leptin and Diseases-in-Twins

Although rapid globalization of the Westernized way of life is responsible for the large rise in the number of obesity cases (about 1 billion individuals are now overweight or frankly obese), obesity is a typical common multifactorial disease in that environmental and genetic factors interact, resulting in a disease state. There is strong evidence for a genetic component to human obesity: e.g., the familial clustering (the relative risk among siblings being 3-7) and the high concordance of body composition in monozygotic twins. However, the role of genetic factors in many human obesities (referred to as "common obesity" in this review) is complex, being determined by interaction of several genes (polygenic), each of which may have relatively small effects (i.e., they are "susceptibility" genes and work in combination with each other as well as with environmental factors such as nutrients, physical activity, and smoking).

Topics: Adipocytes; Body Weight; Chromosome Mapping; Diseases in Twins; Family Health; Genetic Linkage; Humans; Hypothalamus; Leptin; Models, Biological; Obesity; Polymorphism, Genetic

Obesity is a complex disease resulting from the interaction between a variety of genetic and environmental factors. Research conducted over the past 20 years in the field of genetic epidemiology has contributed to increase our understanding of the genetic basis of obesity. It is now clearly established that overweight and obesity aggregate in families. Studies have shown that the prevalence of obesity is 2 to 8 times higher in families of obese individuals than in the population at large and that the familial risk increases with the severity of obesity. The heritability of the various obesity phenotypes varies considerably depending on the phenotype under study, the nature of familial data and the methods used to compute heritability estimates. Heritability estimates tend to be highest when derived from twin studies (50% à 80%) while they are the lowest when derived from adoption studies (10% à 30%). Several studies have reported the presence of major gene effects for body mass index, body fat and abdominal visceral fat. Finally, there is increasing evidence that shared genetic factors could play a role in determining the covariation between obesity and its major co-morbidities, including blood pressure, insulin resistance, diabetes and dyslipidemia. This genetic covariation is however moderate and accounts for a smaller percentage of the variance compared to the genetic effects reported for each of the phenotypes studied independently.

Topics: Adipose Tissue; Adoption; Biomarkers; Body Mass Index; Diabetes Mellitus; Diseases in Twins; Family Health; Genes, Dominant; Genetic Predisposition to Disease; Genetic Variation; Humans; Leptin; Obesity; Phenotype

Topics: Adipose Tissue; Animals; Diseases in Twins; Genetic Predisposition to Disease; Humans; Leptin; Mice; Mice, Obese; Obesity; Obesity, Morbid; Proteins

Intrauterine growth restriction (IUGR) is a risk factor for developing metabolic syndrome later in life. We explored whether adipokine concentrations in cord blood (CB) and on day 3 (D3) were related to impaired fetal growth and lipids in IUGR twins.. Thirty-six discordant (birth weight [BW] discordance ≥20% calculated in relation to the heavier co-twins) and 42 concordant (BW discordance ≤ 10%) twin pairs were included.. In IUGR twins, both adiponectin/BW and triglyceride (TG) levels were significantly higher, while total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol were lower in CB. On D3, both leptin and HDL-C levels were significantly lower and TG levels were significantly higher in IUGR twins. In the discordant group, the alterations in lipids were not related to any adipokine.. IUGR is related to lower leptin level and proatherogenic lipid profile (higher TG and lower HDL-C), which are not influenced by adipokine at birth.

