-
Maurizio Soresi,
Davide Noto,
Angelo B Cefalù,
Scipione Martini,
Giovanni Battista Vigna,
Maurizio Fonda,
Enzo Manzato, Luigi Cattin,
Renato Fellin,
Maurizio R Averna,
Alberto Notarbartolo
[show abstract]
[hide abstract]
ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is associated with all the components of metabolic syndrome (MS) and might to be considered an additional component of MS itself. The Italian Society for the Study of Atherosclerosis (SISA) in 2005 started a research project aimed to study the NAFLD, using ultrasound (US), in nondiabetic MS subjects matching at least one of the ATP III criteria for HDL-C or triglycerides [TG]. Prevalence of US-NAFLD and its associated risk factors and prevalence of hypertransaminasemia and its possible determinants were evaluated. NAFLD prevalence was 0.78. Men with steatosis compared to men without steatosis were younger (P < 0.05) with higher TG (P < 0.03), homeostasis model assessment insulin resistance (HOMA-R) (P < 0.003), and visceral fat thickness (VFT) (P < 0.0001). Women with steatosis showed higher TG (P < 0.05), HOMA-R (P < 0.04), VFT (P < 0.0001), and lower age (P < 0.05). At multivariate analyses, VFT (P < 0.0001), HOMA-R (P < 0.02), and TG/HDL (P < 0.05) were associated with severity of NAFLD. Age (P < 0.05), LogTG (P < 0.005), and VFT (P < 0.01) were associated with higher ALT. The US prevalence of steatosis in this study (0.78) is the highest reported in patients with MS. Considering the exclusion of severe obese and diabetic patients and the recruitment criteria, this finding highlights the prominent role played by the alterations of lipid metabolism in the pathogenesis of NAFLD.
Acta Diabetologica 06/2012; · 2.78 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The purposes of this study were to describe a newly developed algorithm that estimates the glucose supplement on a patient- and situation-specific basis and to test whether these amounts would be appropriate for maintaining blood glucose levels within the recommended range in exercising type 1 diabetic patients.
The algorithm first estimates the overall amount of glucose oxidized during exercise on the basis of the patient's physical fitness, exercise intensity, and duration. The amount of supplemental CHO to be consumed before or during the effort represents a fraction of the burned quantity depending on the patient's usual therapy and insulin sensitivity and on the time of day the exercise is performed. The algorithm was tested in 27 patients by comparing the estimated amounts of supplemental CHO with the actual amounts required to complete 1-h constant-intensity walks. Each patient performed three trials, each of which started at different time intervals after insulin injection (81 walks were performed overall). Glycemia was tested every 15 min.
In 70.4% of the walks, independent of the time of day, the amount of CHO estimated by the algorithm would be adequate to allow the patients to complete the exercise with a glucose level within the selected thresholds (i.e., 3.9-10 mmol·L(-1)).
The algorithm provided a satisfactory estimate of the CHO needed to complete the exercises. Although the performance of the algorithm still requires testing for different exercise intensities, durations, and modalities, the results indicate its potential usefulness as a tool for preventing immediate exercise-induced glycemic imbalances (i.e., during exercise) in type 1 diabetic patients, in particular for spontaneous physical activities not planned in advance, thus allowing all insulin-dependent patients to safely enjoy the benefits of exercise.
Medicine and science in sports and exercise 01/2011; 43(1):2-11. · 3.71 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-µg s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P = NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity.
