leptin and Acanthosis-Nigricans

To evaluate levels of soluble receptor (sOB-R) and free leptin in women with polycystic ovarian syndrome (PCOS) and note any relationships with insulin resistance, adiposity, and androgens. Leptin is an adipokine that circulates in a free form and bound to an sOB-R. Only free leptin is biologically active.. Prospective, case-control study.. University-based reproductive endocrinology practice.. Forty women with PCOS and severe insulin resistance and 15 body mass index (BMI)-matched ovulatory controls.. Measurements of serum insulin, leptin, sOB-R at fasting and during a standard oral glucose tolerance test (OGTT), and measurements before and after treatment with rosiglitazone.. Fasting glucose, insulin, leptin, sOB-R, T, and DHEAS levels in women with PCOS and controls were measured to investigate the relationship of sOB-R and the free leptin index (FLI) to insulin, adipocity, and androgens and to investigate the effect of acute hyperinsulinemia during OGTT and the effect of improvement of insulin resistance with rosiglitazone on the leptin system. FLI was calculated by dividing leptin levels by sOB-R.. Total leptin and FLI correlated significantly with BMI in both patients with PCOS and in controls. There was a significant negative correlation between DHEAS and sOB-R in PCOS. Leptin, sOB-R, and FLI were not significantly different in the two groups, and neither sOB-R nor FLI correlated with insulin or glucose levels. The sOB-R levels increased significantly 3 hours after oral glucose ingestion, resulting in a significant decline in FLI.. [1] Adiposity rather than insulin resistance appears to be the main determinant of leptin levels and FLI. [2] Acute increase in insulin levels during OGTT is associated with an increase in levels of sOB-R. [3] DHEAS may play a role in leptin bioavailability by modulating sOB-R levels.

Topics: Acanthosis Nigricans; Adiposity; Adult; Androgens; Body Mass Index; Case-Control Studies; Comorbidity; Female; Humans; Incidence; Insulin Resistance; Leptin; Obesity; Polycystic Ovary Syndrome; Receptors, Cell Surface; Receptors, Leptin; Risk Assessment; Risk Factors; Texas

Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of "adiposopathy.". A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program.. Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group.. The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction ("adiposopathy") in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

Topics: Acanthosis Nigricans; Adiponectin; Adipose Tissue; Adolescent; Adult; Asian People; Cross-Sectional Studies; Female; Humans; Hyperandrogenism; India; Insulin Resistance; Interleukin-6; Leptin; Polycystic Ovary Syndrome; Tumor Necrosis Factor-alpha; Young Adult

Obesity-related comorbidities are present in young obese children, providing a platform for early adult cardiovascular disorders.. To compare and correlate markers of adiposity to metabolic disturbances, vascular and cardiac morphology in a European pediatric obese cohort.. We carried out an observational and transversal analysis in a cohort consisting of 121 obese children of both sexes, between the ages of 6 and 17 years. The control group consisted of 40 children with normal body mass index within the same age range. Markers of adiposity, plasma lipids and lipoproteins, homeostasis model assessment-insulin resistance, common carotid artery intima-media thickness and left ventricular diameters were analyzed.. There were statistically significant differences between the control and obese groups for the variables analyzed, all higher in the obese group, except for age, high-density lipoprotein cholesterol and adiponectin, higher in the control group. In the obese group, body mass index was directly correlated to left ventricular mass (r=0.542; p=0.001), the homeostasis model assessment-insulin resistance (r=0.378; p=<0.001) and mean common carotid artery intima-media thickness (r=0.378; p=<0.001). In that same group, insulin resistance was present in 38.1%, 12.5% had a combined dyslipidemic pattern, and eccentric hypertrophy was the most common left ventricular geometric pattern.. These results suggest that these markers may be used in clinical practice to stratify cardiovascular risk, as well as to assess the impact of weight control programs.

