Genetics of leptin and obesity: a HuGE review

Leptin is an important regulator of the mass of adipose tissue and of body weight; it operates by inhibiting food intake and stimulating energy expenditure. Some polymorphic genes involved in the regulation of leptin-the leptin gene (LEP A19G), the leptin receptor gene (LEPR Q223R, K109R, and K656N), and the peroxisome proliferator-activated receptor-gamma gene (PPARG P12A and C161T)--have been investigated as possible factors associated with obesity. Allelic frequencies of these polymorphisms show ethnic variation. The authors performed a meta-analysis of the available data on the association between these polymorphisms and obesity based on case-control studies. Odds ratios and 95% confidence intervals for obesity associated with leptin polymorphisms were calculated by using both fixed- and random-effects models. Results suggest no evidence of association between the genes under study and obesity. The lack of association could be due to the complex pathogenesis of obesity, which involves a number of genetic and environmental factors. Large studies including testing of multiple genes in both obese and lean subjects, with epidemiologic data on dietary habits in different ethnic groups, are necessary to better understand the role of leptin in regulating weight in human populations.     

The Association between Peptide Hormones with Obesity and Insulin Resistance Markers in Lean and Obese Individuals in the United Arab Emirates

Peptide hormones play a crucial role in body weight and glucose homeostasis. In this study, we aimed to explore this association and recruited 43 obese and 31 age- and sex-matched lean participants. We assessed their body mass index (BMI), waist circumference (WC), waist-to-height ratio (WtHR), percentage body fat (PBF), fasting blood levels of peptide hormones (GLP-1, GLP-2, insulin, leptin, ghrelin, CCK, and PYY), fasting blood sugar (FBS), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). We tested the associations between peptide hormones and markers of obesity and insulin resistance (IR) by using the Independent-Samples t-test and Mann-Whitney U test, partial correlation, and logistic regression. FBS, insulin, HOMA-IR, GLP-1, GLP-2, and leptin were significantly higher in the obese group; ghrelin and CCK were significantly higher in lean participants, and no difference was seen for PYY. Controlling for BMI, GLP-1 was positively correlated with WtHR, while ghrelin was inversely correlated with WtHR. GLP-1 was correlated with HOMA-IR. GLP-1 was associated with obesity and IR markers in the regression model. Our results show that obese and lean adults display significant differences in plasma peptide hormone levels. GLP-1 levels were independently associated with markers of obesity and IR. Restoring the appetite hormone balance in obesity may represent a potential therapeutic target.     

Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain

There are no good genetic markers for incorporating the study of genetic susceptibility to obesity in epidemiological studies. In animal models, the leptin (LEP) and the leptin receptor (LEPR) genes have been shown to be very important in obesity because leptin functions as a negative feedback signal in regulating body-weight through reducing food intake and stimulating energy expenditure. In humans, several polymorphisms in these genes have been described. However, their association with obesity is still very controversial because there are no good case-control studies designed to specifically test this association. Our objective has been to conduct a population-based case-control study to estimate the risk of obesity arising from the −2548G > A and Q223R polymorphisms in the LEP and LEPR genes, respectively. 303 obese cases (101 men and 202 women) and 606 controls (202 men and 404 women) were selected from a Spanish Mediterranean population. Genetic, clinical and life-style characteristics were analyzed. No association was found between the −2548G > A polymorphism and obesity. However, the Q223R variant was significantly associated with obesity in a recessive model, the RR genotype being more prevalent in controls than in obese subjects. The inverse association between the Q223R polymorphism and obesity (OR = 0.62; 95% CI: 0.39–0.99) remained significant even after additional adjustment for education, tobacco smoking, alcohol, physical activity, origin of the obese patient, and the −2548G > A polymorphism in the LEP gene (OR = 0.54; 95% CI: 0.32–0.89). In conclusion, the −2548G > A polymorphism is not a relevant obesity marker in this Mediterranean population, although Q223R does seen to be so.     