PLoS ONE 01/2011; 6(10):e26224. · 4.09 Impact Factor
-
Rocco Barazzoni,
Michela Zanetti,
Mauro Sturnega,
Marco Stebel,
Annamaria Semolic,
Alessia Pirulli,
Pierandrea Vinci,
Lorena Zentilin,
Mauro Giacca, Luigi Cattin,
Gianfranco Guarnieri
[show abstract]
[hide abstract]
ABSTRACT: Involvement of insulin in diabetes-associated liver triglyceride deposition and its potential pathways remain incompletely defined. SIRT1 may negatively modulate lipogenesis and liver triglyceride accumulation, involving AMP-activated protein kinase (AMPK) activation. In streptozotocin-diabetic rats, we hypothesized that insulin negatively modulates liver SIRT1 and activates AMPK-inhibited lipogenic mediators leading to triglyceride accumulation. The impact of insulin deprivation (INS-) and replacement (INS+) on liver inflammation and mitochondrial oxidative capacity (also potentially regulating triglyceride deposition) was also measured.
Streptozotocin-diabetic rats under chronic (8-week) INS- and INS+.
Compared to INS- (P < 0.05), INS+ had low liver SIRT1 with low AMPK activating phosphorylation, low inactivating phosphorylation of its lipogenic target acetyl-CoA carboxylase and high tissue triglycerides. INS- (P < 0.05 vs Control) had liver inflammation and high mitochondrial oxidative capacity, but neither was modulated by INS+. Pair-feeding showed no influence of spontaneous overeating on insulin-induced changes.
Insulin replacement downregulates SIRT1 and AMPK activation in vivo in streptozotocin-diabetic rat liver, likely contributing to insulin-induced liver triglyceride accumulation. Under the current experimental conditions, insulin-deprived diabetes is associated with liver inflammation and high mitochondrial oxidative capacity, that are not affected by insulin replacement and are therefore unlikely to contribute to tissue triglyceride changes in this model.
Clinical nutrition (Edinburgh, Scotland) 11/2010; 30(3):384-90. · 3.27 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Physical inactivity is associated with insulin resistance and decreased high-density lipoprotein (HDL) cholesterol. Cholesteryl ester transfer protein (CETP) is involved in cholesterol metabolism, being responsible for the transfer of cholesteryl esters from HDL to very low- and low-density lipoproteins.
We hypothesized that physical inactivity could decrease HDL cholesterol through changes in CETP availability.
Twenty-four healthy, male volunteers (aged 23.1 +/- 0.5 yr) were investigated in eucaloric conditions before and at the end of 35 d of experimental bed rest.
Changes in body composition were monitored by bioimpedance throughout the study. Before and at the end of the experimental period, plasma insulin and glucose and plasma lipid pattern as well as CETP concentrations were determined.
Our results demonstrated that during bed rest, fat mass did not change significantly, whereas fat-free mass decreased by 3.9 +/- 0.4% (P < 0.01). The homeostatic model assessment index of insulin resistance significantly (P < 0.001) increased by 47 +/- 11% after bed rest. Bed rest decreased HDL cholesterol by 12 +/- 3% (P < 0.05), increased triglycerides by 51 +/- 10% (P < 0.05), whereas it did not change significantly low-density lipoprotein cholesterol. Plasma CETP concentration increased after bed rest by 27 +/- 9% (P < 0.01). Bed rest-induced changes in CETP concentrations inversely correlated with changes in the ratio between HDL and non-HDL cholesterol (n = 24; R = -0.43; P < 0.05).
Physical inactivity decreases HDL cholesterol, at least in part, through CETP up-regulation.
The Journal of clinical endocrinology and metabolism 03/2010; 95(5):2508-12. · 6.50 Impact Factor
-
Laura Calabresi,
Damiano Baldassarre,
Samuela Castelnuovo,
Paola Conca,
Letizia Bocchi,
Chiara Candini,
Beatrice Frigerio,
Mauro Amato,
Cesare R Sirtori,
Paola Alessandrini,
Marcello Arca,
Giuliano Boscutti, Luigi Cattin,
Loreto Gesualdo,
Tiziana Sampietro,
Gaetano Vaudo,
Fabrizio Veglia,
Sebastiano Calandra,
Guido Franceschini
[show abstract]
[hide abstract]
ABSTRACT: Mutations in the LCAT gene cause lecithin:cholesterol acyltransferase (LCAT) deficiency, a very rare metabolic disorder with 2 hypoalphalipoproteinemia syndromes: classic familial LCAT deficiency (Online Mendelian Inheritance in Man No. 245900), characterized by complete lack of enzyme activity, and fish-eye disease (Online Mendelian Inheritance in Man No. 136120), with a partially defective enzyme. Theoretically, hypoalphalipoproteinemia cases with LCAT deficiency should be at increased cardiovascular risk because of high-density lipoprotein deficiency and defective reverse cholesterol transport.
