Luca Vanella

Bio: Luca Vanella is an academic researcher from University of Catania. The author has contributed to research in topics: Heme oxygenase & Adiponectin. The author has an hindex of 38, co-authored 137 publications receiving 4058 citations. Previous affiliations of Luca Vanella include University of Brescia & New York Medical College.

Heme oxygenase-1 induction remodels adipose tissue and improves insulin sensitivity in obesity-induced diabetic rats.

Abstract: Obesity-associated inflammation causes insulin resistance. Obese adipose tissue displays hypertrophied adipocytes and increased expression of the cannabinoid-1 receptor. Cobalt protoporphyrin (CoPP) increases heme oxygenase-1 (HO-1) activity, increasing adiponectin and reducing inflammatory cytokines. We hypothesize that CoPP administration to Zucker diabetic fat (ZDF) rats would improve insulin sensitivity and remodel adipose tissue. Twelve-week-old Zucker lean and ZDF rats were divided into 4 groups: Zucker lean, Zucker lean-CoPP, ZDF, and ZDF-CoPP. Control groups received vehicle and treatment groups received CoPP (2 mg/kg body weight) once weekly for 6 weeks. Serum insulin levels and glucose response to insulin injection were measured. At 18 weeks of age, rats were euthanized, and aorta, kidney, and subcutaneous and visceral adipose tissues were harvested. HO-1 expression was measured by Western blot analysis and HO-1 activity by serum carbon monoxide content. Adipocyte size and cannabinoid-1 expression were measured. Adipose tissue volumes were determined using MRI. CoPP significantly increased HO-1 activity, phosphorylated AKT and phosphorylated AMP kinase, and serum adiponectin in ZDF rats. HO-1 induction improved hyperinsulinemia and insulin sensitivity in ZDF rats. Subcutaneous and visceral adipose tissue volumes were significantly decreased in ZDF rats. Adipocyte size and cannabinoid-1 expression were both significantly reduced in ZDF-CoPP rats in subcutaneous and visceral adipose tissues. This study demonstrates that HO-1 induction improves insulin sensitivity, downregulates the peripheral endocannabinoid system, reduces adipose tissue volume, and causes adipose tissue remodeling in a model of obesity-induced insulin resistance. These findings suggest HO-1 as a potential therapeutic target for obesity and its associated health risks.

Epoxyeicosatrienoic acid agonist rescues the metabolic syndrome phenotype of HO-2-null mice.

Abstract: Heme oxygenase (HO) and cytochrome P450 (P450)-derived epoxyeicosatrienoic acids (EETs) participate in vascular protection, and recent studies suggest these two systems are functionally linked. We examined the consequences of HO deficiency on P450-derived EETs with regard to body weight, adiposity, insulin resistance, blood pressure, and vascular function in HO-2-null mice. The HO-2-null mice were obese, displayed insulin resistance, and had high blood pressure. HO-2 deficiency was associated with decreases in cyp2c expression, EET levels, HO-1 expression, and HO activity and with an increase in superoxide production and an impairment in the relaxing response to acetylcholine. In addition, HO-2-null mice exhibited increases in serum levels of tumor necrosis factor (TNF)-α and macrophage chemoattractant protein (MCP)-1 and a decrease in serum adiponectin levels. Treatment of HO-2-null mice with a dual-activity EET agonist/soluble epoxide hydrolase inhibitor increased renal and vascular EET levels and HO-1 expression, lowered blood pressure, prevented body weight gain, increased insulin sensitivity, reduced subcutaneous and visceral fat, and decreased serum TNF-α and MCP-1, while increasing adiponectin and restoring the relaxing responses to acetylcholine. The decrease in cyp2c expression and EETs levels in HO-2-null mice underscores the importance of the HO system in the regulation of epoxygenase levels and suggests that protection against obesity-induced cardiovascular complications requires interplay between these two systems. A deficiency in one of these protective systems may contribute to the adverse manifestations associated with the clinical progression of the metabolic syndrome.

