Giovannangelo Oriani

Antioxidants as antidepressants: fact or fiction?

Depression is a medical condition with a complex biological pattern of aetiology, involving genetic and epigenetic factors, along with different environmental stressors. Recent evidence suggests that oxidative stress pro-cesses might play a relevant role in the pathogenic mechanism(s) underlying many major psychiatric disorders, including depression.Reactive oxygen and nitrogen species have been shown to modulate levels and activity of noradrenaline (norepinephrine), serotonin, dopamine and glutamate, the principal neurotransmitters involved in the neurobiology of depression. Major depression has been associated with lowered concentrations of several endogenous antioxidant compounds, such as vitamin E, zinc and coenzyme Q10, or enzymes, such as glutathione peroxidase, and with an impairment of the total antioxidant status. These observations introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds.The present review focuses on the possible role of oxidative stress processes in the pathogenesis of depression. The therapeutic potential of antioxidant compounds as a co-adjuvant treatment to conventional antidepressants is discussed. For instance, N-acetyl-cysteine has been shown to have a signif-icant benefit on depressive symptoms in a randomized placebo-controlled trial. Additionally, curcumin, the yellow pigment of curry, has been shown to strongly interfere with neuronal redox homeostasis in the CNS and to possess antidepressant activity in various animal models of depression, also thanks to its ability to inhibit monoamine oxidases. There is an urgent need to develop better tolerated and more effective treatments for depressive disorders and several antioxidant treatments appear promising and deserve further study.

The Major Green Tea Polyphenol, (-)-Epigallocatechin-3-Gallate, Induces Heme Oxygenase in Rat Neurons and Acts as an Effective Neuroprotective Agent against Oxidative Stress

Background: Oxidative stress induced by hyperglycemia is a key factor in the pathogenesis of diabetic complications, such as neuropathy. Recently, green tea catechins have received much attention, as they can facilitate a number of antioxidative mechanisms and improve glycemic control. Objective: The aim of this study was to investigate the cytoprotective effects of (-)-epigallocatechin-3-gallate (EGCG) against oxidative stress damage in a cell line of rat neurons. The role of heme oxygenase 1 (HO-1) induction by EGCG and the transcriptional mechanisms involved were also evaluated. Methods: Immortalized rat neurons (H 19-7) were exposed to various concentrations of EGCG (10–200 µM). After treatments (6 or 24 hours), cells were harvested for the determination of heme oxygenase activity, mRNA levels, and protein expression. Nuclear levels of Nrf2, a transcriptional factor involved in HO-1 activation, were also measured. Neurons were pretreated for 12 hours with EGCG 50 µM or EGCG 50 µM + zinc protoporphyrin IX 10 µM and then exposed for 2 hours to 50 mµ/mL glucose-oxidase before cell viability was determined. Results: In cultured neurons, elevated expression of HO-1 mRNA and protein were detected after 6 hours of incubation with 25–100 µM EGCG, and its induction relates with the activation of Nrf2. Interestingly, pre-incubation (12 hours) with EGCG 50 µM resulted in an enhanced cellular resistance to glucose oxidase–mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of heme oxygenase activity. Conclusions: In this study, we demonstrated that EGCG, the major green tea catechin, induced HO-1 expression in cultured neurons, possibly by activation of the transcription factor Nrf2, and by this mechanism was able to protect against oxidative stress–induced cell death.

Adiponectin oligomerization state and adiponectin receptors airway expression in chronic obstructive pulmonary disease

Adiponectin (Acrp30) shows several beneficial properties and circulates as different oligomers. The role of Acrp30 in lung is not fully clear, but a link with chronic obstructive pulmonary disease (COPD) has been highlighted. In this study, we analyzed the anthropometrical and biochemical features and evaluated total Acrp30 levels of a COPD cohort without metabolic complications compared to healthy controls. In addition, being the oligomerization state critical for its biological activities, we characterized the pattern of Acrp30 circulating oligomers focusing on the high molecular weight (HMW) oligomers to verify whether it correlates to COPD. Finally, we investigated AdipoR1 and AdipoR2 expression in lung from COPD. Interestingly, we found for the first time that the oligomerization state of Acrp30 is altered in COPD; particularly, we observed that the higher levels of Acrp30 are associated with a significant and specific increase of HMW. In addition, we demonstrated the presence of AdipoRs with a lower expression of AdipoR2 compared to AdipoR1. In conclusion, we demonstrated that in COPD, the higher levels of Acrp30 are associated with the significantly increase of HMW representing the most biologically active forms. The important role of Acrp30 in pathophysiological conditions of lung is supported also by the modulation of AdipoRs with the down regulation of AdipoR2. The low expression of AdipoR2 could suggest a specific role of this receptor, mainly implicated in Acrp30 effects on inflammation and oxidative stress. Thus, total Acrp30, HMW and its receptors could be considered critical targets to improve diagnostic and therapeutic strategies for lung diseases.

