血清瘦素与相关疾病

血清瘦素为脂肪组织分泌的具有内分泌激素特性的脂肪细胞因子,参与人体能量平衡的调节。近年来的研究显示,瘦素与某些疾病的发生、发展密切相关。现就瘦素的生物学特性及其与相关疾病的关系进行综述。     

Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease

AIM： To determine the role of leptin system in non-alcoholic fatty liver disease （NAFLD） development by delineating the changes in serum levels of leptin and soluble leptin receptor （sOB-R）.
METHODS： Blood samples were collected from 30 consecutive patients with liver-biopsy-proven NAFLD and 30 patients with cholecystolithiasis （stationary phase） as controls. Serum leptin levels were determined by radioimmunoassay and concentration of sOB-R was measured by ELISA. Body mass index （BMI） was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected.
RESULTS： Mean serum leptin level and BMI in the NAFLD group were significantly higher than in the controls （both P 〈 0.001）, but mean sOB-R level was lower in the NAFLD group when compared to the controls. Both men and women in the NAFLD group had higher mean serum leptin levels and lower sOB-R levels than did the men and women in the control group （all P 〈 0.001）. There was a significant negative correlation between serum leptin and sOB-R levels （r = -0.725, P 〈 0.001）. Multivariate analysis showed that the percentage of hepatocyte steatosis, sex, BMI, and homeostasis model assessment of insulin resistance （HOMA IR） were independently related to serum leptin levels.
CONCLUSION： Elevated serum leptin seems to be afeature of steatosis, and serum leptin seems to increase as hepatocyte steatosis develops. An enhanced release of leptin is accompanied by an decrease in sOB-R concentration, which suggests higher resistance of peripheral tissues towards the action of leptin.     

Serum leptin concentrations in endometriosis

It has been recently reported that serum concentrations of the adipocyte-derived hormone leptin are increased in patients affected by endometriosis. On the basis of these findings, the present study was undertaken to evaluate whether the protein may be used as a new serum marker of the disease. A consecutive series of 67 reproductive-age women who underwent laparoscopy for benign gynecological pathologies were enrolled prospectively for the study. Serum leptin concentrations, as evaluated by a conventional RIA kit, were related to baseline clinical characteristics and surgical and histologic diagnosis. Endometriosis was documented in 42 women (stage I-II in 19 patients and stage III-IV in 23 patients). Twenty-five women of similar age and body mass index, who had no laparoscopic evidence of the disease, served as control group. Serum levels of leptin resulted similar between women without and with endometriosis at any stage (mean +/- SEM, 12.5 +/- 9.4 ng/ml and 12.1 +/- 8.0 ng/ml, respectively). No significant association with leptin concentrations was observed in regard to stage of the disease, number of endometriotic implants, presence/absence of an endometriotic cyst or peritoneal deep endometriosis, and presence/absence of specific symptoms. Therefore, our results do not support the possibility to employ leptin measurement as a diagnostic tool for endometriosis. Further studies are needed to elucidate the relationship between leptin and endometrial system and determine the potential contribution of the molecule in implantation and early pregnancy development.     

Serum leptin in rheumatoid arthritis

Leptin is a peptide hormone that has an essential role in the regulation of body weight by inhibiting food intake and stimulating energy expenditure. The role of leptin in the modulation of the immune response and inflammation has been regarded as important. In rheumatoid arthritis (RA) patients it was reported that fasting leads to an improvement of clinical and biological measures of disease activity, which was associated with a marked decrease in serum leptin. These features suggest that leptin may also influence the inflammatory mechanisms of arthritis in humans. In this study we assessed serum leptin levels in RA and osteoarthritis (OA) patients and found a correlation between serum leptin level and other markers as well as bone mass density changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA and 30 OA patients who constituted the control group. Serum leptin level was determined using the DRG Leptin ELISA Kit—a solid phase enzyme—linked immunosorbent assay based on the sandwich principle. The serum level of leptin in RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a positive correlation between body mass index (BMI) of RA patients and serum level of leptin (correlation coefficients Spearman’s r = 0.81). According to correlation coefficients, serum leptin level is independent of age of RA patients, stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration as well as value of titre of the Waaler–Rose, disease activity score (DAS 28) value and presence of rheumatoid nodules. There was a negative correlation between serum leptin level and glomerular filtration rate (GFR). No correlation between the serum leptin level and T-score was found. An influence of steroid treatment on the serum leptin level was not shown. The median serum leptin level in OA patients was 9.2 ng/ml. There was a positive correlation between body mass index of OA patients and serum level of leptin (correlation coefficients Spearman’s r = 0.57). No correlation was found between serum leptin level and patient’s age, duration of disease and value of laboratory data. There were no correlations between serum leptin level and visual analogue pain scale (VAS) for the lower-limb afflicted patients as well as stage of disease according to Kellgren and Lawrence’s score in OA patients. There was a negative correlation between serum leptin level and T-score value in OA patients (r = −0.58, P < 0.05). No statistically significant differences were found between serum leptin levels for RA and OA patients.     

