Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population.

Leptin plays an important role in the regulation of body weight and is known to circulate in both free and bound forms. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. Clinical studies have shown that soluble leptin receptor (sOB-R) levels are lower in obese individuals. In the present study, we measured the serum sOB-R level in 419 healthy Japanese subjects (198 men and 221 women, aged 30 to 65 years, body mass index [BMI] 21.7 +/- 2.6 [SD] kg/m2) and in 150 type 2 diabetic patients (96 men and 54 women, BMI 24.3 +/- 3.8 kg/m2). We investigated the relationships between serum sOB-R level and BMI, blood pressure, homeostasis model assessment-insulin resistance index (HOMA-IR), serum leptin and adiponectin levels, lipid profile, and leptin receptor (LEPR) gene Lys109Arg and Gln223Arg polymorphisms. Serum leptin and sOB-R levels were measured by radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), respectively. The serum sOB-R level in men was significantly higher than that in women. The serum sOB-R level was negatively correlated with BMI, fasting insulin, HOMA-IR, and serum leptin level and positively correlated with high-density lipoprotein (HDL)-cholesterol and serum adiponectin levels. The correlations between serum sOB-R level and fasting insulin, HOMA-IR, serum leptin, adiponectin, and HDL-cholesterol levels were significant even after adjustment for age, sex, and BMI in healthy subjects. There was no association between serum sOB-R level and the LEPR polymorphisms examined. These findings suggest that the serum sOB-R level is negatively correlated with HOMA-IR and serum leptin level and positively correlated with HDL-cholesterol level and serum adiponectin level, independent of age, sex, and BMI, in the Japanese population.

Effects of leptin receptor gene 3'-untranslated region polymorphism on metabolic profiles in young Japanese men.

We investigated the effects of leptin receptor gene 3'-untranslated region (3'-UTR) polymorphism on clinical and metabolic parameters in 221 young Japanese men aged 21 to 28 years. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify a pentanucleotide (CTTTA) insertion in 3'-UTR of the leptin receptor gene. Body mass index, blood pressure, plasma glucose, insulin, leptin, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, free fatty acids, uric acid, apolipoprotein A-I (apoA-I), and cholesteryl-ester transfer protein levels were measured. There was only 1 homozygote and 38 heterozygotes for the 3'-UTR insertion allele among the 221 subjects. The insertion allele frequency was 0.090. Plasma HDL-cholesterol and apoA-I levels were significantly lower (p = 0.015 and p = 0.032 by Mann-Whitney U test, respectively) in homozygous or heterozygous carriers of the insertion allele than in subjects homozygous for the normal allele. There were no differences in other parameters measured. Furthermore, when the subjects were divided into three groups according to HDL-cholesterol level, the percentage of insertion allele-positive subjects was significantly lower in the highest HDL-cholesterol group (chi(2) = 8.42, p = 0.015). These findings suggest that serum HDL-cholesterol and apoA-I levels are influenced by the leptin receptor gene 3'-UTR polymorphism in young Japanese men.

Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two-year follow-up study in Japanese population.

It has been reported that the serum adiponectin level was negatively correlated with body mass index (BMI), insulin resistance index, and triglycerides and was positively correlated with high-density lipoprotein cholesterol in several cross-sectional studies. However, the causal relationship has not been elucidated. We investigated whether the baseline adiponectin level could predict subsequent changes in insulin resistance, lipid profile, or body weight in a 2-yr longitudinal study. This study included 590 male Japanese subjects, aged 30-65 yr, who received annual health checkups in both 2000 and 2002. Blood pressure, heart rate, and anthropometric and metabolic parameters, including serum insulin and adiponectin levels, were determined. The insulin resistance index was calculated based on homeostasis model assessment. Baseline adiponectin level was not correlated with the subsequent change in lipid profile or BMI in 2 yr after adjustment for each baseline value. However, the baseline adiponectin level was negatively correlated with subsequent changes in insulin and insulin resistance index based on homeostasis model assessment, even after adjustment for change in BMI (r = -0.162 and r = -0.140, respectively). These findings suggest that the serum adiponectin concentration predicts subsequent changes in insulin resistance, but not in lipid profile or body weight.

PPAR(gamma)2 gene Pro12Ala polymorphism may influence serum level of an adipocyte-derived protein, adiponectin, in the Japanese population.

Adiponectin is an adipocyte-derived protein, which possesses an anti-atherosclerotic action and improves insulin sensitivity. Peroxisome proliferator-activated receptor gamma (PPAR(gamma)) regulates the transcription of many adipocyte-specific genes. A Pro12Ala polymorphism has been detected in the PPAR(gamma)2 gene, and this substitution has been reported to reduce transactivation activity in vitro. We hypothesized that individuals possessing this Ala12 allele may have a lower serum adiponectin level, because of the observation that PPAR(gamma) agonists increase the plasma adiponectin level in humans. To test this hypothesis, we investigated the effects of the PPAR(gamma)2 Pro12Ala polymorphism on anthropometric and metabolic parameters, including serum adiponectin level, in 478 Japanese men and 117 women aged 30 to 65 years. There were no homozygous subjects for the Ala12 allele of the PPAR(gamma)2 gene in this study. Plasma adiponectin levels were significantly lower in subjects with the Ala12 allele in the Japanese population of both sexes, although body mass index (BMI), plasma glucose, serum lipids, and insulin resistance index were not significantly different between subjects with and without this polymorphism. It is suggested that the Pro12Ala polymorphism of the PPAR(gamma)2 gene may reduce serum adiponectin level in the Japanese population.

Correlation of the adipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein-cholesterol, independent of body mass index, in the Japanese population.

Adiponectin, which is secreted specifically by adipose tissue, has been shown to act as an anti-atherosclerotic protein by direct effects on endothelial cells. Clinical studies have shown that adiponectin levels are lower in individuals with obesity, diabetes and coronary artery disease. The present study investigated relationships between serum adiponectin levels and body mass index (BMI), blood pressure, insulin resistance index, lipid profile, uric acid and high-sensitivity C-reactive protein levels in a large number of Japanese subjects not taking any medication for metabolic disease and without severe illness (705 men and 262 women; age 30-65 years; BMI 22.5+/-2.9 kg/m(2)). The serum adiponectin concentration was measured by ELISA, without a protein-denaturing step. The insulin resistance index was assessed by homoeostasis model assessment (HOMA-IR). The serum concentration of adiponectin in women (13.5+/-7.9 microg/ml) was significantly higher than that in men (7.2+/-4.6 microg/ml). The serum adiponectin level was negatively correlated with BMI, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, insulin, HOMA-IR, total cholesterol, triacylglycerols, low-density lipoprotein (LDL)-cholesterol and uric acid, and positively correlated with high-density lipoprotein (HDL)-cholesterol. The correlations between serum adiponectin level and insulin, HOMA-IR, triacylglycerols, HDL-cholesterol, LDL-cholesterol and uric acid were significant even after adjustment for age, sex and BMI. Stepwise multiple regression analysis revealed that HDL-cholesterol, sex, BMI and HOMA-IR were independently correlated with the serum adiponectin level (R(2)=0.377). These findings suggest that the serum adiponectin level is negatively correlated with HOMA-IR and positively correlated with HDL-cholesterol, independent of age, sex and BMI, in the Japanese population.