimulation of the PVN. Gastric motility was enhanced by pretreatment with an anti‐NUCB2/nesfatin‐1 antibody in the Arc following PVN stimulation. Furthermore, NUCB2/nesfatin‐1/fluorogold double‐labeled neurons were detected in the PVN. These results suggest that nesfatin‐1 could serve as an inhibitory factor in the Arc to regulate gastric motility via the melanocortin pathway. The PVN could be involved in the regulation of the Arc in gastric activity.     

Low and high density lipoprotein metabolism in atherothrombotic brain infarction.

BACKGROUND AND PURPOSE: Elevated low density lipoprotein and reduced high density lipoprotein cholesterol may increase the risk of atherothrombotic brain infarction, but the metabolic mechanisms accounting for this relation are poorly understood. METHODS: The kinetic parameters of low density and high density lipoprotein were studied in nine subjects with atherothrombotic brain infarction or identifiable (by noninvasive testing) extracranial occlusive disease and in 12 control subjects. Autologous iodine-125-labeled lipoproteins were injected intravenously. Blood samples were drawn 10 minutes after injection and periodically thereafter for 10 days. Kinetic parameters were calculated from the decay curves. RESULTS: The stroke-risk group showed significantly higher triglyceride (p less than 0.05), total cholesterol (p less than 0.02), and low density lipoprotein cholesterol (p less than 0.01). The fractional catabolic rate of low density lipoprotein was significantly lower (p less than 0.001) and the high density lipoprotein rate higher (p less than 0.02) in the stroke-risk group than in the control group. Regression analysis (using all subjects) of serum lipoproteins and their respective fractional catabolic rates correlated significantly (for low density lipoprotein, r = 0.684, p less than 0.001; for high density lipoprotein, r = 0.595, p less than 0.002). Mean percent stenosis showed a significant relation with triglyceride level (r = 0.678, p less than 0.01) and low density lipoprotein cholesterol (r = 0.535, p less than 0.02) but not with high density lipoprotein cholesterol. Mean percent stenosis also showed correlation with both fractional catabolic rate of low density lipoprotein (r = 0.667, p less than 0.002) and with serum high density lipoprotein levels (r = 0.504, p less than 0.02). CONCLUSIONS: Our study provides insights into the role of altered low and high density lipoprotein metabolism in the pathogenesis of carotid stenosis. The statistically significant association of serum lipoprotein metabolic rates with carotid stenosis, rather than their respective serum concentrations, implies that metabolic parameters may be more important in predicting stroke risk.     

Serum Ghrelin and Leptin Levels in Patients with Depression and the Effects of Treatment

Objective

Ghrelin and leptin, appetite-regulating hormones, play a role in mood regulation. Current data about the relation between leptin/ghrelin and depression are still controversial. This study aimed to investigate serum leptin and ghrelin levels in patients with depression and the effects of treatment on these levels.

Methods

Serum ghrelin and leptin levels were measured before and after treatment with antidepressant drugs and/or electroconvulsive therapy in 28 patients with depression and once in 21 healthy controls.

Results

Serum ghrelin levels of the patients were high in the pre-treatment. After the treatment, ghrelin levels were not different from those of the controls. We found no difference in serum levels of leptin between the patients and controls and no change with treatment. body mass index of the patients increased after the treatment especially in the drug-treated group.

Conclusion

The present study found increased serum ghrelin levels in depressive patients and normalization with improving of depression but no alteration in leptin levels.     