The extent of preclinical atherosclerosis was assessed in 40 carriers of LCAT gene mutations from 13 Italian families and 80 healthy controls by measuring carotid intima-media thickness (IMT). The average and maximum IMT values in the carriers were 0.07 and 0.21 mm smaller than in controls (P=0.0003 and P=0.0027), respectively. Moreover, the inheritance of a mutated LCAT genotype had a remarkable gene-dose-dependent effect in reducing carotid IMT (P=0.0003 for average IMT; P=0.001 for maximum IMT). Finally, no significant difference in carotid IMT was found between carriers of LCAT gene mutations that cause total or partial LCAT deficiency (ie, familial LCAT deficiency or fish-eye disease).
Genetically determined low LCAT activity in Italian families is not associated with enhanced preclinical atherosclerosis despite low high-density lipoprotein cholesterol levels. This finding challenges the notion that LCAT is required for effective atheroprotection and suggests that elevating LCAT expression or activity is not a promising therapeutic strategy to reduce cardiovascular risk.
Circulation 09/2009; 120(7):628-35. · 14.74 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Metabolic syndrome is characterized by increased cardiovascular risk. Pentraxin 3 (PTX3), an acute phase protein, is involved in atherosclerosis. No information is available on PTX3 plasma concentrations in metabolic syndrome and on its associations with metabolic alterations and subclinical atherosclerosis. The aim of this study was to assess PTX3 plasma levels in metabolic syndrome patients compared to control subjects and their potential associations with anthropometric and clinical components of the syndrome as well as with carotid artery intima-media thickness (cIMT), a marker of subclinical atherosclerosis. Plasma was obtained from metabolic syndrome patients (NCEP-ATP III criteria n = 41, 20 M/21F) and by age-matched control subjects (n = 32, 16 M/16F). PTX3 was measured using sandwich ELISA and cIMT with ultrasound. Compared to those of the control subjects, plasma levels of PTX3 were higher (? * 100%, P = 0.0009) in metabolic syndrome patients. In univariate analysis, plasma PTX3 was negatively (P = 0.005) associated with high-density lipoprotein (HDL) cholesterol and positively (P = 0.046) with plasma triglycerides and with cIMT (P = 0.045) in the patients (n = 41). In multivariate analysis the direct association between PTX3 and cIMT was no longer significant after correction for HDL. None of these associations were detected in the control patients. These data demonstrate that PTX3, a novel marker of vascular disease, is higher in patients with metabolic syndrome associated with subclinical atherosclerosis. In addition, PTX3 is significantly independently correlated with low HDL cholesterol, but not with cIMT, suggesting a novel association between PTX3 and atherogenic lipid profile.
Clinical and Experimental Medicine 03/2009; 9(3):243-8. · 1.58 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the relationship between plasma HDL at admission and the extent of the inflammatory response during an ST-elevation myocardial infarction (STEMI), and to analyse structural HDL changes during STEMI as related to the extent of inflammation.
