Distribution of body weight, blood insulin and lipid levels in the SMXA recombinant inbred strains and the QTL analysis.

In the SMXA recombinant inbred (RI) strains, we measured body weight, blood insulin and lipid (triglyceride, total cholesterol and phospholipid) levels in each strain. In the five traits, mean values of substrains varied remarkably and showed a continuous spectrum of distribution, suggesting control by multiple genes at distinct loci for each trait. We also screened for quantitative trait loci (QTLs) involved in the five traits. Suggestive QTLs for body weight (Chromosomes 1 and 6), insulin (Chromosomes 1, 3, 10 and 17), triglyceride (Chromosomes 4 and 11) and phospholipid (Chromosome 18) levels were detected. The SMXA RI strains are unique tools for analyzing genetic factors that influence body weight, blood insulin and lipids levels.     

A genetic contribution to circulating cytokines and obesity in children

Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children enrolled in VIVA LA FAMILIA Study. Cytokine phenotypes included monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-beta1), C-reactive protein (CRP), regulated upon activation, normal T-cell expressed and secreted (RANTES) and eotaxin. Obesity-related phenotypes included body mass index (BMI), fat mass (FM), truncal FM and fasting serum insulin. Heritabilities ranged from 0.33 to 0.97. Pleiotropy was observed between cytokines and obesity traits. Positive genetic correlations were seen between CRP, leptin, MCP-1 and obesity traits, and negative genetic correlations with adiponectin, ICAM-1 and TGF-beta1. Genome-wide scan of sICAM-1 mapped to chromosome 3 (LOD=3.74) between markers D3S1580 and D3S1601, which flanks the adiponectin gene (ADIPOQ). Suggestive linkage signals were found in other chromosomal regions for other cytokines. In summary, significant heritabilities for circulating cytokines, pleiotropy between cytokines and obesity traits, and linkage for sICAM-1 on chromosome 3q substantiate a genetic contribution to circulating cytokine levels in Hispanic children.     

Relationship between adiponectin and metabolic variables in Caribbean offspring of patients with type 2 diabetes mellitus.

AIM: To examine the relationship between adiponectin and metabolic variables in the offspring of patients with type 2 diabetes mellitus. METHODS: Fasting blood samples and anthropometric indices were taken from 34 subjects, offspring of patients with type 2 diabetes, and 24 healthy control subjects without any immediate family history of diabetes. Plasma glucose and serum adiponectin, insulin, triglycerides, total cholesterol, HDL and LDL cholesterol levels were measured, and insulin resistance (IR) was calculated based on the homeostasis model assessment (HOMA) method. RESULTS: Offspring and control subjects were sex-matched, but the offspring were older and had higher body mass index and waist circumference than the control subjects (p < 0.05). The offspring had significantly higher mean fasting plasma glucose concentrations; however, their mean serum insulin, adiponectin, triglyceride, total cholesterol, HDL and LDL cholesterol and HOMA-derived IR levels did not significantly differ from those of the control subjects (p > 0.05). While the negative correlation between serum adiponectin and HDL cholesterol levels in the offspring remained statistically significant after adjusting for the effect of age, sex and BMI (r = -0.37, p < 0.05), the negative correlation between adiponectin and serum triglyceride, LDL cholesterol or IR levels became non-significant after controlling for the above variables (p > 0.05 in all cases). CONCLUSION: The correlation between adiponectin and some known biochemical risk factors for developing diabetes and cardiovascular disease in the offspring of patients with diabetes warrants further study to evaluate its potential in assessing the risk of developing these disorders.     

