The objective of the study was to characterize ethnic differences in lipid levels and low-density lipoprotein (LDL) particle size and subclasses in black and white South African women and to explore the associations with insulin sensitivity (S(I)), body composition, and lifestyle factors. Fasting serum lipids and LDL size and subclasses, body composition (dual-energy x-ray absorptiometry), and S(I) (frequently sampled intravenous glucose tolerance test) were measured in normal-weight (body mass index <25 kg/m(2)) black (n = 15) and white (n = 15), and obese (body mass index >30 kg/m(2)) black (n = 13) and white (n = 13) women. Normal-weight and obese black women had lower triglycerides (0.59 +/- 0.09 and 0.77 +/- 0.10 vs 0.89 +/- 0.09 and 0.93 +/- 0.10 mmol/L, P < .05) and high-density lipoprotein cholesterol (1.2 +/- 0.1 and 1.1 +/- 0.1 vs 1.7 +/- 0.1 and 1.6 +/- 0.3 mmol/L, P < .01) than white women. The LDL particle size was not different, but obese black women had more LDL subclass IV (17.3% +/- 1.0% vs 12.5% +/- 1.0%, P < .01). In white women, triglycerides and LDL particle size correlated with S(I) (P < .01), whereas cholesterol levels correlated with body fat (P < .05). Low socioeconomic status, low dietary protein intake, and injectable contraceptive use were the major determinants of unfavorable lipid profiles in black women. Black women had lower triglyceride and high-density lipoprotein cholesterol levels and more small dense LDL particles than white women. The major determinants of serum lipids in black women were socioeconomic status and lifestyle factors, whereas in white women, S(I) and body composition most closely correlated with serum lipids.

Excessive energy intake greatly contributes to the development of nonalcoholic fatty liver disease (NAFLD) in modern society. To better understand the comprehensive mechanisms of NAFLD development, we investigated the metabolic alterations of rats with NAFLD induced by high-fat diet (HFD). Male Wistar rats were fed a HFD or standard chow for control. After 16 weeks, rat serum was collected for biochemical measurement. The rats' livers were resected and subjected to histology inspection and gene expression analysis with complementary DNA microarray and metabolic analysis with gas chromatography-mass spectroscopy. In HFD rats, the serum cholesterol, triglycerides, glucose, and insulin contents were increased; and the total cholesterol and triglycerides in the livers were also significantly increased. Complementary DNA microarray analysis revealed that 130 genes were regulated by HFD. Together with real-time reverse transcriptase polymerase chain reaction, lipid metabolism regulatory members like sterol regulatory element binding factor 1 and stearoyl-coenzyme A desaturase 1 had up-regulation, whereas others like peroxisome proliferator-activated receptor, carnitine palmitoyltransferase 1, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase had repressed expression, in HFD rat livers. Metabolomic analysis showed that tetradecanoic acid, hexadecanoic acid, and oleic acid had elevation and arachidonic acid and eicosapentaenoic acid had decreased content in HFD rat livers. Amino acids including glycine, alanine, aspartic acid, glutamic acid, and proline contents were decreased. The integrative results from transcriptomic and metabolomic studies revealed that, in HFD rat livers, fatty acid utilization through beta-oxidation was inhibited and lipogenesis was enhanced. These observations facilitated our understanding of the pathways involved in the development of NAFLD induced by HFD.