Topics: Acanthosis Nigricans; Adiponectin; Adiposity; Adolescent; Age Factors; Biomarkers; Body Mass Index; Cardiovascular Diseases; Carotid Intima-Media Thickness; Case-Control Studies; Child; Cross-Sectional Studies; Dyslipidemias; Female; Humans; Hypertrophy, Left Ventricular; Insulin Resistance; Leptin; Lipoproteins; Male; Pediatric Obesity; Risk Factors; Sex Factors; Waist Circumference

To investigate adipokines levels in obese children with acanthosis nigricans (AN) and to explore the relationship between AN and metabolic syndrome (MS).. A cross-sectional study was performed on 109 obese children and 47 age- and gender-matched normal controls. The obese children were divided into two groups with AN and without AN. Serum levels of adiponectin, leptin, TNF-α and retinol-binding protein 4 (RBP4) were measured using ELISA. Multiple logistic regression analysis was performed to estimate the association of clinical parameters with MS.. Waist-hip ratio, systolic blood pressure, triglyceride, fasting insulin and insulin resistance index (HOMA-IR) were significantly higher in obese children with AN than in those without AN and normal controls (P<0.05). The obese children with AN and without AN had lower adiponectin levels than normal controls (P<0.05), on the contrary, the obese children with AN had higher leptin levels than those without AN and normal controls (P<0.05). Multiple logistic regression analysis revealed that AN (OR=3.469, 95%CI: 1.518-7.929) and BMI (OR=7.108, 95%CI: 2.359-21.416) were independent risk factors for MS.. As a visible marker of insulin resistance, AN is associated with abnormal adipokines secretion. Reducing the incidence of AN and losing weight may prevent obesity associated MS.

Topics: Acanthosis Nigricans; Adiponectin; Adolescent; Child; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Logistic Models; Male; Metabolic Syndrome; Obesity

Obesity is a major public health problem that increases the risk for a broad spectrum of co-morbid conditions. Despite evidence for a strong genetic contribution to susceptibility to obesity, previous efforts to discover the relevant genes using positional cloning have failed to account for most of the apparent genetic risk variance.. Deploying a strategy combining analysis of exome sequencing data in extremely obese members of four consanguineous families with segregation analysis, we screened for causal genetic variants. Filter-based analysis and homozygosity mapping were used to identify and prioritize putative functional variants.. Two novel frameshift mutations in the leptin receptor in two of the families were identified.. These results provide proof-of-principle that whole-exome sequencing of families segregating for extreme obesity can identify causal pathogenic mutations. The methods described here can be extended to additional families segregating for extreme obesity and should enable the identification of mutations in novel genes that predispose to obesity.

Topics: Acanthosis Nigricans; Adolescent; Body Mass Index; Child; Consanguinity; Exome; Family Health; Female; Frameshift Mutation; Homozygote; Humans; Infant; Insulin; Leptin; Male; Pediatric Obesity; Pedigree; Receptors, Leptin; Sequence Analysis, DNA

Acanthosis nigricans (AN) is linked to obesity and insulin resistance. Major adipokines such as leptin, adiponectin, and resistin are known to be dysregulated in obesity and are key players in the pathogenesis of metabolic syndrome.. This study was conducted to assess serum levels of the major adipokines leptin, adiponectin, and resistin, and to study their correlations with the state of insulin resistance and other risk factors for cardiovascular disease (CVD) among AN patients.. A total of 115 adult subjects were included in the study; 52 of these had benign acquired AN, and 63 (control subjects) were without AN. Thirty-three of the control group were obese, and 30 were healthy subjects of normal weight. Body mass index (BMI), blood pressure, lipid profile, fasting blood glucose, fasting insulin, serum leptin, adiponectin, and resistin were assessed in all subjects.. We found significant differences between AN patients and obese controls in serum levels of leptin (30.02 ± 15.14 ng/ml vs. 21.07 ± 7.92 ng/ml; P = 0.002), adiponectin (5.55 ± 2.89 μg/l vs. 9.02 ± 2.33 μg/ml; P = 0.00001), and resistin (20.88 ± 3.97 ng/ml vs. 16.82 ± 4.36 ng/ml; P = 0.00003). Significant positive correlations were found between serum leptin and homeostasis model assessment (HOMA) value, insulin, glucose, BMI, cholesterol, and low-density lipoprotein. There were also significant negative correlations between adiponectin and HOMA value, insulin, BMI, cholesterol, and leptin among AN patients.. Acanthosis nigricans is a likely forerunner of the finding of metabolic syndrome. High serum leptin and resistin and low serum adiponectin may increase the risk for CVD among AN patients.