Adipocyte-derived hormones in heroin addicts: the influence of methadone maintenance treatment

Heroin addiction markedly affects the nutritional and metabolic status and frequently leads to malnutrition. The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects. Basal serum leptin and adiponectin levels in heroin addicts were significantly decreased (3.4+/-0.4 vs. 4.5+/-0.6 ng/ml and 18.9+/-3.3 vs. 33.9+/-3.1 ng/microl, respectively; p 0.05) while serum resistin concentrations were increased compared to healthy subjects (10.1+/-1.2 vs. 4.6+/-0.3 ng/ml; p 0.05). Moreover, positive correlation of serum leptin levels with body mass index was lost in the addicts in contrast to control group. One year of methadone maintenance treatment normalized serum leptin, but not serum adiponectin and resistin concentrations. In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction. These alterations appear to be relatively independent of nutritional status and insulin sensitivity.     

Plasma adiponectin concentration in healthy pre- and postmenopausal women: relationship with body composition, bone mineral, and metabolic variables

The aim of the current investigation was to determine the possible relationships of fasting adiponectin level with body composition, bone mineral, insulin sensitivity, leptin, and cardiorespiratory fitness parameters in 153 women. Subjects were classified as premenopausal (n = 42; 40.8 +/- 5.7 yr) if they had regular menstrual periods, early postmenopausal (n = 49; 56.7 +/- 3.6 yr) if they had been postmenopausal for more than >1 yr but <7 yr (5.5 +/- 1.3 yr), and postmenopausal (n = 62; 72.2 +/- 4.5 yr) if they had been postmenopausal for >7 yr. All women studied had a body mass index (BMI) <30 kg/m(2). Adiponectin values were higher (P < 0.05) in middle-aged (12.0 +/- 5.1 microg/ml) and older (15.3 +/- 7.3 microg/ml) postmenopausal women compared with middle-aged premenopausal women (8.4 +/- 3.2 microg/ml). Mean plasma adiponectin concentration in the total group of women (n = 153) was 12.2 +/- 6.3 microg/ml and was positively related (P < 0.05) to age, indexes of overall obesity (BMI, body fat mass), and cardiorespiratory fitness (PWC) values. In addition, a negative association (P < 0.05) between adiponectin with central obesity (waist-to-hip and waist-to-thigh ratio), fat-free mass, bone mineral (bone mineral content, total and lumbar spine bone mineral density), and leptin and insulin resistance (insulin, fasting insulin resistance index) values was observed. However, multivariate regression analysis revealed that only age, fasting insulin resistance index, and leptin were independent predictors of adiponectin concentration. In conclusion, circulating adiponectin concentrations increase with age in normal-weight middle-aged and older women. It appears that adiponectin is independently related to age, leptin, and insulin resistance values in women across the age span and menstrual status.     

Association of the + 45T > G adiponectin gene polymorphism with insulin resistance in non-diabetic Saudi women

Background

The human adiponectin gene variations are associated with obesity, insulin resistance, and diabetes. However, these associations have not been fully examined in a non-diabetic population in Saudi Arabia. We aimed to investigate the association of 45T > G single nucleotide polymorphism (SNP) in the adiponectin gene with total adiponectin levels, insulin resistance (IR), fasting blood glucose (FBG) and other markers of obesity in non-diabetic Saudi females.

Methods

One hundred non diabetic Saudi females were enrolled in this study. They were further divided according to their body mass index (BMI) into two groups. Group I, 46 non diabetic subjects with normal body weight and group II, 54 overweight and obese females. Adiponectin 45T/G polymorphism was detected by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Serum adiponectin was measured by ELISA.

Results

Obese women exhibited a higher distribution of TG/GG genotype compared with non-obese women. SNP + 45T > G genotypes were associated with higher FBG, insulin levels and HOMA–IR with lower total adiponectin levels in obese Saudi women. Otherwise the all estimated variables revealed non-significant differences among the non-obese genotypes. The observed differences in insulin resistance markers were very significant among women with a higher body weight but not among normal body weight women, thus suggesting that SNP + 45T > G effects on insulin sensitivity may depend upon body weight and body fat status.

Conclusion

SNP + 45T > G of adiponectin gene has a significant role in the development of insulin resistance in Saudi women possibly through an interaction with increase body weight and hypoadiponectinemia.     