Serum leptin and myocardial infarction in hypertension

The adipose tissue-derived hormone leptin is among the physiologic processes involved in cardiovascular regulation. The aim of the present study was to elucidate if serum leptin may predict cardiovascular risk, particularly myocardial infarction (MI), in hypertensive men and women. In a prospective study cohort of hypertensive men and women, serum leptin was compared in 171 patients with MI and in 342 matched controls. The mean serum concentration of leptin was 25.1 ± 20.0 ng/ml in the MI patients and 20.0 ± 16.6 ng/ml in the controls (p = 0.007). The association between serum leptin and MI was independent of traditional risk factors. Leptin concentrations were higher in women than in men. In women, serum leptin was the most important predictor of MI. The present study indicates that serum leptin is associated with MI in a hypertensive population. Leptin concentrations may be of practical importance when estimating the risk of MI, especially in women, where leptin was found to be the most important predictor for MI.     

心钠素基因多态性与2型糖尿病肾病易感性的关联研究

糖尿病肾病是 2型糖尿病的主要晚期并发症之一 ,其确切发病机制及遗传学基础尚未完全阐明。在遗传学水平早期发现糖尿病肾病高危人群 ,并对其进行积极合理的治疗可预防或延缓糖尿病肾病的发生和发展。本研究通过对 2型糖尿病正常白蛋白尿组、临床肾病组 (包括微量白蛋白尿及大量白蛋白尿 )及正常对照组之间心钠素 (ＡＮＦ)基因Ｃ/Ｔ多态性频率差异的研究 ,旨在观察ＡＮＰ基因多态性与 2型糖尿病肾病之间的关联 ,进而评估该基因多态性在 2型糖尿病肾病中的作用。一、对象和方法1.对象 :据 1985年ＷＨＯ诊断标准确诊的 2型糖尿病患者 (ＤＭ组 …     

Serum leptin in systemic lupus erythematosus

Leptin, a peptide hormone, plays an essential role in the regulation of body weight, the endocrine function, reproduction, the immune response and inflammation. The immune system, in turn, modifies leptin’s production. Systemic lupus erythematosus (SLE) is an autoimmunological disease characterized by widespread inflammation with possible involvement of each body organ and system. In this study, we assessed serum leptin levels in SLE patients and the control group in search for correlations between leptin concentrations and other markers’ level, the activity of the disease, its duration, the age of the patients and their bone mineral density. Blood samples were collected from 30 SLE and 30 control group women. Each SLE patient was matched with one from the control for age (±1 year) and the body mass index (BMI; ±1). Serum leptin levels were determined using the DRG Leptin ELISA Kit. Serum leptin levels in SLE patients ranged from 1.8 to 66.3 ng/ml (median value 7.5), and in control group it was 8.8 ng/ml (0.7–39.2) (NS). In SLE, serum leptin levels (after the logarithmic transformation) correlated with BMI (r = 0.89, P < 0.0001), the age (r = 0.34, P < 0.01) and the patients’ disease duration (r = 0.59, P < 0.0005). Serum leptin levels in SLE patients with arthritis (P < 0.05) and central nervous system (CNS) involvement (P = 0.05) were significantly lower in comparison with serum leptin levels in SLE patients without arthritis and CNS involvement. No correlation was found between serum leptin levels and the T-score. In the control group, the logarithmic transformation of serum leptin levels positively correlated with BMI (r = 0.52, P < 0.05). No differences in serum leptin levels were shown between SLE patients and the control group. However, we found correlation between BMI and serum leptin levels in both groups. Furthermore, serum leptin levels in SLE patients with arthritis and CNS involvement were significantly lower in comparison with SLE patients without arthritis and CNS involvement, which suggests that active chronic inflammation may lower plasma leptin concentrations.     