The effects of the prolonged elevation of nonesterified fatty acid (NEFA) levels on insulin secretion have been controversial and thought to be sex-specific. To investigate the association between a westernized lifestyle and the effects of NEFA on insulin secretion in Japanese men, we examined 67 nondiabetic Japanese-American men and 220 nondiabetic native Japanese men who underwent a 75-g oral glucose tolerance test (OGTT). Most Japanese Americans we surveyed are genetically identical to Japanese living in Japan, but their lifestyle is more westernized. Sets of multiple regression analyses were performed to evaluate the relationship between the sum of the immunoreactive insulin (IRI) levels during the OGTT ((Sigma)IRI) and clinical parameters. Japanese Americans had higher levels of fasting IRI, (Sigma)IRI, and a higher insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]) than native Japanese, whereas there were no significant differences in fasting NEFA and triglyceride levels. A multiple regression analysis adjusted for age, fasting triglycerides, and body mass index (BMI) demonstrated that the fasting NEFA level was an independent determinant of the (Sigma)IRI only in Japanese-American men ( P = .001), but not in native Japanese men ( P = .054). Even when HOMA-IR was included in models instead of BMI, the NEFA level was a significant variable of (Sigma)IRI only in Japanese Americans ( P < .001), and not in native Japanese ( P = .098). In addition, a multiple regression analysis adjusted for age, fasting triglycerides, and BMI demonstrated that the fasting NEFA level was the only independent determinant of (Sigma)C-peptide in Japanese-American men ( P = .041). In conclusion, NEFA seems to be associated with insulin secretion independent of obesity or HOMA-IR. A westernized lifestyle may increase the effects of serum fasting NEFA levels on total insulin secretion after a glucose load in Japanese men.

Insulin resistance constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications. Retinol binding protein 4 (RBP4) is a newly discovered adipocyte product that modulates glucose metabolism and consequently induces insulin resistance. We investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents. A total of 87 nonobese (60 males and 27 females) and 85 obese (62 males and 23 females) apparently healthy adolescents, 12 to 18 years old, were included in this study. A questionnaire was used to obtain participant medical history and lifestyle information, such as smoking and alcohol ingestion habits. Subjects' anthropometric measurements were taken to calculate for body mass index and waist-to-hip ratio. Serum RBP4 levels were measured by an enzyme immunoassay kit. High-sensitivity C-reactive protein, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and fasting insulin were measured. Low-density lipoprotein cholesterol level and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Males had significantly higher RBP4 levels than females. Serum RBP4 levels were significantly higher in the obese group compared with the nonobese group. In all subjects, RBP4 was positively correlated with adiposity index (body mass index, waist circumference, waist-to-hip ratio), systolic and diastolic blood pressures, glucose tolerance index (fasting glucose, insulin, HOMA-IR), lipid profile (total cholesterol, triglycerides), and inflammatory indices (high-sensitivity C-reactive protein, white blood cell count). In multiple linear regression analysis, RBP4 was independently associated with age, HOMA-IR, and triglyceride levels in the nonobese group and with sex and triglyceride levels in the obese group. These results suggest that serum RBP4 might have clinical implications for lipid metabolism and insulin action in adolescents.

The aim of the study was to assess the relation of adiponectin levels with the metabolic syndrome in Asian Indians, a high-risk group for diabetes and premature coronary artery disease. The study was conducted on 100 (50 men and 50 women) type 2 diabetic subjects and 100 age and sex matched subjects with normal glucose tolerance selected from the Chennai Urban Rural Epidemiology Study, an ongoing population study in Chennai in southern India. Metabolic syndrome was defined using modified Adult Treatment Panel III (ATPIII) guidelines. Adiponectin values were significantly lower in diabetic subjects (men: 5.2 vs 8.3 microg/mL, P=.00l; women: 7.6 vs 11.1 microg/mL, P<.00l) and those with the metabolic syndrome (men: 5.0 vs 6.8 microg/mL, P=.01; women: 6.5 vs 9.9 microg/mL, P=.001) compared with those without. Linear regression analysis revealed adiponectin to be associated with body mass index (P<.05), waist circumference (P<.01), fasting plasma glucose (P=.001), glycated hemoglobin (P<.001), triglycerides (P<.00l), high-density lipoprotein (HDL) cholesterol (P<.001), cholesterol/HDL ratio (P<.00l), and insulin resistance measured by homeostasis assessment model (P<.00l). Factor analysis identified 2 factors: factor 1, negatively loaded with adiponectin and HDL cholesterol and positively loaded with triglycerides, waist circumference, and insulin resistance measured by homeostasis assessment model; and factor 2, with a positive loading of waist circumference and systolic and diastolic blood pressure. Logistic regression analysis revealed adiponectin to be negatively associated with metabolic syndrome (odds ratio [OR], 0.365; P<.001) even after adjusting for age (OR, 0.344; P<.00l), sex (OR, 0.293; P<.001), and body mass index (OR, 0.292; P<.00l). Lower adiponectin levels are associated with the metabolic syndrome per se and several of its components, particularly, diabetes, insulin resistance, and dyslipidemia in this urban south Indian population.

Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndrome (PCOS) through the dysregulated production of various adipokines. Polycystic ovary syndrome has also been described as a low-grade inflammation state characterized by elevated levels of C-reactive protein (CRP). Furthermore, CRP is a strong independent predictor of the metabolic syndrome and cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been proposed as a potential atherogenic index in obese type 2 diabetic patients. The aim of this study was to evaluate the potential role of the A/L ratio in the metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with PCOS (38 normal-weight and 36 overweight-obese women). The A/L ratio was negatively correlated with BMI (r = -0.79 P < .001), homeostasis model assessment (r = -0.642, P < .001), triglycerides (r = -0.67, P < .001), and total cholesterol (r = -0.38, P < .01), and positively correlated with high-density lipoprotein cholesterol (r = 0.38, P < .01) and sex hormone-binding globulin (r = 0.39, P = .001). After controlling for BMI, the A/L ratio was independently associated with insulin resistance indexes and triglycerides. Furthermore, the A/L ratio was negatively correlated with CRP (r = -0.746, P < .0001). Multiple regression analysis revealed that BMI and the A/L ratio were the only independent significant determinants of CRP (beta = .436, P = .003 and beta = -.398, P = .007, respectively). Studying normal-weight and overweight-obese women separately, we found an independent association between the A/L ratio and CRP in both groups (beta = -.460, P = .009 in normal-weight women and beta = -.570, P = .001 in overweight-obese women). In conclusion, the A/L ratio may serve as a biomarker of both insulin resistance and low-grade inflammation, providing the link between these cardiovascular risk factors in women with PCOS.

This systematic review and meta-analysis of randomized controlled trials (RCTs) was performed to summarize the effect of alpha-lipoic acid (ALA) supplementation on glycemic control and lipid profiles among patients with metabolic diseases.

We previously demonstrated the role of a phospholipid transfer protein (PLTP) gene variation (rs2294213) in determining levels of high-density lipoprotein cholesterol (HDL-C) in hypoalphalipoproteinemia (HypoA). We have now explored the role of PLTP in hyperalphalipoproteinemia (HyperA). The human PLTP gene was screened for sequence anomalies by DNA melting in 107 subjects with HyperA. The association with plasma lipoprotein levels was evaluated. We detected 7 sequence variations: 1 previously reported variation (rs2294213) and 5 novel mutations including 1 missense mutation (L106F). The PLTP activity was unchanged in the p.L106F mutation. The frequency of the rs2294213 minor allele was markedly increased in the HyperA group (7.0%) in comparison with a control group (4.3%) and the hypoalphalipoproteinemia group (2.2%). Moreover, rs2294213 was strongly associated with HDL-C levels. Linear regression models predict that possession of the rs2294213 minor allele increases HDL-C independent of triglycerides. These findings extend the association of rs2294213 with HDL-C levels into the extremes of the HDL distribution.

Recent findings suggest that ghrelin may have a beneficial effect on vasculature. In the present study, we examined the associations between plasma ghrelin concentration and metabolic parameters in children and adolescents. We measured fasting plasma ghrelin concentrations in 50 Korean children and adolescents (28 boys and 22 girls, mean +/- SD age 12.6 +/- 2.7 years, body mass index 22.7 +/- 5.1 kg/m 2 ), and analyzed the associations between fasting plasma ghrelin level and anthropometric measurements, metabolic parameters, leptin concentration, and fasting insulin level. We found that fasting plasma ghrelin concentration was negatively correlated with height, weight, body mass index, percent body fat, waist circumference, and hip circumference in both boys and girls. Fasting plasma ghrelin levels were significantly negatively correlated with triglycerides and fasting insulin levels and positively correlated with high-density lipoprotein cholesterol in boys, but not in girls. Our results thus demonstrate that higher plasma ghrelin levels have beneficial effects on metabolic parameters in boys and that the relationships between fasting plasma ghrelin levels and metabolic parameters differed according to sex.

