Mutations in the human leptin and leptin receptor genes as models of serum leptin receptor regulation

A part of serum Ob leptin, an adipocyte-secreted peptide, is bound to a soluble Ob receptor (sObR). Immunoreactive sObR was measured in 125 lean or obese control subjects (group 1), 18 individuals with a mutation in the leptin gene impairing leptin secretion (group 2), and 10 individuals with a mutation in the ObR gene, leading to production of a truncated ObR not anchored to cell membranes (group 3). In group 1, sObR levels were negatively correlated with age and BMI in children and with BMI in adults. sObR levels were also negatively correlated with leptin levels. Leptin binding activity and sObR levels coeluted in gel-filtration chromatography. In group 2, sObR levels did not differ from those in lean control subjects and were not correlated with BMI. A single peak was detected in chromatographic fractions. In group 3, sObR levels were high and positively correlated with BMI. Immunoreactive sObR coeluted with leptin binding activity. These data demonstrate that leptin is not needed for ObR gene expression, and they suggest that leptin plays a role in receptor downregulation because sObR levels are negatively correlated with leptin levels and BMI in control subjects, whereas sObR levels are not depressed in obese leptin-deficient or leptin receptor-deficient individuals.     

Association of serum leptin with hypoventilation in human obesity

BACKGROUND: Leptin is a protein hormone produced by fat cells of mammals. It acts within the hypothalamus via a specific receptor to reduce appetite and increase energy expenditure. Plasma leptin levels correlate closely with total body fat mass operating via a central feedback mechanism. In human obesity serum leptin levels are up to four times higher than in lean subjects, indicating a failure of the feedback loop and central leptin resistance. In leptin deficient obese mice (ob/ob mice) leptin infusion reverses hypoventilation. It was hypothesised that a relative deficiency in CNS leptin, indicated by high circulating leptin levels, may be implicated in the pathogenesis of obesity hypoventilation syndrome (OHS). METHODS: Fasting morning leptin levels were measured in obese and non-obese patients with and without daytime hypercapnia (n=56). Sleep studies, anthropometric data, spirometric parameters, and awake arterial blood gas tensions were measured in each patient. RESULTS: In the whole group serum leptin levels correlated closely with % body fat (r=0.77). Obese hypercapnic patients (mean (SD) % body fat 43.8 (6.0)%) had higher fasting serum leptin levels than eucapnic patients (mean % body fat 40.8 (6.2)%), with mean (SD) leptin levels of 39.1 (17.9) and 21.4 (11.4) ng/ml, respectively (p<0.005). Serum leptin (odds ratio (OR) 1.12, 95% CI 1.03 to 1.22) was a better predictor than % body fat (OR 0.92, 95% CI 0.76 to 1.1) for the presence of hypercapnia. CONCLUSIONS: Hyperleptinaemia is associated with hypercapnic respiratory failure in obesity. Treatment with leptin or its analogues may have a role in OHS provided central leptin resistance can be overcome.     

Relationships of serum leptin to clinical and anthropometric findings in obese patients

Background: The authors evaluated the relationship between leptin and the clinical, anthropometric and metabolic variables connected to the metabolic syndrome in obese individuals. Methods: A large group of patients with different degrees of obesity was investigated: body mass index (BMI) values, serum leptin, fasting glucose and insulin, triglycerides and HDL-cholesterol concentrations, insulin resistance index and blood pressure were measured. Results: On multiple regression analysis, serum leptin levels appeared to be positively correlated to the BMI and to the serum HDL-cholesterol concentration. Principal component factor analysis revealed three factors, explaining 61.3% of the total variance of the sample. General features of these factors were: factor 1 - BMI values and serum leptin and fasting glucose concentration; factor 2 - systolic and diastolic blood pressure and serum triglycerides and HDL-cholesterol concentration; factor 3 - fasting serum insulin concentration and insulin resistance index. Conclusions: In obese subjects multiple factors underlie the metabolic syndrome and therefore more than one mechanism may account for the clustering characteristics. In obese patients leptin loads only one factor, and therefore leptin does not appear to be a key feature in the metabolic syndrome. On the contrary, multiple correlation and factor analysis data give rise to the hypothesis that in obese patients, leptin may play a protective role against cardiovascular risk.     