Molecular forms of adiponectin: Comparative evaluation of their correlations with parameters of carbohydrate and lipid metabolism

Interrelationship between total, multimer (MM) and oligomer (OM) adiponectin blood concentrations with some metabolic parameters has been investigated in 49 men and 49 women (mean age of 57.3 ± 10.1 years). We have found negative correlations between total blood adiponectin and its MM form content with body mass index, waist circumference, the insulin resistance index HOMA, with blood concentrations of insulin, glucose, free fatty acids, triglycerides and also positive correlations with high density lipoprotein cholesterol content. There was a poor correlation between OM adiponectin concentration with any parameter studied. According to the regression analysis, concentration of total adiponectin but not its MM form was an independent determinant of the HOMA index in women and free fatty acid concentration in men. In the group of men with the low level of adiponectin its MM form but not total adiponectin reversely correlated with the HOMA index and was its independent determinant. Thus, correlation between blood adiponectin concentration and metabolic parameters is associated with its MM rather than OM form. Study of the role of adiponectin in development of metabolic disorders may be limited to determination of total blood adiponectin concentration except a group of male patients characterized by a low level of this adipokine. In these patients concentrations of the MM form should be determined.     

Serum adiponectin levels are associated with hepatitis B viral load in overweight to obese hepatitis B virus carriers

Objective:

This study aimed to investigate the association between serum adiponectin and chronic hepatitis B virus (HBV) infection.

Design and Methods:

We conducted a campus‐based cross‐sectional study in Northern Taiwan, an HBV‐endemic country. A total of 506 participants, including 147 chronic HBV‐infected individuals and 359 healthy controls, were assessed for anthropometric indices, serum adiponectin levels, serum HBV viral load and markers, serum alanine aminotransferase levels and metabolic factors.

Results:

Older age, male gender, higher alanine aminotransferase, higher body mass index, greater waist circumference, lower fasting glucose, higher triglycerides, and higher adiponectin were associated with chronic HBV infection in univariate analyses. In multivariate analysis, the presence of chronic HBV infection was positively associated with serum adiponectin levels (P < 0.0001) and high adiponectin levels over the 75th percentile (odds ratio, 4.25; 95% confidence interval, 2.36‐7.66; P < 0.0001) after adjusting for age, gender, body mass index, and insulin resistance index. Furthermore, serum adiponectin levels were positively associated with HBV viral load in overweight to obese HBV‐infected subjects (P = 0.018).

Conclusion:

Although chronic HBV‐infected individuals were heavier than healthy controls, they had significantly higher serum adiponectin levels than healthy counterparts. Additionally, adiponectin levels were positively associated with HBV viral load in overweight to obese HBV‐infected subjects. Future research should focus on elucidating adiponectin pathways, which may contribute to the development of adjuvant treatments for chronic HBV infection.     

Dehydroepiandrosterone prevents age-associated alterations, increasing insulin sensitivity

The age decline in DHEA levels has been associated with the appearance of age-related disorders such as obesity and insulin resistance. The aim of this study was to analyse the effect of chronic administration (13 weeks) of DHEA (5 g/kg diet) to old female rats fed on a high-fat diet on body weight and adiposity, and concretely on the expression of the adipokines related to obesity and insulin resistance, such as leptin, adiponectin and resistin. DHEA treatment induced a decrease in body weight, adipose tissue mass and serum insulin, adiponectin and leptin levels. Adiponectin mRNA expression in visceral fat depots decreased with aging, but this reduction was attenuated by DHEA treatment. DHEA treatment also stimulated resistin gene expression in the ovaric and renal adipose depots, which is associated with an increase in its circulating levels. In conclusion, DHEA treatment decreases body weight and adiposity in old female rats fed a high-fat diet, leading to an improvement of the HOMA index for insulin sensitivity, with decreasing circulating insulin levels, and preventing the age-associated decline of visceral-adipose adiponectin expression.     