肉毒碱复合高脂饲料喂养兔血脂水平的变化

背景：肉毒碱是脂肪酸进入线粒体内进行氧化代谢的惟一转运载体，其在机体内水平对血脂代谢具有重要的影响作用。 目的：观察肉毒碱对高脂饲料喂养兔血脂水平变化的影响。 设计、时间及地点：随机对照动物实验，于2006-10/2007-05在解放军南京军区南京总医院检验科及比较医学科完成。 材料：普通级健康纯系雄性新西兰兔14只，体质量(1.98±0.22) kg，用于建立兔高脂血症模型。 方法：14只雄性新西兰兔随机抽签法分为对照组及实验组，每组7只。对照组仅用高脂饲料喂养，实验组用高脂饲料喂养的同时每天补充肉毒碱200 mg/kg 体质量。分别于实验开始后第0，2，3，4周称体质量并抽取耳动脉血，分离血清后测定血中总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇以及载脂蛋白B和血清游离肉毒碱水平。 主要观察指标：不同时间点各组动物体质量的变化以及血中总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇以及载脂蛋白B和血清游离肉毒碱水平。 结果：14只新西兰兔全部进入结果分析。4周内，实验组和对照组体质量差异无显著性意义(P > 0.05)。自第2周开始，实验组兔血清游离肉毒碱水平高于对照组(P < 0.01)；总胆固醇、载脂蛋白B水平明显低于对照组(P < 0.05或P < 0.01)；3周后，实验组血清三酰甘油、低密度脂蛋白胆固醇水平也低于对照组(P < 0.01)；两组高密度脂蛋白胆固醇水平差异无显著性意义(P > 0.05)。 结论：补充服用肉毒碱能够抑制高脂饮食导致的血中总胆固醇、三酰甘油、低密度脂蛋白胆固醇以及载脂蛋白B水平升高。     

普伐他汀对慢性脑缺血大鼠脑海马区早老素-1表达的影响

目的 观察降血脂药普伐他汀对慢性脑缺血(CVI)大鼠脑海马区早老素-1（PS-1）蛋白水平的影响。方法 36只雄性Wistar大鼠随机分为正常对照组(7只),高脂饮食组随机分为空白对照组(6只)、普伐他汀组(7只)、单纯脑缺血组(7只)及脑缺血+普伐他汀组 (9只)。采用永久性结扎双侧颈总动脉建立CVI模型。于术后2个月测血脂,行酶联免疫吸附试验(ELISA)检测血浆及脑左侧海马区匀浆中β淀粉样蛋白(Aβ)水平,蛋白免疫印迹检测海马区PS-1改变。结果 ⑴高脂饮食导致大鼠血浆胆固醇（TC）、三酰甘油(TG)、低密度脂蛋白(LDL-C)显著升高。普伐他汀可使TC降至接近正常水平,LDL-C有不同程度下降,TG无明显改善。⑵各实验组血浆Aβ水平无统计学差异。脑海马区匀浆中,空白对照组、普伐他汀组Aβ轻度升高,而脑缺血组显著升高(P <0.01),普伐他汀可以有效降低脑缺血组Aβ水平(P <0.01)。蛋白免疫印迹结果显示高脂饮食组、空白对照组及脑缺血组PS-1全长蛋白明显上调(P <0.05),而普伐他汀组、脑缺血+普伐他汀组PS-1蛋白可降至接近正常水平。结论 降血脂药物普伐他汀在降低脑缺血后Aβ产生的同时抑制了PS-1的表达上调,可能对阿尔茨海默病有一定的防治作用     

Serum lipids,vitamin B12 and folic acid levels in children receiving long-term valproate therapy

In this study, serum triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), vitamin B12 and folic acid levels were studied in children with epilepsy who had been receiving long-term valproate (VPA) therapy. Our purpose was to determine that whether or not there was any affect of VPA therapy on serum lipids, vitamin B12 and folic acid levels. The study includes 26 patients (13 males, 13 females) with epilepsy who had been receiving long-term VPA therapy and in 28 healthy children (14 males, 14 females). The age ranged from 14 months-12 years (8.22 +/- 3.64 years) and 9 months-18 years (8.97 +/- 4.85 years) in the study and control group, respectively. Because serum lipid ranges may be changed according to the age groups in childhood, the children were divided into three groups as follows; younger than < 5 years, between 5-10 years, and older than > 10 years. The duration of VPA use was between 10 months and 7 years (1.83 +/- 1.80 years). Serum VPA level changed between 42-108 micrograms/ml (75.09 +/- 21.42 micrograms/ml). When comparing the results we did not find any significant difference in all parameters including lipid profiles, vitamin B12 and folic acid levels between the groups (P > 0.05). Additionally, we did not find any correlation between lipid profile and age at start of therapy, duration of therapy, serum VPA level (P > 0.05). In conclusion, our findings showed that VPA therapy did not change serum lipids, vitamin B12 and folic acid concentrations; therefore, we suggest that VPA may be safely used with regard to lipid composition, vitamin B12 and folic acid levels in childhood epilepsy.     