Fructose over-consumption contributes to the development of liver steatosis in part by stimulating ChREBPα-driven de novo lipogenesis. However, the mechanisms by which fructose activates ChREBP pathway remain largely undefined. Here we performed affinity purification of ChREBPα followed by mass spectrometry and identified DDB1 as a novel interaction protein of ChREBPα in the presence of fructose. Depletion and overexpression of Ddb1 showed opposite effects on the ChREBPα stability in hepatocytes. We next tested the impact of hepatic Ddb1 deficiency on the fructose-induced ChREBP pathway. After 3-week high-fructose diet feeding, both Ddb1 liver-specific knockout and AAV-TBG-Cre-injected Ddb1flox/flox mice showed significantly reduced ChREBPα, lipogenic enzymes, as well as triglycerides in the liver. Mechanistically, DDB1 stabilizes ChREBPα through CRY1, a known ubiquitination target of DDB1 E3 ligase. Finally, overexpression of a degradation-resistant CRY1 mutant (CRY1-585KA) reduces ChREBPα and its target genes in the mouse liver following high-fructose diet feeding. Our data revealed DDB1 as an intracellular sensor of fructose intake to promote hepatic de novo lipogenesis and liver steatosis by stabilizing ChREBPα in a CRY1-dependent manner.

Obesity is associated with low-grade chronic inflammation characterized by inflamed adipose tissue with increased infiltration of macrophages. The aim of this study was to investigate the correlations between the serum concentration of allograft inflammatory factor-1 (AIF-1), which is a marker of activated macrophages, and metabolic parameters. The serum AIF-1 concentrations were measured in 303 healthy subjects (163 men and 140 women). We then evaluated the relationships between the serum AIF-1 concentrations and metabolic parameters, including fasting plasma glucose levels, serum lipid concentration, uric acid concentration, and waist circumference. The serum AIF-1 concentrations positively correlated with levels of fasting plasma glucose (r = 0.159, P =.0056), hemoglobin A(1c) (r = 0.169, P = .0032), triglycerides (r = 0.137, P = .0172), and uric acid (r = 0.146, P = .0108) and with waist circumference (r = 0.221, P = .0001) and body mass index (r = 0.185, P = .0012), whereas the serum AIF-1 concentrations inversely correlated with high-density lipoprotein cholesterol level (r = -0.178, P = .0019). Stepwise multiple regression analysis demonstrated that hemoglobin A(1c) level (β = .133, F = 5.490, P < .05) and waist circumference (β = .197, F = 11.954, P < .05) were independent predictors of the serum AIF-1 concentrations. The serum AIF-1 concentrations correlated with clinical and biochemical metabolic parameters. Allograft inflammatory factor-1 may be a significant predictor of activated macrophages as well as cardiovascular disease in humans.

The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight, glycemic control, insulin resistance, and inflammatory state in type 2 diabetes mellitus patients. Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >8.0%) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, tumor necrosis factor-α, adiponectin, vaspin, and high-sensitivity C-reactive protein. Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose, postprandial plasma glucose, lipid profile, leptin, tumor necrosis factor-α, and high-sensitivity C-reactive protein compared with sibutramine alone. Furthermore, there was a better improvement of body weight, HbA(1c), fasting plasma insulin, homeostasis model assessment of insulin resistance index, vaspin, and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone. Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect.