Leptin promotes aggregation of human platelets via the long form of its receptor.

Plasma leptin levels are elevated in most obese individuals, and obesity is accompanied by a high incidence of cardiovascular disease. Therefore, leptin could be involved in the pathogenesis of cardiovascular disease. In the present study, the role of leptin was explored in the regulation of platelet function. The expression of the long form of the leptin receptor was detected in human platelets. At 50 ng/ml, human leptin induced phosphorylation of several proteins of platelets at the tyrosine residue. Neither leptin at concentrations < or = 100 ng/ml nor ADP at concentrations > or = 1 micromol/l affected platelet aggregation. However, after pretreatment with 100 ng/ml leptin for 5 min, 1 micromol/l ADP caused aggregation. Thus, leptin and ADP acted synergistically. At a concentration of 2 micromol/l, ADP induced platelet aggregation, which was markedly enhanced by 30-100 ng/ml leptin in a concentration-dependent manner. This concentration range corresponds to that of plasma leptin levels in obese individuals. At the lower concentrations (< 10 ng/ml) that are observed in normal individuals, leptin had no effect on platelet aggregation. In conclusion, leptin at high concentrations has the novel function of promoting platelet aggregation, which may be a key coupling factor between obesity and the cardiovascular disease associated with syndrome X and diabetes.     

血液透析患者血清脂肪因子水平及相关因素初步观察

目的 探讨维持性血液透析患者血清脂肪细胞因子脂联素、瘦素、抵抗素的水平、相关影响因素及相互关系.方法 维持性血液透析患者79例,正常对照组16名.测定2组患者血清脂联素、瘦素、抵抗素、白蛋白、血脂等.分析脂联素、瘦素、抵抗素与这些参数的相关性.结果 维持性血液透析患者甘油三酯、脂联素、瘦素、抵抗素分别为(1.9±0.9)mmol/L、(14±9)mg/L、(105±109)g/L、(0.89±0.33)ng/ml,对照组分别为(1.4±0.5)mnloL/L、(6±4)mg/L、(52±19)异/L、(0.44±0.20)ng//ml,两组比较差异有统计学意义(P<0.05、0.01),而白蛋白(38±4)g/L、高密度脂蛋白(1.3±0.3)mmol/L与对照组[(43±6)g/L、(1.5±0.3)mmol/L]比较差异有统计学意义(P<0.05),维持性血液透析患者胆同醇(4.1±0.9)mmol/L、低密度脂蛋白(2.3±0.7)mmol/L与对照组((4.2±0.9)mmoL/L、(2.1±1.0)mmol/L]比较差异无统计学意义(P>0.05).多元逐步回归分析结果显示,体重指数、高密度脂蛋白、腰臀围比是血清脂联素的独立影响因素.性别和体重指数是血清瘦素的独立影响因素.血清抵抗素与各项临床资料、生化指标的相关性均无显著性.血清脂联素与瘦素呈显著负相关(r:0.232,P<0.01).结论 维持性血液透析患者脂联素、瘦素和抵抗素的水平可能是营养、脂代谢及心血管疾病之间的联系因子.     

Free serum leptin but not bound leptin concentrations are elevated in patients with end-stage renal disease.