Prediction of lean body mass from multifrequency segmental impedance: influence of adiposity.

Abstract The aim of the study was to determine the influence of adiposity on the relationship between bioelectrical impedance (BIA) measurements of body segments and estimation of body composition by dual-energy X-ray absorptiometry (DXA). Multiple frequencies of whole body and segmental impedances were measured in 68 normal-weight and obese subjects (46 women and 22 men), mean age 37.2±14.8 years (range, 18–69). Total and appendicular lean body mass (LBM) assessed by DXA correlated significantly with total and segmental impedance values adjusted for stature in both obese and normal-weight subjects. Best fitting equations for the prediction of appendicular LBM from segmental impedance measurements were derived for the arm and leg with and without the inclusion of adiposity (the percentage of body fat measured by DXA) in the regression models. Best prediction was obtained at low frequency for the arm and high frequency for the leg. Adiposity appears to significantly influence the prediction of leg LBM by BIA. These preliminary observations need further validation to provide an accurate assessment of appendicular LBM assessment by BIA.

Analysis of adiponectin gene and comparison of its expression in two different pig breeds.

Adiponectin, an adipokine secreted from adipose tissue (AT), exerts beneficial pleiotropic effects on obesity‐related metabolic diseases. We have analyzed the adiponectin gene (ACDC) and its expression in two genetically different breeds of pigs, lean type, large white (LW) and fat type, Casertana (CE). DNA, RNA, and protein extracts from 10 LW and 10 CE pigs were analyzed by sequence analysis, enzyme‐linked immunosorbent assay (ELISA), fast protein liquid chromatography, and northern and western blotting. Sequence analysis revealed an identity of 100% between the ACDC gene from the two breeds, but the expression of the adiponectin protein was higher in LW than in CE pigs. We identified sexual dimorphism of adiponectin in both breeds, namely a balanced distribution of the low isoforms (∼50 kDa), whereas the middle isoforms (∼75–150 kDa) were increased in sows. In conclusion, in this study, we demonstrate that adiponectin is produced and secreted differently in the two breeds of pig, namely adiponectin is more abundant in LW than in CE. Moreover, the visceral AT of LW expresses more adiponectin than the subcutaneous AT. This relationship is absent in CE. These observations provided the first evidence that adiponectin expression is correlated with the “fat” phenotype in pig.

Decreased concentration of adiponectin together with a selective reduction of its high molecular weight oligomers is involved in metabolic complications of myotonic dystrophy type 1

OBJECTIVE The hormone adiponectin exerts beneficial pleiotropic effects on biological and metabolic processes. Although a well-recognized insulin sensitizer, its characteristic has yet to be clearly defined. Myotonic dystrophy type 1 (DM1) is a rare genetic disorder that features muscle wasting and metabolic comorbidity, and patients have an increased risk of developing type 2 diabetes. We analyzed circulating levels of adiponectin and its oligomers to determine whether their expression correlates with metabolic alterations in DM1 patients. DESIGN AND METHODS We measured the anthropometric and biochemical features and three insulin resistance (IR) indices (homeostasis model assessment, quantitative insulin sensitivity check index, and McAuley) of 21 DM1 patients and of 82 age-, sex-, and weight-matched controls. In the blood samples of patients and controls, adiponectin levels were measured by ELISA, and its oligomers were characterized by using western blotting and gel filtration. The adiponectin gene was molecularly analyzed in patients. RESULTS DM1 patients had significantly higher body mass index, waist circumference, triglycerides (TGs), glucose, tumor necrosis factor α, and IR; conversely, they had significantly lower concentrations of total serum adiponectin with a selective, pronounced decrease of its high molecular weight (HMW) oligomers. There was a strong negative correlation between adiponectin and TGs in DM1 patients. CONCLUSIONS Our results endorse the hypothesis that decreased expression of adiponectin together with a selective reduction of its HMW oligomers contributes to the worsening of IR and its metabolic complications in DM1 patients. These findings suggest that adiponectin and HMW oligomers may serve as biomarkers and are promising therapeutic agents for IR and its consequences in DM1.