We studied whether serum complement C3 (C3) is an independent determinant of incident cardiometabolic risk (coronary heart disease [CHD], metabolic syndrome [MetS], and type 2 diabetes mellitus). A cohort of 1220 adults of a general population (age, 53 +/- 10.5 years) was evaluated prospectively at 3.3 years follow-up using Cox proportional hazard regressions. Cardiometabolic risk factors were measured. Metabolic syndrome was identified by Adult Treatment Panel III criteria modified for male abdominal obesity. The C3 levels were associated significantly and linearly with serum triglycerides, waist circumference, and C-reactive protein (CRP), and inversely with current smoking but not with the marker of insulin resistance. In regression models for incident MetS, increasing C3 quartiles strongly predicted MetS in women and in both sexes combined after adjusting for all 5 MetS components and other confounders. Circulating C3 significantly predicted in each sex incident CHD independent of age, smoking status, and presence of MetS. Even after entering CRP, C3 predicted CHD with a relative risk of 1.35 (95% confidence interval, 1.09-1.67) for 1-SD increment of C3 in the total sample. Complement C3 tended to contribute, additively to MetS, to the association with diabetes with a relative risk of 1.36 in women alone, not in men. In conclusion, elevated serum complement C3 is part of the MetS cluster and confers CHD risk, additively to MetS components and CRP, in a population in which MetS prevails. Levels contribute, additively to MetS, to the diabetes risk in women alone.

The synthetic compound NO-1886 (ibrolipim, [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase (LPL)-promoting agent that decreases plasma triglycerides, increases high-density lipoprotein cholesterol levels, and prevents fat accumulation in high fat-fed rats. However, the effect of NO-1886 on body weight, fat accumulation, and energy expenditure in ovariectomized (OVX) rats is not clear. The primary aim of this study was to ascertain whether NO-1886 ameliorated obesity in OVX rats and to examine the effects on fatty acid oxidation-related enzymes. NO-1886 decreased accumulation of visceral fat and suppressed the increase in body weight resulting from the ovariectomy. NO-1886 decreased the respiratory quotient and increased expression of the fatty acid translocase messenger RNA (mRNA) in the liver, soleus muscle, and mesenteric fat. NO-1886 also increased the expression of fatty acid-binding protein mRNA in the liver and soleus muscle and the expression of the uncoupling protein 3 (UCP3) mRNA in the heart, soleus muscle, and mesenteric fat, but not in the brown adipose tissue. Furthermore, NO-1886 did not affect UCP1 and UCP2 in brown adipose tissue. Therefore, amelioration of obesity by NO-1886 in OVX rats is possibly because of an the increased expression of fatty acid oxidation-related enzymes and UCP3, both of which are related to fatty acid transfer and fat use. Our study indicates that the LPL-promoting agent NO-1886 may be potentially beneficial in the treatment of obesity and obesity-linked health problems in postmenopausal women.

Angiopoietin-like protein 4 (ANGPTL4) represents an adipokine with metabolic effects within adipose tissue, such as inhibition of lipoprotein lipase activity and stimulation of lipolysis. These effects were convincingly demonstrated in mice. Therefore, we asked whether genetic variation within the ANGPTL4 gene contributes to prediabetic phenotypes, such as dyslipidemia, insulin resistance, or beta-cell dysfunction, in white subjects at an increased risk for type 2 diabetes mellitus. We genotyped 629 subjects with and without a family history of diabetes for the 4 single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 and performed correlational analyses with metabolic traits. For metabolic characterization, all subjects underwent an oral glucose tolerance test; a subset was additionally characterized by hyperinsulinemic-euglycemic clamp. The 4 SNPs rs4076317, rs2278236, rs1044250, and rs11672433 cover 100% of common genetic variation (minor allele frequency>or=0.05) within the ANGPTL4 gene (r2>or=0.8). None of these SNPs revealed significant correlation with anthropometric data (sex, age, body mass index, body fat, and waist-hip ratio) or with family history of diabetes. Furthermore, no reliable correlations were found with fasting triglycerides, fasting nonesterified fatty acids, and area under the curve of nonesterified fatty acids during oral glucose tolerance test or with parameters of insulin sensitivity and insulin secretion. Finally, haplotype analysis revealed the existence of 8 common diplotypes. None of these, however, was significantly correlated with insulin sensitivity, insulin secretion, or plasma lipid measures. We conclude that common genetic variation within the ANGPTL4 gene may not play a major role in the development of prediabetic phenotypes in our white population.

