Morphological and molecular characterization of GALNT2-mediated adipogenesis.

3T3L1 mouse pre-adipocytes develop into adipocytes differently in response to GALNT2 overexpression or to stimulation with rosiglitazone, a reference inducer of adipogenesis. To investigate the biology of alternative pathways of adipogenesis, we studied lipid droplets (LD) morphology, chromatin organization, and gene expression in GALNT2- versus rosiglitazone-induced 3T3L1 adipogenesis. 3T3L1 overexpressing either GALNT2 (GALNT2) or GFP and treated with rosiglitazone (GFPR) were differentiated into adipocytes.

GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling.

Background/objectives: A better understanding of adipose tissue biology is crucial to tackle insulin resistance and eventually coronary heart disease and diabetes, leading causes of morbidity and mortality worldwide. GALNT2, a GalNAc-transferase, positively modulates insulin signaling in human liver cells by down-regulating ENPP1, an insulin signaling inhibitor. GALNT2 expression is increased in adipose tissue of obese as compared to that of non-obese individuals.

Suggestive evidence of a multi-cytokine resistin pathway in humans and its role on cardiovascular events in high-risk individuals.

In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine "resistin pathway". We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMA, triglycerides, HDL-cholesterol, systolic and diastolic blood pressure data were available and in 353 patients with type 2 diabetes and coronary artery disease from the Gargano Heart Study (GHS)-prospective design (follow-up 5.

Serum resistin is causally related to mortality risk in patients with type 2 diabetes: preliminary evidences from genetic data.

Resistin has been firmly associated with all-cause mortality. We investigated, whether, in patients with type 2 diabetes (T2D), this association is sustained by a cause-effect relationship. A genotype risk score (GRS), created by summing the number of resistin increasing alleles of two genome-wide association studies (GWAS)-derived single nucleotide polymorphisms (SNPs), serum resistin measurements and all-cause death records were obtained in 1,479 (403 events/12,454 person-years), patients with T2D from three cohorts, Gargano Heart Study-prospective design (n = 350), Gargano Mortality Study (n = 698) and Foggia Mortality Study (n = 431), from Italy.

The combined effect of adiponectin and resistin on all-cause mortality in patients with type 2 diabetes: Evidence of synergism with abdominal adiposity.

Background And Aims: While elevated serum adiponectin and resistin levels have been singly associated with all-cause mortality in patients with type 2 diabetes (T2D), their combined effect has never been studied. We investigated such joint effect in patients with T2D and its possible modulation by several demographic and clinical conditions, known to affect per se mortality rate.

Methods: Patients with T2D from the Gargano Mortality Study (GMS; N = 895, follow-up = 10.

Evidence of a causal relationship between high serum adiponectin levels and increased cardiovascular mortality rate in patients with type 2 diabetes.

Background: Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been repeatedly reported as an independent positive predictor of cardiovascular mortality.

Methods: A Mendelian randomization approach was used, in order to evaluate whether such counterintuitive association recognizes a cause-effect relationship. To this purpose, single nucleotide polymorphism rs822354 in the ADIPOQ locus which has been previously associated with serum adiponectin at genome-wide level, was used as an instrument variable.

The paradoxical association of adiponectin with mortality rate in patients with type 2 diabetes: evidence of synergism with kidney function.

Background: The paradoxical relationship between high adiponectin and increased mortality, described in several clinical subsets, has been reported only once in type 2 diabetes (T2D) and only in selected elderly patients. We investigated this relationship in unselected patients with T2D and, then, addressed its possible modulation by several demographic and clinical conditions, known to affect per se mortality rate.

Methods: Patients from the Gargano Mortality Study (GMS; N = 897, follow-up = 10.

Serum Adiponectin and Glomerular Filtration Rate in Patients with Type 2 Diabetes.

High serum adiponectin has been increased in several conditions of kidney disease. Only sparse and conflicting results have been reported in patients with type 2 diabetes (T2D), a subgroup of individuals who are at high risk for renal dysfunction. The aim of this study was to fill up this gap of knowledge by investigating such association in a large sample of Italian diabetic patients.

Serum resistin and glomerular filtration rate in patients with type 2 diabetes.

Background: High serum levels of the pro-inflammatory adipokine resistin have been associated with decreased renal function in the general population. The goal of this study was to investigate whether such association is also present among diabetic subjects, who are at increased risk of renal function loss.

Methods: The cross-sectional association between serum resistin levels and estimated glomerular filtration rate (eGFR) was investigated in 1,560 type 2 diabetic (T2D) patients of European ancestry comprised in two different cohorts: 762 patients from San Giovanni Rotondo (SGR; Italy) and 798 patients from Boston (US).

Circulating adiponectin and cardiovascular mortality in patients with type 2 diabetes mellitus: evidence of sexual dimorphism.

Background: The pathogenesis of cardiovascular (CV) mortality, whose rate is increased in type 2 diabetes, is poorly understood.

Methods: Three prospective cohorts were analyzed: 1) Gargano Heart Study (GHS; 359 patients, 58 events/1,934 person-years; py); 2) Health Professional Follow-up Study (HPFS; 833 men, 146 events/10,024 py); 3) Nurses' Health Study (NHS; 902 women, 144 events/15,074 py).

Results: In GHS serum adiponectin predicted CV mortality in men (hazard ratio, HR, and 95% CI per standard deviation, SD, increment = 1.

Serum resistin, cardiovascular disease and all-cause mortality in patients with type 2 diabetes.

Background: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes.

Methods: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies.

Serum resistin and kidney function: a family-based study in non-diabetic, untreated individuals.

Background: High serum resistin levels have been associated with kidney dysfunction. Most of these studies have been carried out in individuals with severe kidney impairment, diabetes, cardiovascular disease and related treatments. Thus, the observed association might have been influenced by these confounders.

Novel locus FER is associated with serum HMW adiponectin levels.

Objective: High molecular weight (HMW) adiponectin is a predominant isoform of circulating adiponectin and has been related to type 2 diabetes. Previous linkage studies suggest that different genetic components might be involved in determining HMW and total adiponectin levels.

Research Design And Methods: We performed a genome-wide association study (GWAS) of serum HMW adiponectin levels in individuals of European ancestry drawn from the Nurses' Health Study (NHS) (N = 1,591).

Akt2 Gene common allelic variants in insulin resistance and the metabolic syndrome.

Background And Aim: Several lines of evidence indicate that glucose homeostasis may be under the control of Akt2 and it can therefore be seen as a candidate gene for human insulin resistance (IR) and related phenotypes. The aim of our study was the identification of Akt2 common allelic variants that might modulate susceptibility to IR and related metabolic abnormalities.

Methods And Results: The Akt2 gene (exons, 5' and 3' regulatory regions) was re-sequenced in samples of 50 blood donors from the Gargano region.

The -318 C>G single-nucleotide polymorphism in GNAI2 gene promoter region impairs transcriptional activity through specific binding of Sp1 transcription factor and is associated with high blood pressure in Caucasians from Italy.

Inhibiting Galpha subunit 2 protein, which is encoded by the GNAI2 gene, is suggested to be pathogenic for essential hypertension and/or insulin resistance. The aim of this study was to determine whether GNAI2 variations modulate the risk for these abnormalities. Seven single-nucleotide polymorphisms (SNP) at the GNAI2 locus were identified.