Topics: Acanthosis Nigricans; Adiponectin; Adult; Cardiovascular Diseases; Case-Control Studies; Female; Humans; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Resistin; Risk Factors

To explore the serum levels of leptin, adiponectin and sex hormone and their relationship in benign acanthosis nigricans of males.. A total of 15 males patients with benign acanthosis nigricans were recruited from January 2010 to December 2013. The serum concentrations of leptin, adiponectin and sex hormone were measured with radioimmunoassay and enzyme-linked immunoabsorbant assay (ELISA) respectively.. As compared with normal control, the values of body mass, body mass index and %Fat were much higher in benign acanthosis nigricans of males ((88 ± 6) vs (62 ± 5) kg, (31.7 ± 2.1) vs (22.2 ± 2.7) kg/m(2), 33.3% ± 2.6% vs 29.0% ± 5.8%, all P < 0.05) , leptin was much higher ((8.0 ± 1.1) vs (4.5 ± 1.5) µg/L, P < 0.01) , adiponectin was much lower ((27.7 ± 4.8) vs (38.6 ± 5.8) µg/L, P < 0.01) , estradiol and testosterone were much higher ((112 ± 28) vs (38 ± 7) pmol/L, (7.3 ± 1.9) vs (3.9 ± 2.0) nmol/L, both P < 0.01), luteinizing hormone was much lower ((128 ± 11) vs (155 ± 24) U/L, P < 0.01) . And prolactin and follicle stimulating hormone were not significantly different between two groups (both P > 0.05).. Benign acanthosis nigricans is associated with abnormal levels of lepin, adiponectin and sex hormone. And there may be some relationship between the abnormal levels of lepin and sex hormone in benign acanthosis nigricans.

Topics: Acanthosis Nigricans; Adiponectin; Body Mass Index; Estradiol; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Leptin; Luteinizing Hormone; Male; Prolactin; Skin; Testosterone

Mutations in LMNA, encoding A-type lamins, lead to multiple laminopathies, including lipodystrophies, progeroid syndromes, and cardiomyopathies. Alterations in the prelamin-A posttranslational maturation, resulting in accumulation of farnesylated isoforms, cause human progeroid syndromes. Accumulation of mutant nonfarnesylated prelamin-A leads to cardiomyopathy or progeria in mice, but no data have been provided in humans. OBJECTIVE, DESIGN, SETTING, AND PATIENTS: We searched for LMNA mutations in seven women originating from Reunion Island who were referred for a severe lipodystrophic syndrome. Clinical, molecular, genealogical, and cellular studies were performed in probands and relatives.. The seven probands showed a severe partial lipodystrophic syndrome with diabetes and/or acanthosis nigricans, liver steatosis, hypertriglyceridemia, and low serum leptin and adiponectin levels. Three probands also had severe cardiac rhythm and conduction disturbances. We identified in all probands a homozygous LMNA p.T655fsX49 mutation leading to expression of a mutated prelamin-A with 48 aberrant C-terminal amino acids, preventing its physiological posttranslational farnesylation and maturation. Genealogical and haplotype analyses were consistent with a founder mutation transmitted from a common ancestor in the 17th century. In probands' cultured fibroblasts, mutated prelamin-A was associated with typical laminopathic nuclear dysmorphies, increased oxidative stress, and premature senescence. Heterozygous relatives were asymptomatic or partially affected, in favor of a codominant transmission of the disease with incomplete penetrance in heterozygotes.. We reveal that a homozygous mutation of prelamin-A preventing its farnesylation leads to a severe lipodystrophic laminopathy in humans, which can be associated with cardiac conduction disturbances, stressing the pathogenicity of nonfarnesylated prelamin-A in human laminopathies.