Functional status and emotional well-being, dietary intake, and physical activity of severely obese subjects

OBJECTIVE: Analyze functional status and emotional well-being, energy and nutrient intake, and physical activity in sibling pairs raised together in the same family. DESIGN: One sibling classified as severely obese (body mass index > or = 35) and the other sibling as normal weight (body mass index < or = 27). SUBJECTS: From January 1994 through December 1996 at the Cardiovascular Genetics Research Clinic of the University of Utah School of Medicine, 145 sibling pairs (n = 290) were selected from a population-based, family history database or a hospital-based, very-low-energy weight-loss program. STATISTICAL ANALYSIS PERFORMED: Repeated-measures analysis of variance tested for differences between severely obese and normal-weight siblings. RESULTS: All functional status and emotional well-being scores (poorer perceived health) were significantly lower in severely obese siblings compared with normal-weight siblings. The severely obese siblings had a higher percentage dietary fat intake (3% higher) and total energy intake (more than 350 kcal higher), and lower weight-adjusted total energy intake (almost 10 kcal/kg lower) and activity energy expenditure (3.5 kcal/kg lower), compared with normal-weight siblings. Thus, environmental influences such as energy and nutrient intake and physical activity are highly related to severe obesity. APPLICATIONS: Previously shared environment of severely obese and normal-weight siblings raises questions about whether strong environmental influences or genetic predisposition account for the differences in sibling weight. When counseling individuals or families with a history of severe obesity, dietetics practitioners should be familiar with the potential for strong genetic factors and related environmental influences. In addition, dietitians should be prepared to offer a flexible approach to physical exercise as well as provide additional behavioral support.     

Sequence variation within the neuropeptide Y gene and obesity in Mexican Americans

OBJECTIVE: Recently, we reported evidence for linkage between neuropeptide Y (NPY) and both obesity and several obesity-related quantitative measures in a sample of Mexican Americans from Starr County, Texas. The purpose of this study was to investigate putative variation within the coding and promoter regions of NPY. RESEARCH METHODS AND PROCEDURES: Five young, obese individuals (body mass index [BMI] 33 to 45 kg/m2, age 14 to 30 years); five adult, lean individuals (BMI 20 to 26 kg/m2, age 39 to 65 years); and five sibling pairs sharing no alleles that were identical by descent at a marker locus proximal to NPY were selected for fluorescence-based sequencing of approximately 1100 base pairs (bp) immediately 5' from the start site and all four exons of NPY. We identified a total of eight variant sites, including a 2-bp insertion/deletion (I/D) within a putative negative regulatory region (-880I/D) and a 17-bp deletion at the exon 1/intron 1 junction (69I/D). The -880I/D and 69I/D variants were typed in a separate random sample of Mexican Americans (N = 914) from Starr County, Texas. RESULTS: Analyses of variance resulted in a significant association between -880I/D and waist-to-hip ratio (p = 0.041) in the entire sample and between -880I/D and BMI (p = 0.031), abdominal circumference (p = 0.044), and waist-to-hip ratio (p = 0.041) in a non-obese subsample (BMI < 30 kg/m2, n = 594). The 69I/D variant was observed in only one pedigree and does not appear to segregate with obesity within this pedigree. DISCUSSION: This study reports newly identified common human sequence variation within the regulatory and coding sequence of NPY. Several variants were observed, and of those tested, the -880I/D promoter region variant may influence body fat patterning in non-obese individuals but does not appear to play a major role in the etiology of common forms of obesity in this population.     

Expression levels of genes likely involved in glucose-sensing in the obese Zucker rat brain