BACKGROUND: Leptin is a 16-kDa protein that is thought to be a regulator of food intake and body weight. Although total serum leptin levels have been reported to be elevated in obese and normal weight patients with end-stage renal disease (ESRD), it is not known whether serum-free leptin concentrations are also increased in patients with ESRD with no apparent nutritional problems. Furthermore, there are no data on how different dialysis modes (high-flux haemodiafiltration and low-flux dialysis) influence serum leptin subfractions. METHODS: We measured fasting serum free and bound leptin levels in three groups of male subjects: patients on haemodiafiltration with high flux dialysers (n=11), patients on haemodialysis with low-flux dialysers (n=17) and healthy age (61+/-8 years) and BMI (23.8+/-3.1 kg/m(2)) matched control subjects (n=28). Both leptin components were determined before and after a single dialysis session. RESULTS: Body mass indices were correlated with serum free leptin levels in both patients (r=0.69, P<0.001) and controls (r=0.77, P<0.001). Mean (SD) serum free leptin levels were significantly higher in ESRD patients than in control subjects (91+/-33 vs 41+/- 21 pmol/l; P<0.01). Bound leptin levels did not differ in both groups (0.67+/-0.12 vs 0.56+/-0.11 nmol/l, NS). Elevated serum-free leptin levels in ESRD patients could be reduced by haemodiafiltration with high-flux membranes, but not with low-flux haemodialysis membranes.The former led to a reduction of initial serum free leptin values to 76+/-17% (P<0.01), whereas bound leptin remained unaffected. CONCLUSION: Serum-free leptin levels are elevated in ESRD without any apparent effect on body weight. In contrast, serum bound leptin levels remain stable, thus central feedback regulation via the bound form of the hormone may serve as an alternative explanation in the regulation of food intake and energy expenditure in chronic patients on haemodialysis with no apparent nutritional problems.     

Correlation of serum leptin concentrations with body composition and gender in Taiwanese hemodialysis patients without diabetes

OBJECTIVE: (1) To evaluate the impact of body composition and gender on serum leptin concentration in hemodialysis patients. (2) To study which marker of adiposity is most appropriate in Taiwanese hemodialysis patients without diabetes. (3) To compare the nutrition status between nonlean and lean subjects. PATIENTS AND METHODS: Serum leptin concentrations were measured by radioimmunoassay collected in 88 hemodialysis patients without diabetes. Bioimpedance analysis was performed to determine percent fat mass (%FM), lean body mass (LM), and total body water (TBW). Body mass index (BMI) was calculated as weight/height2. Albumin and transferrin were measured by standard laboratory methods. RESULTS: Serum leptin levels were more correlated with percent fat mass (r = 0.697; P < 0.001) than with body fat mass (r = 0.672; P < 0.001) or with BMI (r = 0.594; P < 0.001) in the group as a whole and in each subgroup when analyzed separately by gender. The mean (+/- SD) serum leptin levels were 32.5 +/- 34.3 ng mL(-1) in women subjects and 13.6 +/- 15.5 ng mL(-1) in men subjects (P < 0.001). Multiple regression analysis in all subjects revealed that serum leptin levels were independently affected by percent fat mass and gender. Adiposity corrected serum leptin, such as leptin/BMI, leptin/percent fat mass, and leptin/body fat mass was significantly different between sexes (P < 0.001). The significantly higher serum leptin concentrations in women than in men were observed in obese subjects with BMI > 25 kg/m2 (P < 0.001) as well as nonobese subjects with BMI < 25 kg/m2 (P < 0.05). There were no differences in lean mass and albumin between nonlean and lean subjects. CONCLUSION: Gender and adiposity had impact on serum leptin levels in hemodialysis patients without diabetes. In terms of adiposity, serum leptin levels had stronger correlation with percent fat mass than with body fat mass (FM) or BMI in Taiwanese hemodialysis patients. Steady-state serum leptin levels could serve as valuable clinical markers for the body adiposity in stable hemodialysis patients without diabetes. Protein malnutrition markers and lean mass should be checked in lean subjects for the evaluation of the protein stores of hemodialysis patients.     

Measurement of serum leptin in patients with chronic renal failure on hemodialysis.

