The mtDNA 15497 G/A polymorphism in cytochrome b in severe obese subjects from Southern Italy.

Background and aim: A large number of mitochondrial DNA (mtDNA) mutations have been implicated in degenerative diseases and aging. The aim of this study was to evaluate whether the 15497 G/A mtDNA polymorphism (G251S) in the cytochrome b subunit of respiratory complex III, which has been associated with obesity-related variables and lipid metabolism in a Japanese population, is associated with severe obesity also in adult Caucasians from southern Italy. Methods and results: Unrelated severely obese patients (n Z 317; BMI > 40 kg/m2) and controls (n Z 217; BMI < 25 kg/m2) from Southern Italy were genotyped by allelic discrimination TaqMan assay for the 15497 G/A mtDNA polymorphism. In obese patients fasting serum total cholesterol, triglycerides, HDL-cholesterol and glucose were measured enzymatically and sitting blood pressure and heart rate were also collected. Mean levels of total cholesterol, triglycerides and glucose were below the upper reference limit for healthy subjects. Female obese subjects showed lower levels of blood pressure and heart rate and higher levels of HDL cholesterol than male obese patients (P < 0.001). All the control subjects and 315/317 severely obese patients were homozygous for the G allele (wild type), whereas only 2/317, were females homozygous for the A allele. Conclusions: The mtDNA 15497 G/A polymorphism in cytochrome b was present in 0.6% obese subjects, two females whose lipid parameters and BMI were similar to those of the overall group. Therefore, this mutation may appear to contribute in rare instances to severe obesity but does not explain the majority of cases in our population. A more extensive genetic haplogroup characterization is required to identify associations to obesity in Caucasians

Sequence Analysis of the UCP1 Gene in a Severe Obese Population from Southern Italy

Brown adipose tissue, where Uncoupling Protein 1 (UCP1) activity uncouples mitochondrial respiration, is an important site of facultative energy expenditure. This tissue may normally function to prevent obesity. Our aim was to investigate by sequence analysis the presence of UCP1 gene variations that may be associated with obesity. We studied 100 severe obese adults (BMI > 40 kg/m2) and 100 normal-weight control subjects (BMI range = 19–24.9 kg/m2). We identified 7 variations in the promoter region, 4 in the intronic region and 4 in the exonic region. Globally, 72% of obese patients bore UCP1 polymorphisms. Among UCP1 variants, g.IVS4−208T>G SNP was associated with obesity (OR: 1.77; 95% CI = 1.26–2.50; P = .001). Further, obese patients bearing the g.−451C>T (CT+TT) or the g.940G>A (GA+AA) genotypes showed a higher BMI than not polymorphic obese patients (P = .008 and P = .043, resp.). In conclusion, UCP1 SNPs could represent “thrifty” factors that promote energy storage in prone subjects

Preliminary data on the relationship between circulating levels of Sirtuin 4, anthropometric and metabolic parameters in obese subjects according to growth hormone/insulin-like growth factor-1 status

Background: The main components of GH/insulin-like growth factor (IGF)-1 axis and Sirtuin 4 (Sirt4), highly expressed in liver and skeletal muscle mitochondria, serve as active regulators of mitochondrial oxidative capacity with opposite functions. In obesity both GH/IGF-1 status and serum Sirt4 levels, likely mirroring its reduced mitochondrial expression, might be altered. Objective: To evaluate the association between circulating levels of Sirt4, body composition, metabolic parameters and cardio-metabolic risk profile in obese patients according to their different GH/IGF-1 status. Design: Cross-sectional study with measurement of serum Sirt4, GH after GH releasing hormone (GHRH)+Arginine test, IGF-1 and assessment of body composition, glucose and lipid metabolism in 50 class II-III obese subjects (BMI 35.6 to 62.1kg/m2) and 15 normal weight subjects. Low GH secretion and IGF-1 were defined using pre-determined cutoff-points. The Homeostatic Metabolic Assessment of insulin resistance index and Visceral adiposity index were also calculated. The association of Sirt4 with peak stimulated GH and IGF-1, body composition, metabolic parameters and cardio-metabolic risk profile was assessed. Results: Serum Sirt4 was inversely related to anthropometric and metabolic parameters and positively related to peak GH and IGF-1. After adjusting for peak GH and IGF-1, the relationships between Sirt4 and BMI became not significant. At multiple regression analysis IGF-1 (p < 0.001) was the independent predictor for Sirt4. Conclusion: There was a close relationship between low IGF-1 and low serum Sirt4. This observation suggested that in obese patients, low GH/IGF-1 status was likely associated with a major compensatory decrease in circulating levels of Sirt4 to oppose to its negative regulator effect on mitochondrial oxidative capacity

Young adult obese subjects with and without insulin resistance: what is the role of chronic inflammation and how to weigh it non-invasively?