It has been suggested that certain cells in the brain, like pancreatic beta-cells, use glucose transporter-2 (GLUT-2), glucokinase and glucagon-like peptide-1 receptor (GLP-1R) to sense glucose in the service of multiple aspects of energy balance. The obese Zucker rat displays numerous disturbances in energy homeostasis and may provide a model of dysfunctional expression of genes related to nutrient control systems. Using real-time RT-PCR we measured gene expression for three of the pancreatic glucose-sensing markers and neuropeptide Y (NPY) in the medial, lateral hypothalamus and hindbrain of lean and obese Zucker rats of both genders. Additionally, we measured circulating levels of glucose, leptin, insulin, corticosterone and glucagon. The results indicate that GLUT-2 mRNA expression is decreased, whereas glucokinase is increased in the hindbrain of obese rats. NPY mRNA level is significantly higher, whereas GLP-1R is significantly lower in the medial hypothalamus in obese individuals. Gender-related differences were found in the hindbrain and medial hypothalamus for GLUT-2 and in the lateral hypothalamus for GLP-1R and they may be related to the fact that the female Zucker rats do not develop diabetes as readily as males. Furthermore, the hindbrain may be an important site for glucose-sensing where major phenotypic changes occur for glucose-sensing genes expression.     

瘦素受体Gln223Arg基因多态性与肥胖关系的研究

目的 研究瘦素受体Gln223Arg基因多态性与肥胖的关系。方法 2004年在山西省盂县选取一组人群，凋查其心血管病危险因素，同时抽血检测瘦素受体Gln223Arg基因多态性的基因型，并分析Gln223Arg基因多态性与肥胖的关系。结果 该组人群GG、GA及AA的基因型频率分别为0．7679、0．2171和0．0151；G和A等位基因频率分别为0．8764和0．1236。基因型频率分布符合Hardy-Weinberg平衡（P=0．934）。单因素分析结果表明携带A等位基因的研究对象具有更高的体重（63．2kg vs．61．9kg；P=0．0307）和体重指数（24．4kg／m^2 vs．24．1kg／m^2；P=00898）；在调整年龄、性别、体力活动和膳食之后，携带A等位基因者仍然具有较高的体重指数（24．5kg／m^2 vs．24．1kg/m^2；P=0．0396）和肥胖患病率（OR=1．30，95％CI：0．957～1．767；P=0．0935）。结论 瘦素受体Gln223Arg基因多态性与肥胖可能有关。     

血清网膜素-1水平与儿童非酒精性脂肪肝的关系

目的 探索网膜素-1与儿童非酒精性脂肪肝(NAFLD)的相关性,为儿童脂肪肝的防治提供参考。方法 将116名肥胖儿童分为肥胖伴脂肪肝组(61名)、肥胖不伴脂肪肝组(55名),同时选择正常体重儿童55名作为对照组,对每位儿童进行身高、体重、腰围、血压等测量,并行血脂、血糖、肝功等化验,留取静脉血清标本测血清胰岛素、网膜素-1、瘦素、脂联素水平等,判断三组间指标差异及网膜素-1与其他指标相关性。采用Logistics回归判断有无脂肪肝与其他指标的关系,采用ROC曲线评估腰围、体重指数(BMI)、网膜素-1水平对儿童脂肪肝诊断标准有无价值。结果 血清网膜素-1在肥胖伴脂肪肝患儿中水平较另两组水平低(P<0.05)。矫正年龄及腰围后网膜素-1与有无合并脂肪肝、瘦素/脂联素(LAR)、低密度脂蛋白胆固醇(LDL-C)为负相关,与脂联素呈正相关(P<0.05)。Logistics回归分析发现BMI、胰岛素抵抗指数(HOMA-IR)为脂肪肝的危险因素,网膜素-1为脂肪肝的保护因素。腰围、BMI、血清网膜素-1水平对儿童脂肪肝诊断有一定价值。结论 血清网膜素-1水平与儿童中心性肥胖、脂代谢紊乱及脂肪肝密切相关,在儿童脂肪肝的发病中有保护作用。     

Early-onset severe obesity due to homozygous p.R105W (c313C> T) mutation in leptin gene in Turkish siblings: Two cases reports

Congenital leptin deficiency (CLD) is a rare cause of monogenic form obesity due to homozygous or compound heterozygous mutations in the LEP gene. To date, nine pathogenic mutations have been reported. In this study, we present are; an 18-year-old morbidly obese girl and a 14-year-old obese brother, both with homozygous mutation in the LEP gene [p.R105W (c313C> T)] and their data after three years of recombinant leptin treatment. To date, few cases of CLD have been reported in the literature. The cases reported here were siblings who were not diagnosed despite presentation at the clinic due to obesity in childhood, and diagnosis was delayed until adolescence. Clinicians need to consider CLD, a monogenic form of obesity in children with early severe obesity onset, especially if they are the child of a consanguineous marriage.     