Adipocyte Heme Oxygenase-1 Induction Attenuates Metabolic Syndrome in Both Male and Female Obese Mice

Abstract: Increases in visceral fat are associated with increased inflammation, dyslipidemia, insulin resistance, glucose intolerance, and vascular dysfunction. We examined the effect of the potent heme oxygenase (HO)-1 inducer, cobalt protoporphyrin (CoPP), on regulation of adiposity and glucose levels in both female and male obese mice. Both lean and obese mice were administered CoPP intraperitoneally (3 mg/kg once per week) for 6 weeks. Serum levels of adiponectin, tumor necrosis factor α (TNFa), interleukin (IL)-1β and IL-6, and HO-1, PPARγ, pAKT, and pAMPK protein expression in adipocytes and vascular tissue were measured. While female obese mice continued to gain weight at a rate similar to controls, induction of HO-1 slowed the rate of weight gain in male obese mice. HO-1 induction led to lowered blood pressure levels in obese male and female mice similar to that of lean male and female mice. HO-1 induction also produced a significant decrease in the plasma levels of IL-6, TNFα, IL-1β, and fasting glucose of obese females compared to untreated female obese mice. HO-1 induction increased the number and decreased the size of adipocytes of obese animals. HO-1 induction increased adiponectin, pAKT, pAMPK, and PPARγ levels in adipocyte of obese animals. Induction of HO-1 in adipocytes was associated with an increase in adiponectin and a reduction in inflammatory cytokines. These findings offer the possibility of treating not only hypertension, but also other detrimental metabolic consequences of obesity including insulin resistance and dyslipidemia in obese populations by induction of HO-1 in adipocytes.

Antiproliferative effect of oleuropein in prostate cell lines

Abstract: Currently, there is increasing interest in the in vivo protective effects of natural antioxidants found in dietary plants against oxidative damage caused by free radical species. Oxidative stress has been invoked as a causative agent in cancer and epidemiological data suggest that the consumption of fruits and vegetables may be associated with a lower incidence of cancer. The fruit of the Olea europaea L. and olive oil contain hundreds of phytochemicals and its extracts have recently been shown to exhibit antioxidant properties, due to the action of oleuropein. In view of these considerations, in this study, we investigated the effects of oleuropein on LNCaP and DU145 prostate cancer cell lines and on BPH-1 non-malignant cells. Oleuropein reduces cell viability and induces thiol group modifications, γ-glutamylcysteine synthetase, reactive oxygen species, pAkt and heme oxygenase-1. Exposing cell cultures to oleuropein induces an antioxidant effect on BPH-1 cells and a pro-oxidant effect on cancer cells. Our results confirm the beneficial properties of olive oil and oleuropein, suggesting its possible use as an adjuvant agent in the treatment of prostatitis, in order to prevent the transformation of hypertrophic to cancerous cells.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

The therapeutic potential of carbon monoxide.

Abstract: Carbon monoxide (CO) is increasingly being accepted as a cytoprotective and homeostatic molecule with important signalling capabilities in physiological and pathophysiological situations. The endogenous production of CO occurs through the activity of constitutive (haem oxygenase 2) and inducible (haem oxygenase 1) haem oxygenases, enzymes that are responsible for the catabolism of haem. Through the generation of its products, which in addition to CO includes the bile pigments biliverdin, bilirubin and ferrous iron, the haem oxygenase 1 system also has an obligatory role in the regulation of the stress response and in cell adaptation to injury. This Review provides an overview of the physiology of CO, summarizes the effects of CO gas and CO-releasing molecules in preclinical animal models of cardiovascular disease, inflammatory disorders and organ transplantation, and discusses the development and therapeutic options for the exploitation of this simple gaseous molecule.

Anthocyanins: Natural Colorants with Health-Promoting Properties

Abstract: Anthocyanins are flavonoids in fruits and vegetables that render them vivid red to blue. To date, there have been more than 635 anthocyanins identified in nature, featuring six common aglycones and various types of glycosylations and acylations. Dietary consumption of anthocyanins is high compared to other flavonoids, owing to their wide distribution in plant materials. Based upon many cell-line studies, animal models, and human clinical trials, it has been suggested that anthocyanins possess anti-inflammatory and anti-carcinogenic activity, cardiovascular disease prevention, obesity control, and diabetes alleviation properties, all of which are more or less associated with their potent antioxidant property. Evidence suggests that absorption of anthocyanins occurs in the stomach and small intestine. Epithelial tissue uptake seems to be highly efficient, yet transportation into circulation, tissue distribution, and urine excretion are very limited. The bioactivity of bioavailable anthocyanins should be a f...