Topics: Adipokines; Adult; Birth Weight; Diseases in Twins; Female; Fetal Blood; Fetal Development; Fetal Growth Retardation; Humans; Leptin; Lipids; Male; Middle Aged; Pregnancy; Pregnancy, Twin

Siblings born before (BMS) and after (AMS) maternal biliopancreatic diversion (BPD) show differences in the methylome. The objective was to use a sibling-pair design to examine the effects from interpregnancy weight loss as a consequence of maternal bariatric surgery, other than BPD, on the methylome comparing BMS and AMS.. Women with at least one child born before and one after bariatric surgery were identified in Swedish national registers. Whole blood samples from BMS (N = 31) and AMS (N = 31) siblings were collected for epigenetic methylation analysis while maternal information was collected from antenatal medical records.. In total 3,074 genes, with corresponding 23,449 CpG methylation sites, were differently methylated and associated with an overrepresentation of differently methylated CpG sites in genes involved with insulin receptor signaling, type 2 diabetes signaling, and leptin signaling in obesity, while the most significant differently methylated genes were HLA-DQA1, HLA-DQB1, and TSPAN18, when comparing BMS and AMS siblings.. These results suggest that maternal bariatric surgery, with subsequent weight loss between pregnancies, is associated with alterations in the methylome of genes involved in insulin receptor signaling, type 2 diabetes signaling, and leptin signaling in obesity in a comparison of BMS and AMS siblings.

Topics: Adult; Bariatric Surgery; Biliopancreatic Diversion; Child; Child, Preschool; Diabetes Mellitus, Type 2; Diseases in Twins; DNA Methylation; Female; HLA-DQ alpha-Chains; HLA-DQ beta-Chains; Humans; Infant; Infant, Newborn; Inflammation; Leptin; Male; Obesity; Pregnancy; Sweden; Tetraspanins

Chronic treatment with valproate (VPA) is commonly associated with weight gain, which potentially has important health implications, in particular increased central fat distribution. We utilized a VPA-discordant same-sex, twin and matched sibling pair study design to primarily examine for differences in fat distribution between patients with epilepsy treated with VPA compared to their matched twin or sibling control. Weight, blood pressure, and leptin levels were assessed.. Height, weight, waist and hip measurements, exercise, blood pressure (BP), and serum leptin levels were measured. Body composition was measured using dual-energy x-ray absorptiometry (DXA). Abdominal fat was expressed as a percentage of the abdominal region (AFat%); and of whole body fat (WBF); (AFat%WBF). Mean within-pair differences were assessed (VPA-user and nonuser). Restricted maximum likelihood (REML) linear mixed model analysis was fitted to examine associations of anthropometrics, zygosity, gender, menopausal status, VPA dose and duration, with weight and AFat%.. We studied 19 pairs of VPA-discordant, gender-matched (five male, 14 female) twins and siblings. Mean (standard deviation, SD) duration of therapy for VPA users was 11.0 (7.4) years. There were no statistically significant within-pair differences in age, height, weight, body mass index (BMI), BP, leptin level, WBF, AFat%, or AFat%WBF. For pairs in which VPA-user was treated for >11 years there were statistically significant mean within-pair differences in AFat%, (+7.1%, p = 0.03, n = 10 pairs), mean BP (+11.0 mm Hg, p = 0.006, n = 8 pairs); but not in AFat%WBF. VPA duration was positively associated with weight (estimate +0.98 kg/per year of VPA, p = 0.03); VPA treatment duration and dose were not significantly associated with AFat%.. This study demonstrated a relationship between long-term VPA use and abdominal adiposity (AFat%), which could have significant health implications. We recommend ongoing monitoring of weight, BMI, and blood pressure for patients taking VPA.

Topics: Abdominal Fat; Absorptiometry, Photon; Adult; Anticonvulsants; Blood Pressure; Body Composition; Body Fat Distribution; Diseases in Twins; Epilepsy; Female; Humans; Leptin; Male; Sex Factors; Siblings; Twins, Dizygotic; Twins, Monozygotic; Valproic Acid; Weight Gain