Relation between plasma leptin and anthropometric and metabolic covariates in lean and obese diabetic and hyperlipidaemic Asian Northern Indian subjects

This study investigated the relationship of plasma leptin to obesity, diabetes and hyperlipidaemia in Asian Northern Indian subjects, considered to have a predisposition to abdominal obesity and metabolic syndrome. A total of 72 subjects, subcategorised into lean and obese healthy subjects, lean and obese Type 2 diabetic and lean and obese non-diabetic hyperlipidaemic subjects were recruited. High leptin values were observed in all obese groups, and obese diabetic patients showed the highest levels. In lean and obese diabetic subjects, plasma leptin did not show any correlation to any index of glycaemia. When all lean and all obese subjects were analysed in two separate groups, body mass index (BMI), percent total body fat, and body density significantly correlated with the plasma leptin levels (p<0.05). Leptin values, when correlated to all variables in all patients taken together, showed the greatest magnitude of correlation with BMI (r=0.64), percent total body fat (r=0.67), and waist circumference (r=0.51). Strong inverse correlation was seen with body density (r=-0.67). Levels of serum insulin did not show any correlation with leptin levels in all subjects combined, and separately in various groups. Multiple linear regression analysis performed in obese, non-diabetic and normolipidaemic subjects, all Type 2 diabetic and all non-diabetic hyperlipidaemic subjects separately showed that percent total body fat is the only significant predictor of plasma leptin concentration in all the 3 groups. The present study suggests that plasma leptin has a strong positive correlation with percent total body fat in Asian Northern Indian subjects. Among other components of metabolic syndrome, only abdominal obesity is weakly correlated to serum leptin levels.     

Relationship of ghrelin and leptin hormones with body mass index and waist circumference in a random sample of adults

OBJECTIVE: To evaluate the relationship of ghrelin and leptin hormones with body mass index (BMI) and waist circumference in a population-based random sample of adult men and women subsequently categorized from normal weight to severely obese based on BMI criteria. The relationship between total ghrelin and leptin was also evaluated. DESIGN: A cross-sectional study was conducted on adults. METHODS: Two-hundred thirty-three men (n=107) and women (n=126) between the ages of 23 and 75 years were randomly selected from a database of over 600,000 adults who had previously participated in a population-based study conducted by the University of Utah Cardiovascular Genetics Program. Items collected included height, weight, waist circumference, and fasting blood samples. Blood samples were later thawed, and plasma leptin and total ghrelin levels were analyzed with radioimmunoassay kits. RESULTS: Leptin levels were directly associated with BMI (r=0.72, P=0.001) and waist circumference (r=0.71, P=0.0001), whereas total ghrelin was inversely associated with BMI (r=-0.39, P=0.001) and waist circumference (r=-0.37, P=0.001). There were also statistically significant linear changes in means across the BMI categories for both hormones. After controlling for BMI and waist circumference, the highly significant correlation of leptin with ghrelin (r=-0.39) was reduced but still significant (r=-0.17, P=0.01). CONCLUSION: Leptin increases and ghrelin decreases were linear over the five BMI categories, suggesting there is no threshold of BMI where the hormone levels change abruptly. There remain other factors beyond current BMI and waist circumference that induce a correlation of these two hormones. Further understanding of the role that each of these hormones has in influencing appetite and body weight may provide insight into mechanisms involved with obesity.     