Serum leptin levels in marasmic children and the relationship between leptin and lipid profile

BACKGROUND AND AIMS: Leptin and dyslipidemia are risk factors for cardiovascular disease. We measured leptin and lipid levels, and examined whether there is an effect of leptin on lipid profile in marasmic children. METHODS: Fifty children (25 marasmic, 25 healthy) aged between 0.3 and 2.5 years were evaluated. Leptin levels were compared with lipid profile in marasmic and healthy children. The relationships between leptin and sex, body mass index and lipid profile were investigated in marasmic children. RESULTS: In the marasmic group, body mass index, leptin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p < 0.0001, p < 0.0001, p = 0.01, respectively), and triglyceride levels higher than in the control group. In females, leptin was correlated positively with high-density lipoprotein cholesterol (p = 0.002), and inversely correlated with the triglyceride level (p = 0.003). In males, a positive correlation was found between leptin and low-density lipoprotein cholesterol (p = 0.026). In female patients, body mass index, leptin and high-density lipoprotein cholesterol levels were lower (p < 0.0001, for all) when compared to their female controls. In male patients, body mass index, leptin, high-density lipoprotein and low-density lipoprotein cholesterol levels were lower (p < 0.0001, p = 0.031, p = 0.002, p = 0.017, respectively) than those in their male controls. CONCLUSION: As a result, we found low leptin (an independent cardiovascular risk factor) levels, but dyslipidemia in our marasmic patients. Dyslipidemia may be a risk factor for cardiovascular complications in marasmic children in the future.     

Serum leptin levels in acute myocardial infarction

BACKGROUND: Several studies have shown an association of serum leptin levels with cardiovascular diseases. The present study was undertaken to assess levels of serum leptin in patients presenting with acute ST segment elevation myocardial infarction. METHODS AND RESULTS: Ninety-four consecutive patients presenting with acute ST segment elevation myocardial infarction were studied and 46 controls were taken from patients who presented with chest pain but had no history of myocardial infarction in the past. There were 59 patients with anterior wall infarction and 31 had inferior wall infarction and in 4 it was a combination of anterior and inferior wall infarction. The serum leptin levels in patients with myocardial infarction was 6.51 +/- 6.76 ng/ml versus 2.86 +/- 2.22 ng/ml in controls. In the multivariate analysis the odds ratio for serum leptin with myocardial infarction was 1.45 with a 95% confidence interval of 1.2 to 1.8. CONCLUSIONS: Our results suggest that serum leptin level is elevated in patients with acute ST segment elevation myocardial infarction.     

Serum leptin levels in childhood celiac disease

OBJECTIVE: Leptin has effects on growth and is also involved in immune regulation. We thought that with its intestinal histopathologic alterations due to immune mechanisms, and subsequent malnutrition and/or growth failure, celiac disease (CD) deserves interest regarding leptin status. METHOD: Serum leptin levels of 19 children with CD on admission and 1 year after gluten-free diet (GFD) and of 16 healthy children were determined. RESULTS: Mean age was 9.7+/-3.3 years. Mean serum leptin level of children with CD on admission and of healthy children were 1.60+/-0.63 ng/mL, and 3.98+/-1.49 ng/mL, respectively (P: 0.0001). Mean serum leptin level under GFD was 4.55+/-1.97 ng/mL. There was a statistical significant difference between serum levels determined before and 1 year after GFD (P: 0.001) and between those of under GFD and healthy children (P: 0.001). Of 19 patients with CD, 10 (52.6%) showed Marsh IIIc, other 9 (47.4%) showed Marsh IIIa histologic lesions. Mean serum leptin level of children with Marsh IIIc and Marsh IIIa were not different (1.70+/-0.73 ng/mL vs. 1.45+/-0.59 ng/mL). Leptin was correlated with body mass index in healthy children, and in CD both before and after GFD (P<0.001). Mean lumbar z score of the patients on admission and after GFD were 2.7+/-1.3 and 1.9+/-0.8, respectively (P: 0.048). Serum leptin level was not correlated with lumbar z score either before or after GFD. CONCLUSIONS: Serum leptin level is affected in childhood CD, it is not directly related to histopathologic findings, and is responsive to GFD. Further studies investigating its level in different clinical and histopathologic presentations might give clear clues about the role of leptin in CD.     