Severely growth-discordant monochorionic (MC) twins offer a unique opportunity to study fetal and placental growth based on a similar genetic background and maternal host environment where the healthy twin serves as an ideal control. Differences in development of MC twins may therefore be due to differential epigenetic regulation of genes involved in placental development and function. Growth-discordant twins are known for abnormal angio-architecture in the placenta of the smaller twin. Since the reasons for this phenotype are mostly unknown this study was aimed to investigate the expression and regulation of genes known to be involved in angiogenesis. We studied 10 severely growth-discordant MC twin placentas (birthweight difference ≥20%) without twin-twin-transfusion syndrome and 5 growth-concordant MC twin placentas. Growth-discordant twin placentas were phenotyped by histology. Placental mRNA expression of 88 angiogenesis-related genes was measured by PCR array. ELISA assay and immunohistochemistry were used to confirm PCR results. EpiTYPTER for DNA methylation was used to determine if methylation ratios were responsible for differential gene expression. The PCR array analysis showed significant mRNA up-regulation in the placental share of the smaller twin for several genes. These included leptin (24.6-fold, P = 0.017), fms-like tyrosine kinase 1 (Flt1, 2.4-fold, P = 0.016) and Endoglin (Eng, 1.86-fold, P = 0.078). None of the other 84 angiogenesis-related genes showed significant differences. ELISA confirmed significantly increased leptin protein expression (49.22 versus 11.03 pg/ml, P = 0.049) in the smaller twin of the discordant growth cohort. Leptin expression in smaller twins' placentas was associated with elevated DNA methylation of the leptin promotor region suggesting the inhibition of binding of a transcriptional activator/inhibitor in that region. We attempted to overcome the limitation of sample size by careful patient selection. We minimized any bias in placental sampling by random sampling from two different sites and by avoiding sampling from areas with grossly visible abnormalities using a standardized sampling protocol. In conclusion, the smaller twin's placenta is characterized by differentially increased gene expressions for Flt1 and Eng mRNA that may be causally associated with the villous pathology driven by abnormal feto-placental angiogenesis. The substantial up-regulation of leptin mRNA may be epigenetically conferred and relev

Topics: Diseases in Twins; Epigenesis, Genetic; Female; Fetal Development; Fetal Growth Retardation; Gene Expression Regulation; Humans; Infant, Newborn; Leptin; Male; Placenta; Pregnancy; Pregnancy, Twin; Twins, Monozygotic

The aim of this study was to investigate the levels of three adipocytokines: leptin, adiponectin and adipsin, in serum and cerebrospinal fluid (CSF) of twins discordant for multiple sclerosis (MS). Adipose tissue is an important component connecting immune system and several tissues and organs including CNS. Fat cells produce adipocytokines, which seem to have a role in various autoimmune disorders including MS.. Plasma samples were collected from twelve twins and CSF samples from four twins discordant for MS. The concentrations of interleukine (IL)-6, adiponectin, adipsin and leptin in plasma and CSF samples were determined by enzyme immuno assay.. A significant difference was seen in the adipocytokine levels in CSF samples. Twins with MS had higher concentrations of adiponectin (P = 0.039) and adipsin (P = 0.039), than their asymptomatic co-twins.. As adiponectin and adipsin levels in CSF did not correlate with their levels in plasma, it seems that there could be a secondary intrathecal synthesis of these adipocytokines in MS.

Topics: Adiponectin; Adult; Complement Factor D; Diseases in Twins; Female; Finland; Humans; Immunoenzyme Techniques; Interleukin-6; Leptin; Male; Middle Aged; Multiple Sclerosis; Twins, Dizygotic; Twins, Monozygotic