瘦素及瘦素受体基因多态性与乳腺癌的相关性研究

目的探讨瘦素及其瘦素受体基因多态性与乳腺癌发生的关系。方法采用PCR- RFLP对94例乳腺癌患者、128例健康对照者进行瘦素受体基因Gln223Arg多态性检测;ELISA分析法测定瘦素水平。结果乳腺癌组瘦素受体基因Gln223Arg的GG、GA和AA基因型表达频率分别为69.15%、17.02%和13.83%;等位基因G和A为77.66%和22.34%与对照组82.03%、15.63%和2.34%及等位基因的89.84%和10.16%相比较,差异有统计学意义(P=0.004,P=0.001)。乳腺癌组瘦素水平,腰臀比(WHR)明显高于对照组,差异均有统计学意义(P<0.01,P<0.001)。非条件logislic回归多因素分析表明,瘦素受体基因多态性、瘦素水平及WHR升高,与乳腺癌发生的相关危险度分别为:OR=4.87,95%CI:1.30-18.22,P=0.019;OR=1.53,95%CI:1.13-2.07,P= 0.006;OR=3.68,95%CI:1.34-10.11,P=0.011。结论瘦素受体基因Gln223Arg多态性、瘦素及WHR升高,可能增加乳腺癌发生的风险性。     

瘦素受体基因Gln223Arg多态性与肥胖的关联研究

目的探讨瘦素受体基因多态性与肥胖发生的关系。方法采用PCR-RFLP对502例肥胖患者、400例体重正常者进行瘦素受体基因Gln223Arg多态性检测。结果肥胖组瘦素受体基因Gln223Arg的GG、GA和AA基因型表达频率分别为0.777、0.197及0.026。单因素分析显示携带AA基因型与携带GG基因型相比,发生肥胖的风险为OR=0.478,P=0.043。多因素分析表明,瘦素受体基因多态性、年龄>65岁、吸烟以及口味偏重与肥胖发生的相对危险度分别为:OR=1.36,95%CI:0.999~1.849,P=0.05;OR=0.55,95%CI:0.366~0.825,P=0.004;OR=1.475,95%CI:1.064~2.045,P=0.02;OR=1.506,95%CI:1.042~2.176,P=0.029。结论瘦素受体基因Gln223Arg多态性可能与肥胖发生有关。     

Genetic variation and obesity in Australian women: a prospective study.

OBJECTIVE: A number of candidate genes have been implicated in the pathogenesis of obesity in humans. This study examines associations between longitudinal changes in body mass and composition and the presence of polymorphisms in the beta-3 adrenergic receptor, tumor necrosis factor-alpha, leptin, and leptin receptor (Lepr) in a cohort of Australian women. RESEARCH METHODS AND PROCEDURES: Healthy white Australian women (n = 335) were randomly selected from the Barwon region of Victoria and underwent baseline anthropometry and double-energy X-ray absorptiometry for assessment of body mass and adiposity. These measurements were repeated again at 2-year follow-up. Genomic DNA was extracted and used for polymerase chain reaction-based genotyping of all polymorphisms. RESULTS: The Pro1019Pro Lepr polymorphism was associated with longitudinal increases in body weight (p = 0.02), fat mass (p = 0.05), and body mass index (p = 0.01) in this study, and individuals homozygous for the A allele at this locus had a greater propensity to gain body fat over time. The largest effects on body composition seemed to be in individuals already obese at baseline. Changes in body weight, fat mass, percent body fat, and body mass index over a 2-year period were not associated with genetic variation in the beta-3 adrenergic receptor (Trp64Arg), tumor necrosis factor-alpha promoter, or leptin genes in non-obese or obese women. DISCUSSION: These results suggest that a Lepr polymorphism is involved in the regulation of body mass and adiposity in obese Australian white women, which may have implications for the treatment of obesity in this population.     