CRP and IL-6 were monitored for 96h in 45 patients with STEMI. Plasma apoA-II and LpA-I:A-II levels at admission, but not HDL cholesterol or other HDL-related biomarkers, were associated with the extent of the inflammatory response during STEMI, as indicated by the positive correlations with CRP AUC (apoA-II: F=7.44, p=0.009; LpA-I:A-II: F=14.29, p<0.001), and IL-6 AUC (apoA-II: F=6.98, p=0.012; LpA-I:A-II: F=6.67, p=0.013). By multivariate analysis the plasma LpA-I:A-II level at admission was a powerful independent predictor of the inflammatory response, evaluated either as CRP AUC (F=22.30, p<0.001), or IL-6 AUC (F=6.92, p=0.012). During STEMI, the plasma concentration of LpA-I:A-II, but not LpA-I particles decreased, HDL became larger and progressively enriched in serum amyloid A; these changes occurred only in patients with a significant inflammatory response.
An elevated plasma concentration of LpA-I:A-II particles was an independent predictor of a more severe inflammatory response in patients with STEMI.
Atherosclerosis 04/2008; 202(1):304-11. · 3.79 Impact Factor
-
Michela Zanetti,
Alessia Stocca,
Barbara Dapas,
Rossella Farra,
Laura Uxa,
Alessandra Bosutti,
Rocco Barazzoni,
Fleur Bossi,
Carlo Giansante,
Francesco Tedesco, Luigi Cattin,
Gianfranco Guarnieri,
Gabriele Grassi
[show abstract]
[hide abstract]
ABSTRACT: Fenofibrate has beneficial effects on the progression and clinical emergence of atherosclerosis in normoglycemic and in diabetic patients. Given the involvement of endothelium in these processes, we speculated that fenofibrate may influence endothelial cell apoptosis and proliferation, regulators of endothelium integrity. Fenofibrate effects on apoptosis and proliferation were studied in human umbilical vein endothelial cells under normal (5.5 mmol/l, NG) and high (22 mmol/l, HG) glucose with or without fenofibrate (50 micromol/l). Apoptosis was evaluated by annexin V, by poly(ADP-ribose) polymerase protein cleavage, and cyclooxygenase-2 (COX-2), Bax/Bcl-2, and p53 protein levels; proliferation was assessed by determining cell cycle phase distribution and the amounts of the cell cycle regulators E2F1, cyclin D1, E1, and A and the levels of the hyper-phosphorylated form of the retinoblastoma protein (ppRb). HG resulted in increased (p<0.05) apoptosis rate associated with COX-2 protein overexpression, without modification of Bax/Bcl2 ratio and p53 levels. Fenofibrate decreased apoptosis and normalized increased COX-2 expression in HG (p<0.05). Both in HG and NG, fenofibrate dramatically reduced cell proliferation (p<0.05) through a G1/G0 block mediated by the reduction in ppRb and the decrease in E2F1, cyclin E1, A, and D1 protein expression, with a mechanism that, for cyclin E1, occurred at the posttranscriptional level. In conclusion, our data show that fenofibrate reduces apoptosis caused by HG but severely interferes with endothelial cell proliferation both in NG and HG. The resulting effect may influence endothelium integrity in vivo and may impact the outcome of acute complications of atherosclerosis in diabetes.
Journal of Molecular Medicine 02/2008; 86(2):185-95. · 4.67 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Primary hypobetalipoproteinemia (HBL) includes a group of genetic disorders: abetalipoproteinemia (ABL) and chylomicron retention disease (CRD), with a recessive transmission, and familial hypobetalipoproteinemia (FHBL) with a co-dominant transmission. ABL and CRD are rare disorders due to mutations in the MTP and SARA2 genes, respectively. Heterozygous FHBL is much more frequent. FHBL subjects often have fatty liver and, less frequently, intestinal fat malabsorption. FHBL may be linked or not to the APOB gene. Most mutations in APOB gene cause the formation of truncated forms of apoB which may or may be not secreted into the plasma. Truncated apoBs with a size below that of apoB-30 are not detectable in plasma; they are more frequent in patients with the most severe phenotype. Only a single amino acid substitution (R463W) has been reported as the cause of FHBL. Approximately 50% of FHBL subjects are carriers of pathogenic mutations in APOB gene; therefore, a large proportion of FHBL subjects have no apoB gene mutations or are carriers of rare amino acid substitutions in apoB with unknown effect. In some kindred FHBL is linked to a locus on chromosome 3 (3p21) but the candidate gene is unknown. Recently a FHBL plasma lipid phenotype was observed in carriers of mutations of the PCSK9 gene causing loss of function of the encoded protein, a proprotein convertase which regulates LDL-receptor number in the liver. Inactivation of this enzyme is associated with an increased LDL uptake and hypobetalipoproteinemia. HBL carriers of PCSK9 mutations do not develop fatty liver disease.