BACKGROUND: Leptin, the product of the obese gene, is produced exclusively in fat cells. SUBJECTS, MATERIALS AND METHODS: To evaluate the clinical significance of measuring serum leptin in 56 patients with chronic renal failure on hemodialysis (HD), we measured leptin levels using radioimmunoassay in 34 normal volunteers and in 56 patients on HD. RESULTS: Normal serum leptin averaged 5.7 +/- 0.7 (mean +/- SEM) ng/ml, which correlated significantly (p < 0.001) with the body fat percentage as measured by bioelectrical impedance analysis. Serum leptin in HD patients ranged from 1.3 to 142 ng/ml. The mean serum leptin analyzed after the logarithmic conversion was 5.6 ng/ml, which was not significantly different from the normal control value, although the body fat percentage was significantly lower than normal volunteers. There was a significant (p < 0.01) positive correlation between body fat percentage and serum leptin in both normal controls and HD patients. The slope of the regression curve was steeper in HD patients than in normal controls. CONCLUSION: (1) serum leptin levels to body fat mass are significantly higher in HD patients than controls; (2) the variability is much wider in HD patients; and (3) a significant relation exists between percent body fat and log serum leptin, the relation being steeper in HD patients than in controls.     

Plasma leptin and insulin levels in weight-reduced obese women with normal body mass index: relationships with body composition and insulin.

Obesity is a complex disease with multiple features that has confounded efforts to unravel its pathophysiology. As a means of distinguishing primary from secondary characteristics, we compared levels of fasting plasma leptin and insulin in a cohort of weight-reduced obese women who have attained and maintained a normal BMI for more than 1 year with the levels in cohorts of never-obese and currently obese women. Weight-reduced obese women showed decreased plasma concentrations of leptin and insulin compared with obese women, but these levels remained significantly higher than those of never-obese women. Plasma leptin levels were highly correlated with plasma insulin levels (r = 0.60, P < 0.001). To further explore relationships with body composition, total body fat was determined by dual-energy X-ray absorptiometry and body fat distribution by computed tomography in subsets of these groups. Weight-reduced obese women had a significantly greater percent body fat and subcutaneous abdominal fat mass than did the never-obese women, and these were highly correlated with plasma leptin (r = 0.90, P < 0.001, and r = 0.52, P < 0.001, respectively). In these weight-reduced obese women, visceral fat mass was similar to that of the never-obese. The insulin sensitivity index and first-phase insulin response were also comparable. These results demonstrate that higher leptin levels in weight-reduced obese women are related to the higher total fat and particularly the subcutaneous fat masses. Normalization of visceral fat mass in the weight-reduced obese was accompanied by normalization of insulin sensitivity index and first-phase insulin response. This study suggests that increases in plasma leptin and insulin in obesity are secondary features of the obese state.     

Serum leptin correlates in infertile oligozoospermic males

Leptin is an adipocyte-secreted protein that participates in the regulation of energy homeostasis. Eighty men were investigated; fertile normozoospermia as a control (n = 30) and infertile oligozoospermia (n = 50). The patients underwent estimation of body weight (kg), height (cm), calculation of body mass index (BMI), semen analysis, serum leptin and testosterone hormones. Mean body weight was significantly higher in infertile oligozoospermia compared with controls. Mean height, BMI and serum testosterone levels showed nonsignificant differences between the two groups. Infertile oligozoospermia had significantly higher mean serum leptin level than controls (mean +/- SD; 6.88 +/- 8.65, 16.3 +/- 13.98 ng ml(-1), P < 0.01). Serum leptin demonstrated significant positive correlation with age, body weight, BMI and significant inverse correlation with serum testosterone. It had nonsignificant correlation with the height and sperm concentration. These results are suggestive of a link between the adipocyte derived hormone, leptin and male reproduction.     