<p>Abstract</p> <p>Background</p> <p>Obesity is a leading risk factor for metabolic syndrome whose further expression is non-alcoholic fatty liver disease. Metabolic syndrome is associated with a proinflammatory state that contributes to insulin resistance. Finally, a "metabolically benign obesity" that is not accompanied by insulin resistance has recently been postulated to exist.</p> <p>Aim</p> <p>To find whether any inflammation markers were independently associated with the presence of insulin resistance, evaluating specific anthropometric, ultrasonographic and laboratory parameters in a population of young adult obese subjects.</p> <p>Methods</p> <p>Of forty two young individuals, divided into two groups (with or without insulin resistance), were studied serum C-reactive protein and fibrinogen as indexes of chronic pro-inflammatory status. Body mass index, waist circumference and metabolic syndrome presence were assessed as part of the metabolic evaluation. Ultrasonography weighted visceral and subcutaneous abdominal fat thickness, spleen size as longitudinal diameter and liver hyperechogenicity.</p> <p>Results and Discussion</p> <p>Serum C-reactive protein and fibrinogen as well as spleen longitudinal diameter were significantly increased in the obese young with insulin resistance compared to non-insulin resistance group. Insulin resistance was significantly associated with hepatic steatosis score at sonography (r = 0.33, P = 0.03), spleen longitudinal diameter (r = 0.35, P = 0.02) and C-reactive protein (r = 0.38, P = 0.01), but not with body mass index, visceral or subcutaneous abdominal adipose tissue, waist circumference and fibrinogen (P = 0.18, 0.46, 0.33, 0.37 and 0.4, respectively). Steatosis score at sonography was well associated with spleen volume (rho = 0.40, P = 0.01) and C-reactive protein levels (rho = 0.49, P = 0.002). Metabolic syndrome was much more frequent in obese patients with insulin resistance. These findings show that in young adults the only abdominal adiposity without insulin resistance, plays a scarce role in determining hepatic steatosis as well as metabolic syndrome.</p> <p>Conclusion</p> <p>Increases in spleen size and CRP levels represent a reliable tool in diagnosing insulin resistance.</p

Are hepatic steatosis and carotid intima media thickness associated in obese patients with normal or slightly elevated gamma-glutamyl-transferase?

<p>Abstract</p> <p>Background</p> <p>Hepatic steatosis (HS) has been associated with obesity and metabolic syndrome (MS), conditions carrying a high risk of coronary artery disease. We aimed to determine whether HS was an independent factor of atherogenic risk beyond its association with MS and its components.</p> <p>Methods</p> <p>We assessed the circulating levels of the heat shock protein-70 (HSP-70), a chaperone involved in inflammation, endoplasmic reticulum stress and apoptosis at liver and endothelial level and the gamma-glutamyl transferase activity (γ-GT) correlating them to carotid intima-media thickness (IMT), along with lipid profile, HOMA, C-reactive protein, fibrinogen, ferritin, adiposity type as well as spleen volume in 52 obese pts with grade 1, 128 with grade 2, and 20 with grade 3 of HS evaluated by sonography.</p> <p>Results</p> <p>Patients with different grade of HS demonstrated overlapping HSP-70 levels; similarly performed obese subjects regarding IMT. Using multiple regression analysis, IMT was predicted by age, visceral adiposity and by HOMA (β = 0.50, <it>p </it>< 0.0001, β = 0.30, <it>p </it>= 0.01 and β = 0.18, <it>p </it>= 0.048 respectively, while the severity of HS was predicted by visceral and subcutaneous adiposity and HOMA (β = 0.50, <it>p </it>< 0.0001 and β = 0.27, <it>p </it>= 0.001 and β = 0.18, <it>p </it>= 0.024, respectively).</p> <p>Conclusion</p> <p>In our series of patients with normal or mild elevation of γ-GT, the severity of HS does not entail higher IMT, which may be linked to MS stigmata.</p