Regulatory effects of paraventricular nucleus injections of ghrelin on the hypothalamus-pituitary-thyroid axis via CB<Subscript>1</Subscript> receptors in male rats

Paraventricular nucleus (PVN) neurons play critical roles in thyrotropin-releasing hormone (TRH) synthesis and the regulation of energetic homeostasis through the hypothalamus-pituitary-thyroid (HPT) axis. Endocannabinoids induce inhibitory effects on TRH-producing neurons via the type 1 cannabinoid receptor [CB₁]. The administration of ghrelin modulates thyrotropes and decreases TSH and T4. The aim of present study was to evaluate the interactions of ghrelin on the HPT axis and CB₁ receptors in the PVN. In this experimental study, 54 male Wistar rats weighing 320–370 g were divided into 10 groups and stereotaxic surgery was performed on all animals. control group received a saline injection, while the experimental groups received one of the following injections: ghrelin (5 nm/μL), ACPA (CB₁ receptor agonist; 1.25, 2.5, or 5 ng/μL), AM251 (CB₁ receptor antagonist; 50, 100, or 200 ng/μL), ACPA + ghrelin (5 ng/μL + 5 ng/μL) and AM251 + ghrelin (200 ng/μL + 5 nm/μL) into the PVN once a day for 3 days. Serum TSH, T₃, T₄, and T₃ uptake levels were evaluated by radioimmunoassay, and FT₄I and FT₃I were calculated. The present study showed that PVN injections of ACPA and ghrelin alone inhibited thyroid gland secretion, and AM251 stimulated this secretion. ACPA and AM251 increased TSH levels, while ghrelin decreased these levels. The coadministration of ACPA with ghrelin increased TSH levels, but AM251 with ghrelin enhanced serum FT₄I. Lastly, injections of ACPA and ACPA with ghrelin decreased thyroid hormones and increased TSH levels. Central injections of ghrelin modulate the HPT axis via the CB₁ receptor. ACPA, ghrelin, and ACPA with ghrelin play inhibitory roles in the regulation of thyroid hormones in the PVN, while AM251 was able to stimulate thyroid hormone secretion.     

Effects of second generation antipsychotics on leptin and ghrelin

BACKGROUND: Weight gain is a major side effect of antipsychotic treatment. Some atypical antipsychotic agents have profound effects on weight. Body weight is regulated by a complex system, including both peripheral and central factors. Two of the hormones that seem to play an important role in the regulation of food intake, energy metabolism, and body weight are leptin and ghrelin. Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. In this present study it is aimed to compare the effects of five different atypical antipsychotic medications on leptin and ghrelin. METHOD: 112 patients who were treated either with clozapine (n=20), olanzapine (n=28), risperidone (n=22), quetiapine (n=20) or amisulpride (n=22) as monotherapy for at least one year and age, gender, and body mass index (BMI) matched control group (n=23) were assessed cross-sectionally. Ghrelin and leptin levels were measured with enzyme-immunoassay. RESULTS: When fasting serum leptin levels were compared between groups, control group had the highest mean value (9.2+/-6.7) and amisulpride group had the lowest mean value (3.7+/-2.1) but still there was no statistically significant difference between six groups (F=1993, p=0.084). In the comparison of the mean values of fasting serum ghrelin levels there was a statistically significant difference between groups (F=11,473, p=0.00). In post-hoc analysis it was seen that the control group had the lowest ghrelin level (194.5+/-86.8). Quetiapine treated group (378.1+/-260.4) had similar fasting serum ghrelin levels to control group. All the other antipsychotic treatment groups had significantly higher levels of fasting serum ghrelin compared to control group, highest in amisulpride treated group (597.0+/-150.0). CONCLUSION: The weight-gain side effect of atypical antipsychotics can be related with the orexigenic effect of elevated serum ghrelin rather than leptin deficit. Among the five widely used atypical antipsychotics quetiapine is the only one which does not elevate the ghrelin level.     

Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism.

BACKGROUND AND PURPOSE: The role of lipoprotein abnormalities in the development of ischemic cerebrovascular disease has not been sufficiently clarified. The aim of this study was to identify the lipoprotein profile in ischemic cerebrovascular disease and the possible role of apolipoprotein E polymorphism. METHODS: The relation between the concentrations of lipoprotein(a), intermediate density lipoproteins, apolipoprotein A-I, apolipoprotein B, apolipoprotein E, and other lipoproteins was studied in 100 men with ischemic cerebrovascular disease (48 atherothrombotic, 28 lacunar, and 24 of unknown type) and in 100 healthy age-matched men as a control group. RESULTS: Patients with ischemic cerebrovascular disease had significantly higher levels of lipoprotein(a), lipids carried by intermediate density lipoproteins, and low density lipoprotein cholesterol and lower levels of high density lipoproteins than control subjects. Patients with atherothrombotic infarction had higher total serum cholesterol and low density lipoprotein cholesterol concentrations than patients with lacunar infarction. To assess lipoprotein abnormalities in normolipidemic subjects, a subgroup of 38 patients with ischemic cerebrovascular disease and 53 control subjects, both with serum cholesterol levels < 5.2 mmol/l (200 mg/dl) and triglycerides < 2.3 mmol/l (200 mg/dl), was analyzed. Serum lipoprotein(a), lipids carried by very low density lipoproteins and intermediate density lipoproteins, and low density lipoprotein triglycerides were significantly higher in normolipidemic patients compared with normolipidemic control subjects, whereas high density lipoprotein cholesterol levels were lower. Apolipoprotein E polymorphism in our ischemic cerebrovascular patients differed from that of the control group, with the epsilon 4 allele being more prevalent. CONCLUSIONS: Increased serum lipoprotein(a) levels and intermediate density lipoprotein abnormalities together with decreased high density lipoprotein levels are major risk factors for ischemic cerebrovascular disease, even in normocholesterolemic and normotriglyceridemic subjects. Finally, the epsilon 4 allele could probably be a predisposing genetic marker for ischemic cerebrovascular disease.     

Differences in cholesterol and metabolic syndrome between bipolar disorder men with and without suicide attempts

Patient with mental illnesses such as schizophrenia and bipolar disorder have an increased prevalence of metabolic syndrome (MetS) and its components compared to general population. Among psychiatric disorders, bipolar disorder ranks highest in suicidality with a relative risk ratio of completed suicide of about 25 compared to the general population. Regarding the biological hypotheses of suicidality, low blood cholesterol level has been extensively explored, although results are still conflicting. The aim of this study was to investigate whether there were differences in the serum cholesterol levels in hospitalized bipolar disorder men patients with history of suicide attempts (N = 20) and without suicide attempts (N = 20). Additionally, we investigated if there were differences in the prevalence of MetS according to NCEP ATP-III criteria in these two groups of patients. Results of the study indicated significantly lower serum cholesterol levels (p = 0.013) and triglyceride levels (p = 0.047), in the bipolar disorder men with suicide attempts in comparison to bipolar disorder men without suicide attempts. The overall prevalence of MetS was 11/40 (27.5%). On this particular sample it was higher in the non-attempters 8/20 (40.0%) than in attempters 3/20 (15.0%) bipolar men group, but without statistical significance. Lower concentrations of serum cholesterol might be useful biological markers of suicidality in men with bipolar disorder.     

Serum lipid levels in patients with dissociative disorder

OBJECTIVE: There may be an association between a low serum cholesterol level and dissociative disorders. METHOD: The subjects of the study were 16 patients with dissociative disorder and 16 normal comparison subjects (two men and 14 women in each group). Total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, and very low density lipoprotein levels were compared. RESULTS: Patients with dissociative disorders had lower serum triglyceride, total cholesterol, low-density lipoprotein, and very low density lipoprotein levels than normal comparison subjects. CONCLUSIONS: Low serum lipid concentrations may be related to a high incidence of self-injurious behaviors and borderline features in patients with dissociative disorders.