Resting metabolic rate in Italians : relation with body composition and anthropometric parameters

Abstract The objectives of this study were to obtain values for resting metabolic rate in Italians in relation to parameters of body composition, and to compare them to predicted values using the FAO/WHO/UNU equation. We performed a cross-sectional observational study of 131 healthy subjects (46 males and 85 females) at the Human Nutrition Unit, University Tor Vergata, Rome. Body composition was determined by dual energy X-ray absorptiometry (DXA) and resting metabolic rate was calculated using their Weir formula. Resting metabolic rate was 1865 ± 234 kcal/day in males and 1354 ± 154 kcal/day in females. These values decreased slightly with age. The relationships with weight and age were stronger than that with lean mass from DXA as independent variables in multiple regression analysis. Mean resting metabolic rates predicted with FAO/WHO/UNU and Harris-Benedict formula were not significantly different from measured values except for the Harris-Benedict value for females (p < 0.01). Individual differences between measured and predicted values were notably high. The measured values were higher than those reported in the literature. The prediction of resting metabolic rate is more accurate with simple anthropometric parameters than with fat-free mass obtained by DXA. The individual error in the predicted values can be so high that for individual use a measured value is preferred over an estimated value.

Adiponectin as Novel Regulator of Cell Proliferation in Human Glioblastoma

Adiponectin (Acrp30) is an adipocyte‐secreted hormone with pleiotropic metabolic effects, whose reduced levels were related to development and progression of several malignancies. We looked at the presence of Acrp30 receptors in human glioblastomas (GBM), hypothesizing a role for Acrp30 also in this untreatable cancer. Here we demonstrate that human GBM express Acrp30 receptors (AdipoR1 and AdipoR2), which are often co‐expressed in GBM samples (70% of the analyzed tumors). To investigate the effects of Acrp30 on GBM growth, we used human GBM cell lines U87‐MG and U251, expressing both AdipoR1 and AdipoR2 receptors. In these cells, Acrp30 treatment inhibits DNA synthesis and cell proliferation rate, inducing arrest in G1 phase of the cell cycle. These effects were correlated to a sustained activation of ERK1/2 and Akt kinases, upon Acrp30 treatment. Our results suggest that Acrp30 may represent a novel endogenous negative regulator of GBM cell proliferation, to be evaluated for the possible development of novel pharmacological approaches. J. Cell. Physiol. 229: 1444–1454, 2014.

Tissue-specific downregulation of the adiponectin "system": possible implications for fat accumulation tendency in the pig

Adiponectins beneficial effects are mediated by the AdipoR1 and AdipoR2 receptors (AdipoRs). The pig is a good model to study complex disorders such as obesity. We analyzed the expression of adiponectin, AdipoRs and some key molecules of energy metabolism (AMP-activated protein kinase α [AMPKα], p38 mitogen-activated protein kinase [p38 MAPK], and PPARα) in 2 pig breeds that displayed an opposite genetic behavior for energy metabolism: Casertana (CE), a fat-type animal, and Large White (LW), a lean-type animal. Muscle, liver, visceral and subcutaneous adipose tissues, and brain tissues were examined. The AdipoRs cDNA sequences were identical in the 2 breeds. AdipoRs mRNA expression, measured in all tissues, was significantly lower only in the 2 adipose tissues of CE pigs (P < 0.05). The muscle expression of AdipoRs, AMPKα, p38 MAPK, and PPARα was lower in CE than in LW animals (P < 0.01, P < 0.05, P < 0.01, P < 0.01, respectively). In liver, no molecule differed between breeds. The expression of both AdipoRs in visceral and subcutaneous adipose tissues was lower in CE pigs (P < 0.01). In brain, AdipoR1 and AMPKα expression was lower in CE pigs (P < 0.01), whereas AdipoR2 tended to be lower in CE than LW pigs (P = 0.05). In conclusion, our results suggest that tissue-specific downregulation of Adiponectin, AdipoRs, and of the key molecules of energy metabolism may be associated with the tendency of CE pigs to accumulate fat.

Nutritional evaluation of some processed catering foods

Five prepared catering dishes were analysed to evaluate the proximate composition and the fatty acids, vitamin E, thiamine and riboflavin content. The correspondent values were calculated from actually available food composition tables (two from Italy, one from the UK and one from the USA). When using more than one database to calculate the composition of a complex recipe the average values were similar to the analytical ones despite the wide range reported for some variables. However, there was no significant difference in the statistical analyses between the analytical values and databases, or among the databases themselves. Therefore if the composition of a specific recipe is required, analyses would be advisable, but the available databases are quite adequate if the evaluation is for groups of people, even allowing for the seasonal variability of ingredients.