Common genetic variations in CCK, leptin, and leptin receptor genes are associated with specific human eating patterns

Obesity has a heritable component; however, the heterogeneity of obesity complicates dissection of its genetic background. In this study, we therefore focused on eating patterns as specific traits within obesity. These traits have a heritable component; genes associated with a specific eating pattern have not yet been reported at the population level. In this study, we determined whether genetic variations in cholecystokinin (CCK) and leptin genes underlie specific eating patterns. We selected obese individuals showing extreme snacking behavior or use of excessive portion sizes from a large population-based sample (n = 17,357) from the Prospect-EPIC (European Prospective Study into Cancer and Nutrition) study. Using allele-specific PCRs, we tested several single nucleotide polymorphisms in the candidate genes and performed haplotype analysis. Obese carriers of common allelic variations in leptin or the leptin receptor gene had an increased risk to display extreme snacking behavior. In contrast, obese carriers of common allelic variations in CCK had an increased risk to eating increased meal sizes. In conclusion, we identified common allelic variants specifically associated with distinctly different eating patterns, namely extreme snacking behavior or excessive portion size.     

A possible role for leptin in normo- or hypoparathyroid uremic bone in postmenopausal dialysis women

Leptin has been proposed to be a key molecule involved in energy regulation. Based on the generally acknowledged concept that a heavier person has a higher bone density, leptin is thought to be potentially involved in bone metabolism. Serum leptin, various bone markers, and bone mineral density (BMD) were studied in 51 dialysis patients (26 men and 25 women). The serum concentrations of leptin in dialysis patients ranged from 0.7 to 10.4 ng/ml (mean 3.2 ± 2.1 ng/ml) for males and from 1.4 to 44.6 ng/ml (mean 11.8 ± 10.4 ng/ml) for females. There was a good correlation between the body mass index (BMI) and leptin concentration in both male and female patients (P < 0.05). Serum leptin levels also correlated well with the age-adjusted z-score for BMD (P < 0.02) and were inversely correlated with levels of the carboxy-terminal propeptide of type I procollagen (P < 0.05) in females patients, but not in male patients. In conclusion, these results suggest an actual contribution of serum leptin in maintaining bone density in postmenopausal female dialysis patients. Received: April 4, 2000 / Accepted: September 21, 2000     

The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations : distinct metabolic effects of two fat compartments

Obesity is associated with insulin resistance, particularly when body fat has a central distribution. However, insulin resistance also frequently occurs in apparently lean individuals. It has been proposed that these lean insulin-resistant individuals have greater amounts of body fat than lean insulin-sensitive subjects. Alternatively, their body fat distribution may be different. Obesity is associated with elevated plasma leptin levels, but some studies have suggested that insulin sensitivity is an additional determinant of circulating leptin concentrations. To examine how body fat distribution contributes to insulin sensitivity and how these variables are related to leptin levels, we studied 174 individuals (73 men, 101 women), a priori classified as lean insulin-sensitive (LIS, n = 56), lean insulin-resistant (LIR, n = 61), and obese insulin-resistant (OIR, n = 57) based on their BMI and insulin sensitivity index (S(I)). Whereas the BMI of the two lean groups did not differ, the S(I) of the LIR subjects was less than half that of the LIS group. The subcutaneous and intra-abdominal fat areas, determined by computed tomography, were 45 and 70% greater in the LIR subjects (P < 0.001) and 2.5- and 3-fold greater in the OIR group, as compared with the LIS group. Fasting plasma leptin levels were moderately increased in LIR subjects (10.8 +/- 7.1 vs. 8.1 +/- 6.4 ng/ml in LIS subjects; P < 0.001) and doubled in OIR subjects (21.9 +/- 15.5 ng/ml; P < 0.001). Because of the confounding effect of body fat, we examined the relationships between adiposity, insulin sensitivity, and leptin concentrations by multiple regression analysis. Intra-abdominal fat was the best variable predicting insulin sensitivity in both genders and explained 54% of the variance in S(I). This inverse relationship was nonlinear (r = -0.688). On the other hand, in both genders, fasting leptin levels were strongly associated with subcutaneous fat area (r = 0.760) but not with intra-abdominal fat. In line with these analyses, when LIS and LIR subjects were matched for subcutaneous fat area, age, and gender, they had similar leptin levels, whereas their intra-abdominal fat and insulin sensitivity remained different. Thus, accumulation of intra-abdominal fat correlates with insulin resistance, whereas subcutaneous fat deposition correlates with circulating leptin levels. We conclude that the concurrent increase in these two metabolically distinct fat compartments is a major explanation for the association between insulin resistance and elevated circulating leptin concentrations in lean and obese subjects.     