This study investigates the molecular mechanisms underlying the blood glucose-lowering effect of a 2-day very low-energy diet (VLED, 1883 kJ/d) in 12 obese (body mass index, 36.3 +/- 1.0 kg/m2 [mean +/- SEM]) type 2 diabetic (HbA(1C) 7.3% +/- 0.4%) patients simultaneously taken off all glucose-lowering therapy, including insulin. Endogenous glucose production (EGP) and glucose disposal ([6,6-2H2]-glucose) were measured before and after the VLED in basal and hyperinsulinemic (40 mU/m2 per minute) euglycemic conditions. Insulin signaling and expression of GLUT-4, FAT/CD36, and triglycerides were assessed in muscle biopsies, obtained before the clamp and after 30 minutes of hyperinsulinemia. Fasting plasma glucose decreased from 11.3 +/- 1.3 to 10.3 +/- 1.0 mmol/L because of a decreased basal EGP (14.2 +/- 1.0 to 11.9 +/- 0.7 micromol/kg per minute, P = .009). Insulin-stimulated glucose disposal did not change. No diet effect was found on the expression of the insulin receptor and insulin receptor substrate-1 or on phosphatidylinositol 3'-kinase activity, or on FAT/CD36 expression pattern, GLUT-4 translocation, or triglyceride distribution in either the basal or insulin-stimulated situation. Unexpectedly, basal PKB/Akt phosphorylation on T308 and S473 increased after the diet, at equal protein expression. In conclusion, a 2-day VLED lowers fasting plasma glucose via a decreased basal EGP without an effect on glucose disposal. Accordingly, no changes in activation of phosphatidylinositol 3'-kinase, triglyceride distribution, FAT/CD36 expression, and GLUT-4 translocation were found in skeletal muscle biopsies.

Glycogen synthase kinase-3 (GSK-3) protein levels and activity are elevated in skeletal muscle in type 2 diabetes, and inversely correlated with both glycogen synthase activity and insulin-stimulated glucose disposal. To explore this relationship, we have produced transgenic mice that overexpress human GSK-3beta in skeletal muscle. GSK-3beta transgenic mice were heavier, by up to 20% (P < .001), than their age-matched controls due to an increase in fat mass. The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). They were also hyperlipidemic with significantly raised serum cholesterol (+90%), nonesterified fatty acids (NEFAs) (+55%), and triglycerides (+170%). At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. Hepatic glycogen levels were significantly increased 4-fold. Female GSK-3beta transgenic mice did not develop glucose intolerance despite 7-fold overexpression of GSK-3beta protein and a 20% reduction in glycogen synthase activation in skeletal muscle. However, plasma NEFAs and muscle IRS-1 protein levels were unchanged in females. We conclude that overexpression of human GSK-3beta in skeletal muscle of male mice resulted in impaired glucose tolerance despite raised insulin levels, consistent with the possibility that elevated levels of GSK-3 in type 2 diabetes are partly responsible for insulin resistance.

Studies on the association of fatty acid-binding protein 2 (FABP2) A54T and promoter polymorphism, and type 2 diabetes mellitus, insulin, and triglyceride levels are controversial. The aim of this study was to investigate the interfering effect of FABP2 A54T and promoter polymorphism on the postprandial response to a mixed meal and an oral glucose load. Seven hundred men from the Metabolic Intervention Cohort Kiel underwent a standard glucose tolerance test and a standardized mixed meal test and were genotyped by use of the Taqman method. When calculated independently from promoter variability, postprandial triglyceride levels were significantly higher and postprandial insulin sensitivity (homeostasis model assessment index) was lower in homozygous carriers of FABP2 T54T compared with carriers of the FABP2 exon wild-type allele (FABP2 A54A and A54T). This confirms previous findings. The effect of the exon T54T genotype on triglyceride levels and insulin sensitivity, however, was dependent on promoter variability. We found a significant increase in postprandial triglyceride levels and a decrease in insulin sensitivity due to T54T only in the presence of the homozygous B genotype at the promoter polymorphism. Similar results were obtained after oral glucose tolerance test. Reporter gene assays indicated a higher responsiveness to peroxisome proliferator-activating receptor-gamma (PPAR-gamma)/retinoid X receptor (RXR) of FABP2 promoter B vs promoter A. Synergism between a higher inducibility of FABP2 expression and a higher activity of T54 variant may explain higher postprandial triglycerides in case of combined genotype (promoter B + T54). This interference and different linkage disequilibrium between FABP2 exon and promoter polymorphisms may explain the different results obtained in different cohorts.