Atherosclerosis 01/2008; 195(2):e19-27. · 3.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ghrelin administration can induce fat weight gain and hyperglycemia (potentially through ghrelin-induced hepatic glucose production), but plasma ghrelin is positively associated with whole-body insulin sensitivity (mainly reflecting muscle insulin action) being increased in lean individuals or after diet-induced weight loss and reduced in obesity or after diet-induced weight gain. To investigate potential mechanisms, we measured in vivo effects of sustained ghrelin administration at a non-orexigenic dose on skeletal muscle and liver insulin signaling at the AKT level and adipokine expression changes.
Young-adult male rats received 4-day, twice daily subcutaneous ghrelin (200 mug/injection) or saline. We measured skeletal muscle (mixed, gastrocnemius; oxidative, soleus) and liver protein levels of activated [phosphorylated (P)] and total (T) AKT and glycogen synthase kinase (GSK; reflecting AKT-dependent GSK inactivation) and epididymal adipose tissue adipokine mRNA.
Ghrelin increased body weight (+1.4%) and blood glucose (both p < 0.05 vs. saline) but not food intake, plasma insulin, or free fatty acids. Ghrelin, however, enhanced P/T/AKT and P/T/GSK ratios and glucose transporter-4 mRNA in soleus (p < 0.05), but not in gastrocnemius, muscle. In contrast, ghrelin reduced hepatic P/T-AKT and P/T-GSK. No alterations occurred in adiponectin, leptin, or resistin transcripts or plasma adiponectin.
Despite moderate weight gain and in the absence of insulin-free fatty acid changes, sustained ghrelin administration enhanced oxidative muscle AKT activation. Reduced liver AKT signaling could potentially contribute to concomitant blood glucose increments. These findings support ghrelin as a novel tissue-specific modulator of lean tissue AKT signaling with insulin-sensitizing effects in skeletal muscle but not in liver in vivo.
Obesity 12/2007; 15(11):2614-23. · 4.28 Impact Factor
-
Rocco Barazzoni,
Michela Zanetti,
Clara Ferreira,
Pierandrea Vinci,
Alessia Pirulli,
Mariapia Mucci,
Franca Dore,
Maurizio Fonda,
Beniamino Ciocchi, Luigi Cattin,
Gianfranco Guarnieri
[show abstract]
[hide abstract]
ABSTRACT: Metabolic syndrome shows clustered metabolic abnormalities with major roles for insulin resistance and obesity. Ghrelin is a gastric hormone whose total plasma concentration (T-Ghr) is associated positively with insulin sensitivity and is reduced in obesity. Ghrelin circulates in acylated (A-Ghr) and desacylated (D-Ghr) forms, but their potential differential associations with insulin resistance and whether they are differentially altered in obesity remain undefined.
Our objective was to determine potential differential associations of ghrelin forms with insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] and the impact of obesity on their plasma concentrations in metabolic syndrome.
This is a cross-sectional study.
The study was performed in a metabolic outpatient unit.
Patients with metabolic syndrome (National Cholesterol Education Program-Adult Treatment Panel III; n = 45, 23 males/22 females) were included in the study.
The main study outcomes were metabolic syndrome criteria, HOMA-IR, and ghrelin forms.