Serum adiponectin and leptin levels in patients with lipodystrophies

Lipodystrophies are characterized by selective but variable loss of body fat and metabolic complications of insulin resistance. We hypothesized that reduced synthesis and secretion of adipocyte-specific proteins may be related to the metabolic complications of lipodystrophy. Therefore, we compared fasting serum concentrations of adiponectin and leptin, in 18 patients with congenital generalized lipodystrophy (CGL), 11 with acquired generalized lipodystrophy (AGL), 46 with familial partial lipodystrophy-Dunnigan variety (FPLD) and 18 with acquired partial lipodystrophy (APL) and studied their relationship to metabolic parameters. Patients with CGL and AGL had markedly reduced serum adiponectin levels compared to those with FPLD and APL (median [range]: 1.5 [0.4-7.5], 3.2 [0.6-7.7], 6.9 [1.9-23.2] and 7.9 [3.1-13.3] microg/mL, respectively, p < 0.0001); the same trend was noted for serum leptin levels (0.63 [0.05-3.7], 2.18 [0.05-11.30], 2.86 [0.23-9.00] and 6.24 [1.21-10.4] ng/mL, respectively, p < 0.0001). Serum adiponectin levels correlated negatively with fasting serum triglycerides (r = -0.6, p < 0.001) and insulin levels (r = -0.5, p < 0.0001) and positively with serum high-density lipoprotein cholesterol levels (r = 0.5, p < 0.001). Serum adiponectin levels were lower in patients with diabetes compared to non-diabetic subjects (3.0 vs. 7.1 microg/mL, p < 0.001). Our results indicate that serum adiponectin and leptin levels are extremely low in patients with generalized lipodystrophies and may be related to severe insulin resistance and its metabolic complications in lipodystrophies.     

酒精性肝病患者血清瘦素及其受体基因Gln223Arg多态性变化

目的 观察酒精性肝病患者血清瘦素（Lep）水平及其受体（LEPR）基因Gln223Arg多态性变化,并探讨其意义.方法 选择酒精性肝病患者106例,其中酒精性脂肪性肝炎45例（AH组）,酒精性肝硬化61例（AC组）,同期健康体检者65例作为对照组.采用ELISA法检测血清Lep,葡萄糖氧化酶—过氧化物酶法检测空腹血糖（FPG）,化学发光免疫分析法检测空腹血清胰岛素（FINS）,PCR-RFLP法检测LEPR基因Gln223Arg多态性,并计算HOMA-IR.结果 AH组血清Lep、HOMA-IR分别为（8.95±1.81） ng/mL、2.44±0.25,AC组分别为（10.57±2.00） ng/mL、3.21 ±0.17,对照组分别为（4.44±0.81） ng/mL、1.77 ±0.18;AH组、AC组与对照组比较,P均＜0.05.AH组、AC组血清Lep与HOMA-IR均呈正相关（r=0.45、0.38,P均＜0.01）.AH组AA、A/G、GG的例数分别为3、11、31例,AC组分别为0、25、36例,对照组分别为1、12、52例;AC组与对照组比较,P＜0.05.结论 酒精性肝病患者血清Lep、HOMA-IR水平升高,AC组患者LEPR基因Gln223 Arg杂合基因频率高于健康人群,可能通过胰岛素—瘦素轴促进胰岛素抵抗,影响体内脂肪代谢,参与酒精性肝病的发病机制.     

Serum leptin, soluble leptin receptor, free leptin index and bone mineral density in patients with primary biliary cirrhosis

