Biomedical subjects

E Dalla Nora

Publications and source records attributed to E Dalla Nora.

7 recordsLinked to original sources

PubMed2006

WNT10B mutations in human obesity.

AIMS/HYPOTHESIS: Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. SUBJECTS AND METHODS: We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. RESULTS: One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. CONCLUSIONS/INTERPRETATION: These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations.

Adipocytes↗

PubMed2005

Mouse models of PPAR-gamma deficiency: dissecting PPAR-gamma's role in metabolic homoeostasis.

The identification of humans with mutations in PPAR-gamma (peroxisome-proliferator-activated receptor-gamma) has underlined its importance in the pathogenesis of the metabolic syndrome. Genetically modified mice provide powerful tools to dissect the mechanisms by which PPAR-gamma regulates metabolic processes. Ablation of PPAR-gamma in vivo is lethal and thus dissection of PPAR-gamma function using mouse models has relied on the development of tissue and isoform-specific ablation and mouse models of human mutations. These models exhibit phenotypes of partial PPAR-gamma impairment and are useful to elucidate how PPAR-gamma regulates specific metabolic processes. These murine models have confirmed the involvement of PPAR-gamma in adipose tissue development, maintenance and distribution. The mechanism involved in PPAR-gamma regulation of glucose homoeostasis is obscure as both agonism and partial impairment of PPAR-gamma increase insulin sensitivity. While adipose tissue is likely to be the primary target for the insulin-sensitizing effects of PPAR-gamma, some murine models suggest PPAR-gamma expressed outside adipose tissue may also contribute actively to maintain glucose homoeostasis. Interestingly, mutations in PPAR-gamma that cause severe insulin resistance in humans when expressed in mice do not result in insulin insensitivity. However, these murine models can recapitulate the effects in fuel partitioning, post-prandial lipid handling and vasculature dysfunction observed in humans. In summary, these murine models of PPAR-gamma have provided useful in vivo systems to dissect the function of PPAR-gamma, but additionally have revealed a picture of complexity. These models have confirmed a key role for PPAR-gamma in the metabolic syndrome; however, they challenge the concept that insulin resistance is the main factor linking the clinical manifestations of the metabolic syndrome.

Adipose Tissue↗

PubMed2004

Trace elements and cognitive impairment: an elderly cohort study.

Dementia is one of the most pressing public health problems with social and economic implication. The form called cognitive impairment non-dementia (CIND)represents a subclinical phase of dementia. Different studies have shown a possible effect of micro- and macro-nutrients on cognitive function. Trace elements, being involved in metabolic processes and redox reactions in the central nervous system (CNS), could influence the cognitive functions. This study evaluated the presence of an eventual correlation between serum trace element concentrations and cognitive function in a group of subjects with CIND and manifest dementia (Alzheimer dementia = AD, and vascular dementia = VaD), and compared them with a control group. Thirty -five patients were enrolled in this study. Each patient underwent a clinical and biochemical examination. We also performed a neuropsychological and functional assessment (the Milan overall dementia assessment = MODA, activities of daily living = ADL, and instrumental activities of daily living = IADL), and a computerized tomographic (CT) cerebral scan. Patients were than divided in 4 groups according to the obtained diagnosis (Controls, CIND, AD, VaD). The presence of any acute or chronic conditions, affecting cognitive functions, was considered as exclusion criteria. A blood sample was collected to determine iron (Fe), zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), chromium (Cr), copper (Cu),molybdenum (Mo) and aluminium (Al) serum concentrations (chromatographic,spectrophotometric methods). In our cohort we found a positive correlation between cognitive function, expressed as the MODA score, and Se, Cr, Co and Fe serum levels,while a negative correlation was observed between MODA score, Cu and Al serum levels.Moreover, some statistically significant differences in Se, Cr, Co, Cu and Al concentrations were found among the groups. According to these results, we may suppose that Se, Cr and Co protect cognitive function, Cu influences the evolution of cognitive impairment, while Al contributes to the pathogenesis of AD.

Activities of Daily Living↗

PubMed2004

Changes in muscle myostatin expression in obese subjects after weight loss.

Myostatin is a member of transforming growth factor-beta superfamily that plays an important inhibitory role during muscle development; in fact mutations of myostatin gene result in a hypermuscular phenotype. Moreover myostatin-deficient mice have a significant reduction in fat depots and a depression of adipogenesis. Little is known about myostatin function in muscle growth regulation in humans and in particular during caloric restriction. In the present work we quantified by real-time RT-PCR myostatin expression in muscle biopsies of a group of morbidly obese patients before and after weight loss obtained by biliopancreatic diversion (BPD). The patients reduced body weight by 38.9%, mostly due to fat-mass loss, showing also a significant reduction in the 24-hour EE as assessed by the respiratory chamber. Myostatin mRNA levels result clearly decreased after weight loss, suggesting a role in counteracting the progressive decline of muscle mass after BPD. Myostatin may provide therefore another mechanistic explanation for the control of energy partitioning between protein and fat, working against muscle wasting. Our data suggest that myostatin might represent an important regulator of skeletal muscle size also in conditions of food restriction in obese subjects.