Little is known about the effects of menopause and hormone replacement therapy (HRT) on adiponectin production. The objectives of the study were to compare levels of serum adiponectin in post- and premenopausal women, to test whether adiponectin levels are related to endogenous estradiol and sex hormone-binding globulin (SHBG) levels, to determine whether HRT influences serum adiponectin, and to investigate relationships of adiponectin levels with cardiovascular risk factors. One hundred four women matched for body mass index were enrolled in this study, and among them were 34 postmenopausal HRT nonusers, 34 postmenopausal HRT users, and 36 premenopausal healthy women with regular menstrual cycles. We evaluated waist circumference and waist-to-hip ratio (WHR) in each women. Serum was assayed for adiponectin, estradiol, SHBG, triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol, and fasting glucose levels. Post- and premenopausal women showed no significant differences in adiponectin and SHBG concentrations. There were no differences in serum adiponectin levels between postmenopusal HRT nonusers and users; however, SHBG concentrations were higher in HRT users. The simple linear regression analyses of all studied women indicated that serum adiponectin was negatively correlated with body mass index, waist circumference, WHR, and TG levels. Positive correlation was observed between adiponectin and high-density lipoprotein cholesterol as well as between adiponectin and SHBG levels. There were no relationships between adiponectin and estradiol levels in all studied women and among subgroups. Multiple regression analysis showed that WHR and TG were significant independent predictors of serum adiponectin. In conclusion, serum adiponectin levels are not influenced by menopausal status or serum estradiol levels. Exogenous estrogen treatment does not significantly affect serum adiponectin concentrations.

Apelin has been proposed as a novel beneficial adipokine that is related to insulin resistance, cardiovascular risk factors, and obesity. However, findings in humans are controversial; and longitudinal analyses in childhood are still missing. We compared apelin levels between 80 obese and 40 lean children of the same age, sex, and pubertal stage. In addition, we analyzed the relationships between apelin levels and weight status (as standard deviation of body mass index [SDS-BMI]), body fat, insulin resistance (homeostasis model assessment [HOMA]), leptin, and cardiovascular risk factors associated with obesity (waist circumference, blood pressure, lipids, and adiponectin) in 80 obese children before and after participating in a 1-year lifestyle intervention. Apelin levels did not differ significantly (P = .061) between obese (1.50 ± 0.47 ng/mL, mean ± SD) and lean children (1.67 ± 0.49 ng/mL). Apelin concentrations were not significantly related to age, pubertal stage, SDS-BMI, body fat, leptin, or any cardiovascular risk factor. In longitudinal analyses, no significant correlations were found between changes of apelin and changes of SDS-BMI, body fat, leptin, HOMA, or any cardiovascular risk factor. Adiponectin, HOMA, blood pressure, waist circumference, and triglycerides improved significantly in 39 obese children with SDS-BMI reduction, whereas leptin decreased significantly and apelin did not change significantly in these children. In 41 children with increase of SDS-BMI, no significant changes were observed in 1-year follow-up period. This is the first study demonstrating that weight loss in obese children was not associated with a change of apelin concentrations. Our data do not support a significant relationship in childhood between apelin on one hand and leptin, HOMA, cardiovascular risk factors, or weight status on the other.