Plasma insulin and HOMA-IR were associated negatively with T-Ghr and D-Ghr but positively with A-Ghr and acylated to desacylated ghrelin (A/D-Ghr) ratio (n = 45; P < 0.05). Compared with nonobese [body mass index (BMI) < 27.5 kg/m(2); n = 12, six males/six females], obese metabolic syndrome patients (BMI > 27.5 kg/m(2); n = 33) had lower T-Ghr and D-Ghr but comparable A-Ghr and higher A/D-Ghr ratio (P < 0.05). BMI and waist circumference (WC) were positively related with HOMA-IR (n = 45; P < 0.05). However, opposite associations between A/D-Ghr ratio and HOMA-IR remained significant after adjustment for sex and BMI (or WC). Additional obese individuals without metabolic syndrome (n = 10: age-, sex-, BMI-, and WC-matched to obese metabolic syndrome patients) had lower T-Ghr but higher A-Ghr (P < 0.05) compared with age-, sex-matched healthy nonobese counterparts (n = 15). T-Ghr and A-Ghr were comparable in obese with or without metabolic syndrome.
Obesity could alter circulating ghrelin profile, and relative A-Ghr excess could contribute to obesity-associated insulin resistance in metabolic syndrome.
Journal of Clinical Endocrinology & Metabolism 11/2007; 92(10):3935-40. · 6.50 Impact Factor
-
Diabetes Care 09/2005; 28(8):2028-30. · 8.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Antiatherogenic effects of nitric oxide (NO) are mediated by activation of soluble guanylate cyclase (sGC) and are impaired by diabetes in animals and humans. We investigated whether uncontrolled diabetes and insulin therapy effect expression and function of the main enzymes of the endothelial nitric oxide (eNOS)-sGC signaling pathway in vivo. Expression and function of eNOS, sGC and protein kinase G (PKG) were studied by Western blot analysis and vasorelaxation to NO-donor in thoracic aortas from control (CON) and streptozotocin (SZT)-induced diabetic rats during uncontrolled diabetes (DM) and insulin treatment (INS) for 8 weeks. Protein level of eNOS was increased (+300%, P < 0.05), while sGC (-50%) and PKG (-65%) proteins were reduced (P < 0.03) in aortas of DM. Insulin treatment normalized these defects resulting in eNOS, sGC and PKG aortic protein content comparable to control. In aortic rings, diethylamine NONOate (DEA-NONOate)-induced vasorelaxation was attenuated (P< or =0.05) in DM compared to control and returned to normal in INS. Thus, experimental diabetes decreases sGC and PKG expression and their NO-dependent activation in aorta despite overexpression of eNOS. These abnormalities are normalized by insulin treatment and improved metabolic control.
Atherosclerosis 08/2005; 181(1):69-73. · 3.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Elevation of plasma cholesterol and/or triglycerides, and the prevalence of small dense low density lipoproteins (LDL) particles remarkably increase the risk in patients with familial combined hyperlipidemia (FCHL). There are, at present, inconsistent data on the effects of different treatments on size and density of LDL particles in FCHL patients.
A multicenter, randomized, double-blind, double-dummy, parallel group study was designed to evaluate the effect of 3 months' treatment with atorvastatin (10mg/day) or pravastatin (20mg/day) on the lipid/lipoprotein profile and LDL size in a total of 86 FCHL patients. Both statins significantly lowered plasma total and LDL cholesterol, with a significantly higher hypocholesterolemic effect observed with atorvastatin (-26.8+/-11.1% and -35.9+/-11.1%, respectively) compared to pravastatin (-17.6+/-11.1% and -24.5+/-10.2%). The percent decrease in plasma triglycerides was highly variable, but more pronounced with atorvastatin (-19.8+/-29.2%) than with pravastatin (-5.3+/-48.6%). Opposite changes in LDL size were seen with the 2 treatments, with increased mean LDL particle diameter with atorvastatin, and decreased diameter with pravastatin, and significant between treatment difference in terms of percent modification vs baseline (+0.5+/-1.6% with atorvastatin vs -0.3+/-1.8% with pravastatin).