Body Composition↗

PubMed2003

Atorvastatin improves metabolic control and endothelial function in type 2 diabetic patients: a placebo-controlled study.

Several pieces of evidence support a role of inflammatory processes in the pathogenesis of atherosclerosis; it is also known that endothelial dysfunction is the initial lesion of the atherosclerotic process. Among other markers of endothelial dysfunction, some adhesion molecules seem to play an interesting role. The aim of the present study was to evaluate the effect of atorvastatin vs placebo on some indexes of leukocytes adhesion in a group of Type 2 diabetic patients. Twenty-five Type 2 diabetic patients free from microangiopathic complications and with LDL-cholesterol lower than 180 mg/dl were randomized to receive either atorvastatin (T2DA) or placebo (T2Dp) for twelve months. BMI, fasting plasma glucose, glycated hemoglobin (HbA1c), albumin excretion rate (AER), lipid profile, and serum concentrations of vascular cell adhesion molecule-1 (VCAM1), E-selectin and cadherin-5 were measured at baseline and at the end of the follow-up. At T0 E-selectin was 16 +/- 6 ng/ml in T2DA and 17 +/- 13 in T2Dp; VCAM1 was 413 +/- 112 ng/ml in T2DA and 411 +/- 112 in T2Dp. At T12 VCAM1 and E-selectin did not vary in T2Dp, while a significant reduction was observed in T2DA (VCAM1 275 +/- 104 ng/ml and E-selectin 8 +/- 3 ng/ml; p < 0.001 and p < 0.01, respectively). T2DA also showed a reduction of total and LDL cholesterol and an improved glycemic control respect to T2Dp. Hypolipidemic therapy was the strongest independent predictor of the cytokines variations along the time. These results confirm the role of statins in modulating endothelial function also in Type 2 diabetes, outlining a therapeutic role of these molecules probably independent from the hypolipidemic effect.

Adult↗

PubMed2003

Effect of metabolic control on homocysteine levels in type 2 diabetic patients: a 3-year follow-up.

OBJECTIVES: Hyperhomocysteinaemia has emerged as a novel risk factor for cardiovascular disease. The determinants of total homocysteine (tHcy) levels in type 2 diabetic patients (D2p) have not been studied in detail. We examined prospectively the effect of different degrees of metabolic control on plasma tHcy in D2p with preserved kidney function. SUBJECTS AND MAIN OUTCOME MEASUREMENTS: Ninety-five D2p were studied. Clinical parameters, fasting plasma glucose, HbA1c, serum lipids, blood urea nitrogen (BUN) and creatinine, vitamin B12 and folate and tHcy were measured at the baseline and after 36 months. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism was also determined. Subjects were categorized according to deltaHbA1c into group A (+/-1 point), B (>1 point increase) or C (>1 point decrease). RESULTS: Total homocysteine was reduced in subjects whose HbA1c decreased with time, whilst patients showing a worsened metabolic control had an increased tHcy in respect to baseline. A larger response to the improved metabolic control in terms of tHcy reduction was noted in wild type patients versus those homozygous for the mutation. A multivariate analysis revealed MTHFR polymorphism and HbA1c as strong determinants of changes in tHcy with time. CONCLUSIONS: The findings suggest that in D2p tHcy decreases even with modest improvement of glycaemic control; moreover patients homozygous for the MTHFR C677T mutation show the largest changes in tHcy levels with concomitant changing of HbA1c. These results define a further mechanism through which hyperglycaemia might promote cardiovascular damage in diabetic patients.

Aged↗

PubMed2001

Role of diabetes in influencing leptin concentration in elderly overweight patients.

BACKGROUND: Leptin, the product of the ob gene, could have a significant role in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. However, it is still debated whether different degrees of glucose tolerance may affect plasma leptin concentrations in obese patients. OBJECTIVE: To investigate whether diabetes might influence leptin concentrations in obese patients. METHODS: We evaluated clinical parameters, anthropometric measures, and sex hormones, fasting plasma leptin, glucose and insulin concentrations in 100 elderly obese diabetic patients and 100 obese non-diabetic control individuals matched for age and sex. RESULTS: After adjustment for age and fat mass, plasma leptin concentrations did not differ between diabetic and non-diabetic obese individuals, in both men and women. In all patients leptin was significantly related to body mass index, fat mass and the homeostasis model insulin resistance index; moreover we observed a significant relationship with fasting plasma glucose and age in diabetic obese women, and with blood pressure values and testosterone concentrations in diabetic obese men. Multiple regression analysis revealed age and fasting plasma glucose to be the only independent determinants of fasting plasma leptin in diabetic obese women. CONCLUSIONS: These data suggest that leptin concentrations do not differ between obese diabetic and obese non-diabetic elderly patients. Among correlates of the metabolic syndrome, systolic pressure seems to be related to leptin only in men. In the postmenopausal or andropausal status, sex hormones are related to leptin concentrations only in diabetic men; in diabetic women, however, high glucose seems to be relevant in maintaining the same leptin concentrations as in non-diabetic women with similar degree of obesity.

Age Factors↗