A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls

Mutations in the leptin gene lead to rare obese syndromes of Mendelian inheritance in humans and rodents. However, no relevant mutations are found in the coding region of leptin gene DNA in patients with common multifactorial obesity. These obese patients tend to have an elevation of serum leptin proportional to their adiposity but with a rather wide dispersion of leptin levels for a given body fat content, which in part is attributable to sexual dimorphism. The current study, performed in two independent Caucasian cohorts of obese girls, shows that a frequent promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and body fatness. Girls of comparable adiposity have different circulating leptin levels, depending on their genotype at this locus. Girls with the -/- Lep -2,549 genotype have 25% lower mean leptin levels than the girls with other genotypes, as reflected by differences in the regression slopes of leptin-to-fat mass. Therefore, genetic factors related to the leptin gene may be important in defining the set point of obese individuals (i.e., the circulating leptin level for a given degree of body fatness). This definition may be of both physiological and therapeutic relevance, although a phenotypic association with an individual single-nucleotide polymorphism is not sufficient to assign function to this particular nucleotide site.     

Leptin and Insulin Action in Severely Obese Women

Background: The authors investigated the interrelationships between the components of the metabolic syndrome in severe obesity. Methods: In non-diabetic, severely obese women, the degree of obesity (BMI), the insulin sensitivity (from the Homeostatic Model of Assessment, HOMA), the serum leptin concentration and the presence of dyslipidemia and arterial hypertension were evaluated. Results: In insulin-resistant patients, an overall impaired metabolic status and a greater cardiovascular risk were observed, while serum leptin concentration was higher than in the insulin-sensitive ones. Leptin levels and HOMA data correlated independent of BMI findings, while the presence of dyslipidemia and hypertension was unrelated to the other metabolic syndrome factors. Conclusion: In severely obese women, although other factors independently intervene, serum leptin has a role in developing the metabolic syndrome.     

Perioperative response of leptin and the tumor necrosis factor alpha system in morbidly obese patients. Influence of cortisol inhibition by etomidate

BACKGROUND: Leptin, tumor necrosis factor alpha (TNFalpha) and soluble TNFalpha receptors are secreted by the adipose tissue. Surgery induces a complex cytokine and neurohormonal response. The aim of our study was to investigate the perioperative response of leptin and the TNFalpha system in morbidly obese patients submitted to gastroplasty, and the possible involvement of cortisol in their responses. METHODS: Serum cortisol, adrenocorticotropic hormone (ACTH), leptin, TNFalpha and soluble TNFalpha receptor I were measured in 22 morbidly obese women (11 anesthetized with thiopental and 11 with etomidate, a well known inhibitor of cortisol synthesis). Samples were collected before anesthesia induction, just before surgical incision, and 2, 4, 6, 12, 24 and 48 h after the start of surgery. RESULTS: Baseline serum leptin correlated with body mass index (r=0.567, P=0.007). Baseline serum leptin and TNFalpha were higher than normal. Cortisol release was inhibited in the etomidate group with a subsequent higher stimulation of ACTH release. A statistically significant decrease in serum leptin levels was observed in both groups at 2, 4, 6 and 48 h, compared with basal values. A similar decrease in serum TNFalpha levels was observed in both groups, but the decrease reached significance only in the etomidate group. Serum soluble TNFalpha receptor I did not decrease. No differences were found between the two groups in leptin, TNFalpha or soluble TNFalpha receptor I concentrations at any time. CONCLUSION: Serum leptin and TNFalpha levels decrease in obese patients during gastroplasty. Transitory inhibition of cortisol release does not alter this response.     

Peritoneal clearance of leptin in CAPD patients: impact of local insulin administration.