The present results support the evidence indicative of a greater hypocholesterolemic effect of atorvastatin compared to pravastatin, and in addition show a raising effect of atorvastatin on the size of LDL particles in FCHL patients.
Nutrition Metabolism and Cardiovascular Diseases 03/2005; 15(1):47-55. · 3.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Ghrelin is a gastric hormone increased during caloric restriction and fat depletion. A role of ghrelin in the regulation of lipid and energy metabolism is suggested by fat gain independent of changes in food intake during exogenous ghrelin administration in rodents. We investigated the potential effects of peripheral ghrelin administration (two times daily 200-micrograms [DOSAGE ERROR CORRECTED] sc injection for 4 days) on triglyceride content and mitochondrial and lipid metabolism gene expression in rat liver and muscles. Compared with vehicle, ghrelin increased body weight but not food intake and circulating insulin. In liver, ghrelin induced a lipogenic and glucogenic pattern of gene expression and increased triglyceride content while reducing activated (phosphorylated) stimulator of fatty acid oxidation, AMP-activated protein kinase (AMPK, all P < 0.05), with unchanged mitochondrial oxidative enzyme activities. In contrast, triglyceride content was reduced (P < 0.05) after ghrelin administration in mixed (gastrocnemius) and unchanged in oxidative (soleus) muscle. In mixed muscle, ghrelin increased (P < 0.05) mitochondrial oxidative enzyme activities independent of changes in expression of fat metabolism genes and phosphorylated AMPK. Expression of peroxisome proliferator-activated receptor-gamma, the activation of which reduces muscle fat content, was selectively increased in mixed muscle where it paralleled changes in oxidative capacities (P < 0.05). Thus ghrelin induces tissue-specific changes in mitochondrial and lipid metabolism gene expression and favors triglyceride deposition in liver over skeletal muscle. These novel effects of ghrelin in the regulation of lean tissue fat distribution and metabolism could contribute to metabolic adaptation to caloric restriction and loss of body fat.
AJP Endocrinology and Metabolism 01/2005; 288(1):E228-35. · 4.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Insulin is a major post-prandial muscle-anabolic hormone. A substantial loss of skeletal muscle mass occurs in insulin-deprived diabetes and is reversed by insulin treatment. Myostatin is a negative regulator of muscle mass upregulated in several chronic catabolic conditions. Whether myostatin expression is altered in insulin-deprived diabetes is unknown. In spite of opposite effects on muscle mass the potential role of basal circulating insulin in the regulation of myostatin expression is also undetermined.
We measured (Northern Blot) myostatin transcript levels in muscle groups with different fiber composition in streptozotocin-diabetic male rats receiving one of the following treatments for eight weeks: (1) control (C); (2) diabetes without treatment (DM); (3) diabetes with once-daily slow-acting insulin treatment (INS).
INS normalized plasma insulin and prevented weight reduction observed in DM. In fast-twitch gastrocnemius muscle myostatin transcript levels were unchanged (P>0.4) in both DM and INS compared to C. Myostatin transcripts were not measurable in any group in slow-twitch soleus muscle.
Muscle-specific myostatin expression is not increased under catabolic conditions in insulin-deprived diabetes. Insulin treatment also does not change myostatin transcript levels. The data provide the first assessment of potential interplay between insulin and myostatin and they do not support a major role of circulating insulin in the in vivo regulation of myostatin gene expression. A role of myostatin in muscle catabolism in chronic insulin-deprived diabetes is also not indicated by the current results.
