Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

OBJECTIVES: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. METHODS: Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. RESULTS: HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). CONCLUSIONS: HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.

Mannose-binding lectin gene polymorphisms are associated with gestational diabetes mellitus.

Insulin resistance is a feature of gestational diabetes mellitus (GDM). Inverse correlations between indexes of insulin sensitivity and serum markers of inflammation have been observed and, particularly, TNF-alpha has been shown to be associated with the appearance of insulin resistance in pregnancy. Mannose-binding lectin (MBL) is a protein member of the collectin family. Its deficiency is genetically determined and predisposes to recurrent infections and chronic inflammatory diseases. To test the hypothesis that a genetic predisposition to a proinflammatory state could favor the appearance of GDM during pregnancy, we studied R52C and G54D polymorphisms of MBL2 gene and plasma MBL levels from 105 consecutive GDM women and 173 healthy pregnant women. An association was found between G54D and GDM [odds ratio, 2.03 (1.18-3.49); P < 0.01], and this association remained significant when the presence of both mutated alleles was considered [odds ratio, 1.76 (1.04-2.96); P < 0.05] but not for the R52C. GDM patients who carried the G54D mutation required insulin therapy more frequently (56.4 vs. 30.4%, chi(2) =5.83; P = 0.027) and had heavier infants (3326.4 +/- 546.9 vs. 3087.5 +/- 395.5 g; P < 0.05) than GDM women homozygous for the wild-type allele. An inverse correlation in GDM patients between neonatal weight and plasma MBL levels (r = -0.320; P = 0.002) was found, remaining significant after adjustment for confounding variables. In conclusion, pregnant women bearing the G54D MBL allele have a greater risk for developing GDM and having heavier infants.

Study of the potential association of adipose tissue GLP-1 receptor with obesity and insulin resistance.

The increase in glucagon-like peptide-1 (GLP-1) activity has emerged as a useful therapeutic tool for the treatment of type 2 diabetes mellitus. The actions of GLP-1 on ß-cells and the nervous and digestive systems are well known. The action of this peptide in adipose tissue (AT), however, is still poorly defined. Furthermore, no relationship has been established between GLP-1 receptor (GLP-1R) in AT and obesity and insulin resistance (IR). We provide evidence for the presence of this receptor in AT and show that its mRNA and protein expressions are increased in visceral adipose depots from morbidly obese patients with a high degree of IR. Experiments with the 3T3-L1 cell line showed the lipolytic and lipogenic dose-dependent effect of GLP-1. Moreover, GLP-1 stimulated lipolysis in 3T3-L1 adipocytes in a receptor-dependent manner involving downstream adenylate cyclase/cAMP signaling. Our data also demonstrate that the expression of the GLP-1R in AT correlated positively with the homeostasis model assessment index in obese IR subjects. Furthermore, prospective studies carried out with patients that underwent biliopancreatic diversion surgery showed that subjects with high levels of GLP-1R expression in AT, which indicates a deficit of GLP-1 in this tissue, were those whose insulin sensitivity improved after surgery, suggesting the potential relationship between AT GLP-1R and insulin sensitivity amelioration in obese subjects. Altogether these results indicate that the GLP-1/GLP-1R system in AT represents another potential candidate for improving insulin sensitivity in obese patients.

Distribution and determinants of adiponectin, resistin and ghrelin in a randomly selected healthy population.

OBJECTIVE: Adiponectin, resistin, ghrelin and the IGF-I system seem to play an important role in the regulation of body composition throughout life, but the mechanisms are not well understood. The aim of our study was to analyse the distribution among sexes and all decades of the adult life of adiponectin, resistin and ghrelin and their relationship with anthropometric, body composition parameters and the IGF-I system. SUBJECTS: One hundred and thirty-four men and 127 healthy women were included in the study. MEASUREMENTS: Plasma concentration of adiponectin, resistin, ghrelin, total IGF-I, free IGF-I and IGFBP-3 were determined in all subjects. Body composition was evaluated by bioelectrical impedance. RESULTS: Resistin and ghrelin were not affected by age. Plasma adiponectin correlated negatively with age, body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), fat mass (FM) and body fat (BF) in men. Adiponectin correlated negatively with WHR and positively with free IGF-I in women. Resistin correlated positively with BMI and WC only in men, and ghrelin correlated positively with WC, BMI and FM and negatively with free IGF-I in men. In multiple regression analysis adiponectin remained associated with WHR (beta=-0.19, P=0.01) in women. Resistin was positively associated with BMI (beta=0.30, P=0.003) in women and ghrelin was negatively related to free IGF-I (beta=-0.158, P=0.019) in men. CONCLUSIONS: Plasma adiponectin declines with age and is negatively associated with FM in men. Our data suggest the existence of a positive correlation of adiponectin and the IGF-I axis in women and of an inverse relationship between ghrelin and the IGF-I system in men.