Adiponectin and negative mood in healthy premenopausal and postmenopausal women

Negative mood and stress are associated with cardiovascular and metabolic disease. There are likely many physiological mechanisms underlying the poor health outcomes. The relationship of psychological states (negative mood, life stress, and stress-responsive hormones) and adiponectin, an adipokine that promotes insulin sensitivity, was investigated in two separate studies. The two groups of participants included 52 healthy, premenopausal women, and 63 postmenopausal women with a range of stress levels. The relationship between adiponectin and psychological state (perceived stress and negative mood) was examined cross-sectionally in both groups of participants, but also prospectively (1 year later) in the group of postmenopausal women.In premenopausal women, negative mood and nocturnal urinary epinephrine were significantly related to adiponectin, independent of BMI. In postmenopausal women, negative mood was not associated with adiponectin cross-sectionally, but negative mood was a significant predictor for lower levels of adiponectin 1 year later, independent of initial adiponectin concentrations and changes in body mass index. Lastly, having a depressive disorder was related to lower adiponectin. As adiponectin levels are associated with insulin resistance, obesity, and diabetes mellitus, these findings suggest there may be an adiponectin-mediated pathway explaining in part how negative mood affects metabolic health. Mechanistic studies are needed to explore this potential relationship further.     

Relatively high levels of serum adiponectin in obese women, a potential indicator of anti-inflammatory dysfunction: relation to sex hormone-binding globulin

It is unclear whether serum adiponectin concentrations diminish linearly with increasing adiposity and, if not, which factors codetermine this association. These issues were investigated cross-sectionally in 1188 men and women, representative of middle-aged and elderly Turkish adults. Serum total adiponectin was assayed by ELISA. Serum adiponectin values in men, though declining significantly in transition from the bottom to the mid tertile of body mass index (BMI) and waist circumference (WC), were similar in the two respective upper tertiles. In women, serum adiponectin concentrations were not significantly different in any tertile of these indices, were significantly correlated with BMI or WC within the low tertiles and not within the two higher tertiles. In a linear regression analysis for WC (or BMI) in a subset of the sample in which serum sex hormone-binding globulin (SHBG) was available and which additionally comprised adiponectin, fasting insulin and other confounders, only insulin and, in women SHBG, were significantly associated, but not adiponectin. In linear regression analyses for covariates of adiponectin in two models comprising 12 variables, insulin and SHBG concentrations were significantly associated in both genders though not BMI. Whereas in men HDL-cholesterol and CRP were covariates of adiponectin (both p<0.01), SHBG and apolipoprotein B positively associated in women (p<0.001), independent of BMI and fasting insulin levels. CONCLUSIONS: Relationship between excess adiposity and adiponectin levels is inconsistent in Turkish adults. Independently from obesity and hyperinsulinemia, serum adiponectin discloses significant relationship with inflammatory markers and HDL only in men, not in women in whom it is influenced by SHBG, with consequent attenuation of its anti-inflammatory activities.     

Chemerin and adiponectin contribute reciprocally to metabolic syndrome

Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15 ± 5.08 kg/m(2). Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00-33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS.     

Increased insulin sensitivity in patients with anorexia nervosa: the role of adipocytokines

Anorexia nervosa (AN) is characterized by self-induced starvation leading to severe weight and fat loss. In the present study, we measured fasting plasma levels of adiponectin, leptin, resistin, insulin and glucose in 10 women with a restrictive type of AN and in 12 healthy women (C). Insulin sensitivity was determined according to homeostasis model assessment of insulin resistance (HOMA-R). Plasma resistin, leptin and insulin levels were significantly decreased, whereas plasma adiponectin levels were significantly increased in patients with AN compared to the C. HOMA-R was significantly decreased in patients with AN compared to the C group. Plasma adiponectin and leptin concentrations negatively and positively correlated with the body mass index and percentage body fat in both groups. Plasma adiponectin levels were negatively related to plasma insulin levels in the AN group only. In conclusion, we demonstrated that AN is associated with significantly decreased plasma leptin and resistin levels, markedly increased plasma adiponectin levels and increased insulin sensitivity. Plasma leptin and adiponectin levels were related to the body size and adiposity. Hyperadiponectinemia could play a role in increased insulin sensitivity of patients with AN. Neither body size and adiposity nor insulin sensitivity are the major determinants of plasma resistin levels in AN.     