Clinical Nutrition 12/2004; 23(6):1413-7. · 3.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The lack in control of insulin release combined with an inadequate carbohydrate (CHO) ingestion accounts for the occurrence of frequent metabolic unbalances during exercise in type 1 diabetic patients. The aim of the study was to quantify, in these patients, the CHO requirement to prevent hypoglycemia during moderate exercise performed at different time intervals after morning subcutaneous insulin injection. Twelve type 1 diabetic patients and 12 well-matched healthy subjects cycled 4 times for 1 hour at a constant workload. The rate of glucose oxidation was calculated continuously by indirect calorimetry throughout the exercise, while blood parameters were assessed periodically and orally given CHO were checked. CHO needed by the patients to prevent hypoglycemia decreased as the time elapsed from insulin administration increased, amounting to 0.63 +/- 0.30, 0.44 +/- 0.32, 0.28 +/- 0.24, and 0.14 +/- 0.18 g/kg after 1, 2.5, 4, and 5.5 hours, respectively. Total glucose requirement during moderate exercise (sum of alimentary and extracellular source) was correlated (r = 0.739, P <.001) to plasma insulin concentration, but not with fitness level. Time elapsed from last insulin dose is not a factor influencing the risk of hypoglycemia during exercise when a proportional, appropriate amount of CHO is ingested.
Metabolism 09/2004; 53(9):1126-30. · 2.66 Impact Factor
-
Livia Pisciotta,
Ian Hamilton-Craig,
Patrizia Tarugi,
Antonella Bellocchio,
Tommaso Fasano,
Paola Alessandrini,
Gabriele Bittolo Bon,
Donatella Siepi,
Elmo Mannarino, Luigi Cattin,
Maurizio Averna,
Angelo Balassare Cefalù,
Alfredo Cantafora,
Sebastiano Calandra,
Stefano Bertolini
[show abstract]
[hide abstract]
ABSTRACT: Mutations in ABCA1 have been shown to be the cause of Tangier disease (TD) and some forms of familial hypoalphalipoproteinemia (HA), two genetic disorders characterized by low plasma HDL levels. Here we report six subjects with low HDL, carrying seven ABCA1 mutations, six of which are previously unreported. Two mutations (R557X and H160FsX173) were predicted to generate short truncated proteins; two mutations (E284K and Y482C) were located in the first extracellular loop and two (R1901S and Q2196H) in the C-terminal cytoplasmic domain of ABCA1. Two subjects found to be compound heterozygotes for ABCA1 mutations did not have overt clinical manifestations of TD. Three subjects, all with premature coronary artery disease (pCAD), had a combination of genetic defects. Besides being heterozygotes for ABCA1 mutations, two of them were also carriers of the R3500Q substitution in apolipoprotein B and the third was a carrier of N291S substitution in lipoprotein lipase. By extending family studies we identified 17 heterozygotes for ABCA1 mutations. Plasma HDL-C and Apo A-I values in these subjects were 38.3 and 36.9% lower than in unaffected family members and similar to the values found in heterozygotes for Apo A-I gene mutations which prevent Apo A-I synthesis. This survey underlines the allelic heterogeneity of ABCA1 mutations and suggests that: (i) TD subjects, if asymptomatic, may be overlooked and (ii) there may be a selection bias in genotyping towards carriers of ABCA1 mutations who have pCAD possibly related to a combination of genetic and environmental cardiovascular risk factors.
Atherosclerosis 03/2004; 172(2):309-20. · 3.79 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Small LDL are associated with risk of coronary heart disease. Gradient gel electrophoresis for LDL separation is not a simple method and high-quality non-denaturing gradient gels are lacking.
In this paper, we describe a method for the preparation of a polyacrylamide gel system that consists of an upper linear gradient gel (1.8-10%) and a lower homogeneous gel (16%) for the determination of LDL size.
The linear gradient is highly reproducible. Intra-inter gel coefficients of variation for LDL particle size are lower than 0.6%.
Effective LDL size measurement from pre-stained serum samples is possible in a stable gel.
Clinica Chimica Acta 01/2004; 338(1-2):73-8. · 2.54 Impact Factor