To estimate common and distinct genetic influences on a panel of obesity-related traits and serum leptin level in adults. In a cross-sectional study of 625 Danish, adult, healthy, monozygotic, and same-sex dizygotic twin pairs of both genders, we carried out detailed anthropometry (height, weight, waist and hip, and skin-fold thickness, body composition assessment by bioimpedance (fat mass and fat-free mass), and measurement of serum leptin level. Bivariate variance component analyses estimated the additive genetic correlations between these measurements. The genetic correlations between the traits for overall fatness (BMI and fat mass index, kg/m(2)) were 0.94 in men and 0.98 in women, and their correlations with the various local fatness measures ranged from 0.49 to 0.83 in men and from 0.70 to 0.87 in women. The correlations between the truncal measures (waist circumference and truncal skin folds) and between the peripheral measures (hip circumference and peripheral skin folds) were 0.57 and 0.47 in men and 0.71 and 0.70 in women, respectively. The correlations between the truncal and peripheral measures ranged between 0.49 and 0.72 in men and between 0.61 and 0.82 in women. For leptin vs. the various measures of overall and local fatness the correlations ranged from 0.54 to 0.74 in men and from 0.48 to 0.75 in women. All correlations were significantly <1.00. The study supports control of overall fat mass and peripheral and truncal fat mass by both shared and different genetic components, which suggests that it is important to distinguish between the different phenotypes in the search for genes involved in the development of obesity.

Topics: Adipose Tissue; Adult; Body Composition; Body Mass Index; Body Weight; Cross-Sectional Studies; Denmark; Diseases in Twins; Environment; Female; Humans; Leptin; Male; Middle Aged; Obesity; Phenotype; Skinfold Thickness; Twins, Dizygotic; Twins, Monozygotic; Waist Circumference; Young Adult

Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G>A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins.. SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models.. The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465-2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P(additive)=0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P(additive)=0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P=0.014). G allele carriers of the LEP 19G>A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l(-1); P(recessive)=0.013).. This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G>A SNP affect HDL cholesterol levels.

Topics: Adult; Birth Weight; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diseases in Twins; Female; Genetic Predisposition to Disease; Genotype; Humans; Infant, Newborn; Leptin; Male; Phenotype; Polymorphism, Single Nucleotide; Prospective Studies; Receptors, Leptin; Risk Factors; Twins, Dizygotic; Twins, Monozygotic; Young Adult

Singleton infants with intrauterine growth restriction have an adaptive hormonal profile characterized by decreased levels of IGF-1, IGF-2, IGFBP-3 and insulin and elevated levels of IGFBP-1 and IGFBP-2. This study examined the association between cord serum levels of six growth factors and anthropometric features at birth in twins in order to determine the intrauterine growth factor interactions and to characterize the specific hormonal profile of small discordant twins.. Prevalent case-control study.. Twenty pairs of discordant twins (5 monozygotic, 15 dizygotic) and 20 pairs of concordant twins (6 monozygotic, 14 dizygotic) matched for gestational age.. Cord blood levels of IGF-1, IGF-2, IGFBP-1, IGFBP-3, insulin, leptin and anthropometric measurements at birth. Intra- and inter-pair differences and correlation coefficients were calculated, and the data were fitted to multivariate regression models.. In both discordant and concordant groups, the smaller twins had a significantly lower level of IGF-1 (P < 0.03) and significantly higher level of IGFBP-1 (P < 0.02) than their larger cotwins. IGFBP-1 was inversely correlated with IGF-1 (P < 0.05). Insulin levels were significantly higher in the smaller discordant than the smaller concordant twins (P < 0.001) and in the larger discordant than the larger concordant twins (P < 0.004). Among the monozygotic twins, the leptin level was significantly higher in the larger discordant than the larger concordant twins (P < 0.025). Percentage birth weight discordancy was statistically correlated with twin-pair differences in IGF-1 and IGFBP-1.. Of the six factors studied, IGF-1 appears to be the main indicator of intrauterine growth. Twin discordancy may involve compensatory rather than adaptive mechanisms or a multihormone relative resistance syndrome.