Genotype-dependent response to energy-restricted diets in obese subjects: towards personalized nutrition

Obesity is a complex disease, which in many cases appears as a polygenic condition affected by environmental factors (mainly unbalanced dietary patterns and physical inactivity). In this context, the weight loss response to dietary interventions varies widely and predictive factors of successful slimming including those concerned with the individual's genetic make-up are poorly understood. Indeed, a number of genes involved in the regulation of energy expenditure, appetite, lipid metabolism and adipogenesis have been reported to affect the risk of treatment failure in some obese subjects. Some candidate genes for the prognosis of weight loss response related to energy expenditure are those codifying for the adrenergic receptors (ADBRs) and uncoupling proteins (UCPs), while genes related to appetite potentially affected by energy restriction are leptin (LEP), leptin receptor (LEPR), melanocortin pathways genes (MC3R, POMC) and the serotonin receptor. Furthermore, adipogenesis related genes such as peroxisome proliferator-activated receptor (PPAR gamma 2) and genes related to cytokines such as interleukin-6 (IL-6) and lipid metabolism including hepatic lipase (LIPC), perilipin (PLIN) and lipoprotein lipase (LPL) have also been associated to the weight lowering outcome induced by hypocaloric diets. Therefore, this review shows preliminary evidence from human studies that support the existence of a genetic component in the fat reduction process associated to a negative energy balance.     

Leptin levels,leptin receptor gene polymorphisms,and energy metabolism in women

OBJECTIVE: Resting metabolic rate (RMR) is mainly determined by fat-free mass and additionally by age, sex, hormones, and possibly genetic differences. We evaluated whether leptin levels and polymorphisms in the leptin receptor (LEPR) gene were associated with energy expenditure phenotypes. METHODS: RMR, body composition, and leptin levels were measured in 125 overweight and obese women. Three LEPR polymorphisms, Lys109Arg, Gln223Arg, and Lys656Asn, were typed on genomic DNA of another group of 192 women in whom RMR was measured. Fat, protein, and carbohydrate oxidation were calculated for 103 of these subjects. In 38 subjects, glucose-induced thermogenesis was measured over 3 hours. RESULTS: In the first study group, a negative correlation between RMR and leptin levels was found after controlling for fat and fat-free mass. In multiple regression analysis, leptin contributed significantly to RMR, independent of body composition. In the second study group, RMR was not associated with LEPR polymorphisms. Differences in substrate oxidation rates were found among genotypes at the Lys656Asn site. In fasting conditions, Lys656Lys showed a trend to oxidize more carbohydrates and less fat than Asn656 carriers, a trend which became significant after the glucose load when carbohydrate oxidation rate in Lys656Lys was 15% higher than in Asn656 carriers (p = 0.04), and fat oxidation rate was 44% lower (p = 0.02). DISCUSSION: These results suggest that DNA sequence variations in the LEPR gene could affect substrate oxidation. We hypothesize that this might be caused by differences in glucose levels, leading to differences in glucose oxidation rates.     

北京市小学生BMI、腰围与代谢综合征的关系研究

目的 探讨儿童肥胖与代谢综合征(MS)的关系,分析体重指数(BMI)和腰围与MS组分的关系.方法 在北京市海淀区的8所学校选取1 928名7～14岁小学生,测量其身高、体重和各MS组分,分析不同营养状况小学生MS组分的差异.采用多元线性回归和Logistic回归模型,分析BMI、腰围与MS组分的关系.结果 除空腹血糖外,血压、血脂、腰围在不同营养状况小学生之间差异有统计学意义(P＜0.05),表现为肥胖组＞超重组＞体重正常组.不同营养状况小学生高SBP、高TG、低HDL-C、中心性肥胖的检出率差异均有统计学意义(P＜0.01),随BMI增加异常率增高.多元线性回归发现BMI和腰围均与除中心性肥胖外的其他MS组分有独立的相关性;除TC外, “腰围”对于其他MS组分的标化回归系数绝对值略大于“BMI”.除DBP外,对于其他MS组分,BMI与腰围同时升高(超重/肥胖且腰围≥P90)的OR值＞BMI和腰围有且仅有一项偏高(超重/肥胖或腰围≥P90)＞体重正常且腰围正常.结论 儿童肥胖与代谢综合征关系密切,联合应用腰围和BMI有利于评估MS风险.     