Topics: Acanthosis Nigricans; Adiponectin; Adult; Arrhythmias, Cardiac; Cellular Senescence; Diabetes Mellitus; Fatty Liver; Female; Fibroblasts; Founder Effect; Humans; Hypertriglyceridemia; Lamin Type A; Leptin; Lipodystrophy; Middle Aged; Mutation; Nuclear Proteins; Oxidative Stress; Phenotype; Prenylation; Protein Precursors; Young Adult

Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipokines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children.. We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans, age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression.. There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05).. Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

Topics: Acanthosis Nigricans; Adipokines; Adiponectin; Body Weight; Brazil; Cardiovascular Diseases; Case-Control Studies; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Insulin Resistance; Leptin; Lipids; Logistic Models; Male; Metabolic Syndrome; Obesity; Overweight; Risk Factors

Topics: Acanthosis Nigricans; Humans; Leptin; Obesity

Topics: Abdominal Fat; Acanthosis Nigricans; Adolescent; Atherosclerosis; Bone Diseases, Endocrine; Child; Fatty Liver; Ghrelin; Humans; Hyperandrogenism; Hypertension; Insulin; Insulin Resistance; Leptin; Obesity; Peptide Hormones; Phenotype; Satiation; Sleep Apnea Syndromes

To clarify the clinical significance of acanthosis nigricans (AN) and the association of gene polymorphisms in the ss2- and ss3-adrenergic receptors (B2ADR and B3ADR) in Japanese obese children and adolescents.. Seventy obese subjects (56 boys, 14 girls) from 5 to 19 y of age were examined as to clinical features. Genetic analyses were performed in 83 obese subjects (61 boys, 22 girls), 2 to 17 y of age. Typing of gene polymorphisms in B2ADR and B3ADR was achieved by polymerase chain reaction (PCR) of genomic DNA and restriction fragment-length polymorphism analysis (PCR-RFLP).. The group with AN (n = 30) had higher values for percent overweight, BMI, waist circumference, fasting insulin, HOMA-R, leptin and PAI-1 than the AN-negative group (n = 40), but there were no significant differences in age, sex or percent body fat between the two groups. The prevalences of B2ADR Gly16 and B3ADR Arg64 were significantly higher in AN-positive (n = 26) than in AN-negative (n = 57) subjects. In addition, the AN frequency was significantly higher in the group with both Gly16 and Arg64 than in the group with neither of these alleles (55.6% vs 12.5%, p < 0.05).. We demonstrate that AN is a useful clinical marker for the severity of obesity associated with a high BMI, and that B2ADR Gly16 and B3ADR Arg64 are associated synergistically with AN in obese children and adolescents.

Topics: Acanthosis Nigricans; Adolescent; Adult; Asian People; Body Mass Index; Child; Child, Preschool; DNA; DNA Primers; Female; Gene Frequency; Humans; Japan; Leptin; Male; Obesity; Polymorphism, Restriction Fragment Length; Radioimmunoassay; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3; Reverse Transcriptase Polymerase Chain Reaction

Topics: Acanthosis Nigricans; Adult; Elbow; Female; Foot; Humans; Knee; Leptin; Obesity

Topics: 1-Acylglycerol-3-Phosphate O-Acyltransferase; Acanthosis Nigricans; Acyltransferases; Adipose Tissue; Adult; Diabetes Mellitus, Type 2; Fatty Liver; Female; Hirsutism; Humans; Hyperphagia; Hypertriglyceridemia; Insulin Resistance; Leptin; Lipodystrophy; Menstruation Disturbances

Alstrom syndrome is a very rare autosomal recessive inherited disorder. Only 50 cases have been reported since the syndrome was first described in 1959. This syndrome is characterized by obesity, impaired glucose tolerance with insulin resistance, retinal degeneration, neurosensory deafness, acanthosis nigricans, hepatic dysfunction, and some endocrine disorders. The index case of this report was a 12-year-old girl who became blind at the age of 6 years as the result of progressively impaired vision. At the age of 12, diabetes mellitus was diagnosed and acanthosis nigricans presented in the neck, axilla, and groin regions. Her 10-year-old brother had similar symptoms. Electroretinography and audiometry disclosed generalized pigmentary epithelial change, decreased to absent cone and rod responses, and moderate sensorineural hearing loss in both siblings. Biochemistry and oral glucose tolerance tests showed diabetes mellitus, dyslipidemia, and hepatic dysfunction in the index case. Elevations of insulin, C-peptide, and leptin concentrations were found in both siblings. Insulin resistance was also demonstrated in both siblings using the modified insulin suppression test with constant infusion of somatostatin and exogenous insulin.

Topics: Acanthosis Nigricans; Child; Deafness; Female; Humans; Insulin Resistance; Leptin; Liver Diseases; Male; Retinal Degeneration; Syndrome