Decreased total serum adiponectin and its isoforms in women with acute ischemic stroke

OBJECTIVE: An association between cerebral infarct risk factors and serum adiponectin levels (both total and separate isoforms) has previously been identified. The aim of this study was to assess circulating levels of all forms of adiponectin in the course of an ischemic stroke. Material and methods: Adiponectin and its isoforms (HMW, MMW and LMW) were measured in serum samples taken from 38 women in the first 24 hours of cerebral infarct and 38 controls matched for gender, body mass index (BMI) and age. In addition, biochemical parameters (glucose, insulin, lipid profile) and clinical data (blood pressure, weight, and height) were evaluated. Results: A significant reduction in serum levels of adiponectin and all examined fractions of this adipokine was observed in women suffering from acute ischemic stroke, compared with the matched controls. Conclusions: Differences in the serum adiponectin array between stroke subjects and controls were identified and further studies are required to investigate the clinical implications of this finding.     

Detection of loci for allergic asthma using SMXA recombinant inbred strains of mice

Asthma is regarded as a multifactorial inflammatory disorder arising as a result of inappropriate immune responses in genetically susceptible individuals to common environmental antigens. However, the precise molecular basis is unknown. To identify genes for susceptibility to three asthma-related traits, airway hyperresponsiveness (AHR), eosinophil infiltration, and allergen-specific serum IgE levels, we conducted a genetic analysis using SMXA recombinant inbred (RI) strains of mice. Quantitative trait locus analysis detected a significant locus for AHR on chromosome 17. For eosinophil infiltration, significant loci were detected on chromosomes 9 and 16. Although we could not detect any significant loci for allergen-specific serum IgE, analysis of consomic strains showed that chromosomes 17 and 19 carried genes that affected this trait. We detected genetic susceptibility loci that separately regulated the three asthma-related phenotypes. Our results suggested that different genetic mechanisms regulate these asthma-related phenotypes. Genetic analyses using murine RI and consomic strains enhance understanding of the molecular mechanisms of asthma in human.     

Genetic Models in Applied Physiology. HXB/BXH rat recombinant inbred strain platform: a newly enhanced tool for cardiovascular, behavioral, and developmental genetics and genomics.

This review deals with the largest set of rat recombinant inbred (RI) strains and summarizes past and recent accomplishments with this platform for genetic mapping and analyses of divergent and complex traits. This strain, derived by crossing the spontaneously hypertensive rat, SHR/Ola, with a Brown Norway congenic, BN-Lx, carrying polydactyly-luxate syndrome, is referred to as HXB/BXH. The RI strain set has been used for linkage and association studies to identify quantitative trait loci for numerous cardiovascular phenotypes, including arterial pressure, stress-elicited heart rate, and pressor response, and metabolic traits, including insulin resistance, dyslipidemia and glucose handling, and left ventricular hypertrophy. The strain's utility has been enhanced with development of a new framework marker-based map and strain distribution patterns of polymorphic markers. Quantitative trait loci for behavioral traits mapped include loci for startle motor response and habituation, anxiety and locomotion traits associated with elevated plus maze, and conditioned taste aversion. The polydactyly-luxate syndrome Lx mutation has allowed the study of alleles important to limb development and malformation phenotypes as well as teratogens. The RI strains have guided development of numerous congenic strains to test locus assignments and to study the effect of genetic background. Although these strains were originally developed to aid in studies of rat genetic hypertension and morphogenetic abnormalities, this rodent platform has been shown to be equally powerful for a wide spectrum of traits and endophenotypes. These strains provide a ready and available vehicle for many physiological and pharmacological studies.     

Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

Background

Adiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IR_AR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.

Methods

In this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.

Results

The AR index was formulated as 1+log₁₀(R₀)-log₁₀(A₀). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IR_AR index was formulated as log₁₀(I₀G₀)+log₁₀(I₀G₀)log₁₀(R₀/A₀). The normal reference range of the IR_AR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IR_AR index for insulin resistance assessment were between 3.538 and 3.955.

Conclusions

The novel AR and IR_AR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.     

Adiponectin is associated with bone mineral density in perimenopausal women.

The aim of the current investigation was to investigate any potential effect of fasting plasma adiponectin concentration on bone tissue, and to find possible relationships of fasting plasma adiponectin level with different body composition, insulin sensitivity and physical performance parameters in a group of healthy perimenopausal women. Twenty-one premenopausal and 17 early postmenopausal women participated in this study. The women were matched for body mass index (BMI) and level of mean daily energy expenditure. Women had similar adiponectin (8.4 +/- 3.9 vs. 9.9 +/- 5.4 microg/ml) and leptin values (12.0 +/- 7.7 vs. 14.0 +/- 8.2 ng/ml) before and after menopause. Significant relationships were observed between plasma adiponectin and bone mineral content, total bone mineral density (BMD) and lumbar spine BMD values (r > - 0.36; p < 0.05). Furthermore, adiponectin had a significant negative association with total BMD (beta = - 1.228; p = 0.004) and lumbar spine BMD (beta = - 0.312; p = 0.005) independent of the influence that other measured body compositional, hormonal or physical performance factors may exert on BMD. Adiponectin was also significantly related to waist-to-hip ratio (WHR) (beta = - 2.300; p = 0.002) and fasting insulin resistance index (FIRI) (beta = - 0.006; p = 0.007) in separate regression models. No relationship was observed between leptin and measured bone, physical performance and insulin resistance values. Leptin significantly correlated to BMI (beta = 0.018; p = 0.034), lean body mass (beta = 0.025; p = 0.024) and fat mass (beta = 0.019; p = 0.001) in separate regression models. In conclusion, the results of present study show that circulating adiponectin appears to exert an independent effect on BMD in perimenopausal women and may represent a link between adipose tissue and bone mineral density.     

Downregulation of ADIPOQ and PPARγ2 Gene Expression in Subcutaneous Adipose Tissue of Obese Adolescents With Hepatic Steatosis

Hepatic steatosis is associated with hypoadiponectinemia. The mechanism(s) resulting in lower serum adiponectin levels in obese adolescents with fatty liver is unknown. In two groups of equally obese adolescents, but discordant for hepatic fat content, we measured adiponectin, leptin, peroxisome proliferator–activated receptor γ 2 (PPARγ2) and tumor necrosis factor‐α (TNFα) gene expression in the abdominal subcutaneous adipose tissue (SAT). Twenty six adolescents with similar degrees of obesity underwent a subcutaneous periumbilical adipose tissue biopsy, in addition to metabolic (oral glucose tolerance test, and hyperinsulinemic—euglycemic clamp), and imaging studies (magnetic resonance imaging (MRI), DEXA). Using quantitative real‐time‐PCR; adiponectin, PPARγ2, TNFα, and leptin mRNA were measured. Based on a hepatic fat content (hepatic fat fraction, HFF) >5.5%, measured by fast MRI, the subjects were divided into low and high HFF group. In addition to the hypoadiponectinemia in the high HFF group, we found that the expression of adiponectin as well as PPARγ2 in the SAT was significantly decreased in this group. No differences were noted for TNFα and leptin plasma or mRNA levels between the groups. An inverse relationship was observed between adiponectin or PPARγ2 expression and hepatic fat content, whereas, adiponectin expression was positively related to PPARγ2 expression. Independent of overall obesity, a reduced expression of adiponectin and PPARγ2 in the abdominal SAT is associated with high liver fat content, as well as with insulin resistance in obese adolescents.