Topics: Birth Weight; Case-Control Studies; Diseases in Twins; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Immunoradiometric Assay; Infant, Newborn; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Leptin; Pregnancy; Radioimmunoassay; Regression Analysis; Twins, Dizygotic; Twins, Monozygotic

Polycystic ovary syndrome (PCOS) is a common endocrinopathy with symptoms such as obesity, insulin resistance and hyperandrogenemia. PCOS might be the result of a genetic disorder. Genetic discrepancy in the production of leptin, a product of the obesity gene, may lead to various endocrinopathies such as PCOS. The objective of this study was first, to ascertain the incidence of PCOS, using the gold standard; second, to ascertain the genetic property of leptin; and third, to evaluate the association between leptin concentration and PCOS. A total of 154 Tehran-resident female-female twins were studied. They included 48 pairs of monozygotic (MZ) and 29 pairs of dyzygotic (DZ) twins, aged 15-45 years. Clinical, ultrasound and biochemical findings were used to diagnose PCOS. The incidence of PCOS using biochemical and clinical features was 16.2%. The correlation coefficient between serum leptin levels of MZ twins was higher than that of the DZ twins. The serum level of leptin was similar between subjects with or without PCOS, irrespective of their zygosity. It was concluded that the incidence of PCOS is high among twins, and that leptin is likely to be genetically determined, although the effect of environmental factors cannot be denied. This study did not find any association between the diagnosis of PCOS and leptin level. However, the link between the two may lie with other entities such as eating disorders and/or obesity.

Topics: Adolescent; Adult; Diseases in Twins; Female; Humans; Incidence; Iran; Leptin; Middle Aged; Polycystic Ovary Syndrome; Twins, Dizygotic; Twins, Monozygotic

The results of recent research have confirmed the leptin control system. Leptin is produced in fatty tissue, crosses the blood-brain barrier, and signals repletion of fat stores. This in turn triggers a reduction in food intake and an increase in energy expenditure. While neuropeptide Y is known to play a central nervous mediator role, it is not certain whether leptin plays a marginal or a main role in the energy balance. Of at least equal, and possibly even greater practical/clinical importance are the results of research on the family and twins. For these reveal a tendency for weight increase and abdominal storage of fat and increased intake of calories to have a strong genetic link. The conclusions are a lowering of the expectations placed in reduction dieting, and an increase in efforts aimed at prevention.

Topics: Animals; Body Composition; Character; Disease Models, Animal; Diseases in Twins; Genetic Predisposition to Disease; Humans; Leptin; Mice; Obesity; Rats; Twin Studies as Topic

Plasma levels of leptin, the recently discovered satiety hormone, are associated with adiposity in humans.. To determine whether genetic factors or body fat distribution affect the association between leptin levels and obesity.. 23 healthy identical twin pairs (9 male pairs and 14 female pairs, 33 to 59 years of age) who were discordant for obesity (average weight difference, 18 kg).. Fasting plasma leptin levels were measured by radioimmunoassay. Distribution of abdominal fat into visceral and subcutaneous compartments was estimated by use of magnetic resonance imaging.. Plasma leptin levels were threefold higher in obese twins than in lean twins (mean +/- SD, 18.7 +/- 12.5 micrograms/L compared with 6.4 +/- 4.8 micrograms/L; P < 0.001); a similar difference was seen when the entire study group was divided according to sex. Compared with lean twins, plasma leptin levels were 3.7-fold higher in the obese twins who had visceral fat accumulation greater than the median and 2.1-fold higher in the obese twins who had visceral fat accumulation less than the median. The intrapair differences in leptin levels correlated with the corresponding differences in percentage of body fat in women (r = 0.73; P = 0.003) but not in men and correlated with differences in visceral fat area in men (r = 0.79; P = 0.019) and women (r = 0.73; P = 0.007). In multiple regression analyses that included intrapair differences in visceral fat area and total body fat, the association between differences in visceral fat area and leptin levels was significant in men (P = 0.029) but not in women.. Plasma leptin levels are increased in obese persons, independent of genetic background. Visceral fat may be of special importance in the regulation of leptin levels, but it is probably less important in women than in men.

Topics: Adipose Tissue; Adult; Body Mass Index; Diseases in Twins; Female; Humans; Leptin; Magnetic Resonance Imaging; Male; Middle Aged; Obesity; Proteins; Regression Analysis; Sex Factors; Twins, Monozygotic