INTRODUCTION: The ob gene product leptin is secreted by fat cells and the serum leptin levels reflects the body fat content. Markedly elevated serum leptin levels have been reported in patients with chronic renal failure. The aim of the present study was to assess if the dialysate leptin levels in peritoneal dialysate are similar to what can be expected from passive diffusion or if intraperitoneal synthesis of leptin may occur. METHODS: We studied 39 patients (20 males), mean age 54+/-12 years, who had been treated with peritoneal dialysis for 17+/-12 months. Ten of the patients were diabetics of which seven used intraperitoneal insulin. A 24-h collection of dialysate was performed and dialysate and fasting blood samples were analysed for leptin, albumin and beta2-microglobulin, and the peritoneal clearances (PCl) were calculated for these solutes. RESULTS: Serum leptin (mean 47+/-76, range 3-350 ng/ml) was related to body mass index (r=0.35, P<0.05). In multiple regression analysis, serum leptin also correlated to serum TNF-alpha. Although dialysate leptin levels correlated to serum leptin, they were higher than expected from the molecular weight of 16 kD. PCl of leptin was 1.3 ml/min (range 0.2-5.9 ml/min), which was 1.6 times higher than expected from the molecular weight of leptin and PCl for albumin and beta2-microglobulin, not taking the protein binding of leptin into account. A strong correlation was found between PCI for albumin and beta2-microglobulin (r = 0.68, P < 0.0001) but neither PCl albumin, nor PCl beta2-microglobulin correlated to PCI leptin. The PCl of leptin was markedly higher in diabetics using intraperitoneal insulin (n = 7) compared to the other 32 patients (2.6+/-2.0 vs 1.1+/-0.7 ml/min, P<0.05). CONCLUSION: Serum leptin is locally produced in the peritoneal cavity, and intraperitoneal insulin enhances local production of leptin.     

肝癌患者血清瘦素、胰岛素的水平测定及相关性分析

目的探讨瘦素、胰岛素在原发性肝癌及肝硬化患者中的变化。方法采用放射免疫分析法和电化学发光免疫法检测70例肝癌患者、30例肝硬化患者及30例健康者的血清瘦素、胰岛素水平并进行比较分析。结果肝癌及肝硬化患者较正常对照组血清瘦素、胰岛素显著升高,体重指数（body mass index,BMI）显著降低;BMI、胰岛素和性别均为影响肝癌患者血清瘦素浓度的显著因素。结论瘦素、胰岛素可能参与了肝癌及肝硬化患者营养不良的发生。     

Obesity and screening PSA levels among men undergoing an annual physical exam

BACKGROUND: Prior reports suggest that obesity is inversely associated with screening prostate-specific antigen (PSA) levels and may reduce screening sensitivity. METHODS: We evaluated data on 10,623 men screened for prostate cancer during an annual physical examination program administered by EHE International, Inc., between 1/1/2004 and 6/30/2006. Of these, 3,623 men returned for additional physical exams during this period. We used multivariate linear regression analyses to determine whether higher BMI was inversely associated with PSA, and whether BMI, or change in BMI, was associated with change in PSA levels over time. We also developed a theoretical model for the effect of obesity on PSA levels in which increased plasma volume in the obese dilutes PSA levels. RESULTS: After control for age and race/ethnicity, higher BMI was associated with lower PSA levels; men with a BMI > or =40 had a geometric mean PSA level 0.14 ng/ml lower than men with a BMI <25 (P < 0.001). Prospectively, BMI at initial screening and change in BMI over 2 years were not associated with change in PSA or PSA velocity. Our theoretical model accurately predicted observed PSA levels and suggests that a screening PSA of 4.0 ng/ml in normal weight and overweight men corresponds to 3.5 ng/ml in obese men and 3.1 ng/ml in morbidly obese men. CONCLUSION: Across the study population, increased BMI was significantly inversely associated with lower PSA. Based on a theoretical model in which increased plasma volume in the obese dilutes PSA levels we propose new cut-points for a positive screening test.