肥胖和肥胖抵抗大鼠神经肽Y及其受体基因表达的研究

目的:探讨高脂饲料对大鼠下丘脑神经肽Y(NPY)及其受体Y1、Y2、Y5基因表达的影响及大鼠肥胖易感性差异的机制。方法:36只雌性SD大鼠,按体重随机分为高脂组和对照组,分别给予高脂饲料和基础饲料13w。实验结束时,根据体重将高脂组分为饮食诱导肥胖(DIO)和肥胖抵抗(DIO-R)大鼠,观察各组大鼠体重、内脏脂肪湿重、脂体比、热能摄入量及能量利用率的差异;RT-PCR法测定下丘脑NPY及其受体Y1、Y2、Y5mRNA的表达水平。结果:DIO大鼠体重、内脏脂肪湿重、脂体比、热能摄入量及能量利用率显著高于对照组和DIO-R大鼠,而DIO-R大鼠与对照组相比未见显著性差异;DIO大鼠下丘脑NPY及其受体Y1、Y2、Y5mRNA的表达水平显著高于对照组和DIO-R大鼠,而DIO-R大鼠与对照组相比,除Y2受体mRNA的表达水平显著下降外,其余指标均无显著性差异。结论:高脂饲料诱导下,SD大鼠表现为明显的肥胖易感性差异,下丘脑NPY及其受体的高水平表达可能是导致DIO大鼠热能摄入过多的内在机制之一。     

Leptin and leptin-related gene polymorphisms,obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals

Obesity is a risk factor for complicated influenza A/H1N1 disease and poor vaccine immunogenicity. Leptin, an adipocyte-derived hormone/cytokine, has many immune regulatory functions and therefore could explain susceptibility to infections and poor vaccine outcomes. We recruited 159 healthy adults (50–74 years old) who were immunized with inactivated TIV influenza vaccine that contained A/California/7/2009/H1N1 virus. We found a strong correlation between leptin concentration and BMI (r = 0.55, p < 0.0001), but no association with hemagglutination antibody inhibition (HAI), B-cell, or granzyme B responses. We found a slight correlation between leptin concentration and an immunosenescence marker (TREC: T-cell receptor excision circles) level (r = 0.23, p = 0.01). We found eight SNPs in the LEP/LEPR/GHRL genes that were associated with leptin levels and four SNPs in the PTPN1/LEPR/STAT3 genes associated with peripheral blood TREC levels (p < 0.05). Heterozygosity of the synonymous variant rs2230604 in the PTPN1 gene was associated with a significantly lower (531 vs. 259, p = 0.005) TREC level, as compared to the homozygous major variant. We also found eight SNPs in the LEP/PPARG/CRP genes associated with variations in influenza-specific HAI and B-cell responses (p < 0.05). Our results suggest that specific allelic variations in the leptin-related genes may influence adaptive immune responses to influenza vaccine.     

Gastric pacing for morbid obesity: plasma levels of gastrointestinal peptides and leptin

OBJECTIVE: A gastric pacemaker has been developed to treat morbid obesity. Patients experience increased satiety, the ability to reduce food intake, and a resultant weight loss. However, the mechanism behind the changed eating behavior in paced patients is still under investigation. RESEARCH METHODS AND PROCEDURES: This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m2) treated with gastric pacing. The peripheral blood levels of satiety signals of cholecystokinin (CCK), somatostatin, glucagon-like peptide-1 (GLP-1), and leptin were studied 1 month before gastric pacer implantation, 1 month after implantation, and 6 months after activation of electrical stimulation. Blood samples were drawn 12 hours after fasting and in response to a hypocaloric meal (270 kcal). Patients were followed monthly for vital signs and weight level. RESULTS: Gastric pacing resulted in a significant weight loss of a mean of 10.4 kg (4.4 BMI units). No negative side effects or complications were observed during the treatment. After activation of the pacemaker, meal-related response of CCK and somatostatin and basal levels of GLP-1 and leptin were significantly reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01). DISCUSSION: Gastric pacing is a novel and promising therapy for morbid obesity. Activation of the gastric pacer was associated with a decrease in plasma levels of CCK, somatostatin, GLP-1, and leptin. More studies are necessary to elucidate the correlations between satiety, weight loss, and digestive neuro-hormone changes.