BACKGROUND/AIM: The pathophysiology of osteoporosis in chronic liver diseases is unknown. Recent data suggest that serum leptin is associated with bone mineral density (BMD). In animal studies leptin was found to be a potent inhibitor of bone formation. We investigated the relationship between serum leptin levels, soluble leptin receptor (sOB-R), free leptin index (FLI) and BMD in patients with primary biliary cirrhosis (PBC). PATIENTS AND METHODS: Ninety-four female patients with PBC were included in this study; 122 healthy women served as controls. Serum leptin levels were measured by radioimmunoassay, sOB-R by enzyme-linked immunosorbent assay. BMD was measured by dual energy X-ray absorptiometry in the lumbar spine and femoral neck. RESULTS: Serum leptin was significantly lower in patients with PBC compared with healthy controls. No difference was found between the body mass index (BMI) of patients and controls. There was a strong positive correlation between leptin and BMI. In PBC no association was found between leptin, sOB-R and liver function tests, histological stages or the presence of osteoporosis. Osteoporosis was present in 38 patients. A positive correlation was found between serum leptin and femoral neck z-score even after adjustment for BMI, whereas serum sOB-R correlated inversely with the serum leptin level. There was no difference in FLI between the subgroups of PBC patients according to the stages of the disease. CONCLUSIONS: We found a lower serum leptin level and a higher sOB-R in patients with PBC, which could not be explained by the difference in BMI. As leptin was associated with BMD, it may be hypothesized that leptin is involved in the complex regulation of bone metabolism in PBC.     

Serum leptin levels in patients with nonalcoholic steatohepatitis

OBJECTIVE: Leptin is a peptide hormone that mainly regulates food intake and energy expenditure of human body. A close correlation between serum leptin levels and the percentage of body fat stores is well known. Nonalcoholic steatohepatitis (NASH) is a common disorder which causes serum liver enzyme elevation. In this study, the serum leptin levels were investigated in patients with NASH to determine a possible role in the pathogenesis and in patients with chronic viral hepatitis to ascertain the effect of hepatic inflammation on serum leptin level. METHODS: Forty-nine patients (38 men, 11 women) with NASH diagnosed by biopsy, 32 patients with biopsy-proven chronic viral hepatitis (21 men and 11 women), and 30 healthy adults (17 men, 13 women) enrolled in the study. Fasting blood samples were obtained, and serum leptin levels were measured by ELISA. Body mass index (BMI) was calculated for all subjects, and serum insulin, C-peptide, and lipoprotein levels were also detected. RESULTS: The mean serum leptin levels (+/-SEM) were 6.62 +/- 0.71, 4.24 +/- 1.0, and 4.02 +/- 0.46 ng/ml in NASH, chronic hepatitis, and the control group, respectively. Mean serum leptin level in the NASH group was significantly higher than those in the other groups tested. BMI was also slightly higher in the NASH group when compared to the other groups (26.7 +/- 0.3, 23.7 +/- 0.6, and 24.6 +/- 0.3, respectively). There was a significant correlation between BMI and serum leptin levels when all the subjects were evaluated together (NASH, hepatitis, and control groups, r = 0.337, p = 0.012) but not in the NASH group when evaluated alone (r = 0.238, p = 0.1). Of the predisposing factors for NASH, obesity was observed in 24% of patients and hyperlipidemia in 67%. Serum cholesterol and triglyceride levels were significantly higher in the NASH group than those in controls (p < 0.05). It has been detected that most of these patients consumed high amounts of fat in their dietary habits. CONCLUSIONS: The serum leptin levels were significantly higher in patients with NASH, while they were not affected by chronic hepatitis. This elevation is out of proportion to BMI of these patients and may be related to hyperlipidemia in most. Elevated serum leptin levels, therefore, may promote hepatic steatosis and steatohepatitis.     

Serum leptin level in patients with functional dyspepsia

BACKGROUND/GOAL: Previous studies have shown that leptin plays a major role in the amount of food consumption. Recently, leptin and its receptors have been found in the human gastric mucosa. The aim of this study was to seek any possible correlation between serum leptin level and subtypes and pathological findings in functional dyspepsia. MATERIALS AND METHODS: In a prospective study, we randomly select 44 patients as dysmotility-like and ulcer-like dyspepsia (according to ROME II criteria) in two equivalent groups and compared them with 22 healthy volunteers control group who matched the patients in relation to age, sex and body mass index. From each patient, a fasting blood sample for leptin level and two antral biopsies for evaluating the intensity of gastritis and Helicobacter pylori infection were provided and compared with the control group. RESULTS: Compared to the control group, serum leptin level was significantly higher in patients with dysmotility-like dyspepsia (P < 0.05). Leptin level were also significantly correlated with the presence of gastritis and H. pylori infection (P < 0.05). CONCLUSION: Leptin may have a role in the pathogenesis of the dysmotility variety of non-ulcer dyspepsia through mechanisms other than H. pylori infection. Further studies based on gastric leptin immunohistochemistry may need correlation between symptoms of functional dyspepsia and gastric leptin expression.