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International audience; Cholesterol esterification proteins Sterol-O acyltransferases (SOAT) 1 and 2 are emerging prognostic markers in many cancers. These enzymes utilise fatty acids conjugated to coenzyme A to esterify cholesterol. Cholesterol esterification is tightly regulated and enables formation of lipid droplets that act as storage organelles for lipid soluble vitamins and minerals, and as cholesterol reservoirs. In cancer, this provides rapid access to cholesterol to maintain continual synthesis of the plasma membrane. In this systematic review and meta-analysis, we summarise the current depth of understanding of the role of this metabolic pathway in pan-cancer development. A systematic search of PubMed, Scopus, Web of Science, and Cochrane Library for preclinical studies identified eight studies where cholesteryl ester concentrations were compared between tumour and adjacent-normal tissue, and 24 studies where cholesterol esterification was blocked by pharmacological or genetic approaches. Tumour tissue had a significantly greater concentration of cholesteryl esters than non-tumour tissue (p < 0.0001). Pharmacological or genetic inhibition of SOAT was associated with significantly smaller tumours of all types (p ≤ 0.002). SOAT inhibition increased tumour apoptosis (p = 0.007), CD8 + lymphocyte infiltration and cytotoxicity (p ≤ 0.05), and reduced proliferation (p = 0.0003) and metastasis (p < 0.0001). Significant risk of publication bias was found and may have contributed to a 32% overestimation of the meta-analysed effect size. Avasimibe, the most frequently used SOAT inhibitor, was effective at doses equivalent to those previously reported to be safe and tolerable in humans. This work indicates that SOAT inhibition should be explored in clinical trials as an adjunct to existing anti-neoplastic agents.

Introduction. Inflammation is associated with obesity condition and plays a pivotal role in the onset and progression of many chronic diseases. Among several nutraceutical foods, hazelnuts (Corylus avellana L.) are considered an excellent anti-inflammatory and hypolipidemic food being the second richest source of monounsaturated fatty acids among nuts and because they are rich in vitamins, minerals, and phenolic compounds. Materials and Methods. A prospective pilot clinical trial on 24 healthy volunteers who consumed daily, as a snack, 40 g of hazelnuts (261.99 kcal/1096.17 kJ) for six weeks was conducted. Anthropometric measurements, body composition analysis, and nutrigenomic analysis on 12 anti-inflammatory and antioxidant genes were evaluated at baseline (T0) and after hazelnut intervention (T1). Results. No significant changes were detected on body composition analysis after hazelnut consumption. Conversely, significant upregulation was detected for SOD1 (2−ΔΔCt=2.42), CAT (2−ΔΔCt=2.41), MIF (2−ΔΔCt=4.12), PPARγ (2−ΔΔCt=5.89), VDR (2−ΔΔCt=3.61), MTHFR (2−ΔΔCt=2.40), and ACE (2−ΔΔCt=2.16) at the end of the study. Conclusions. According to emerging evidences, hazelnut consumption does not lead to weight gain probably due to the improvement of the body’s antioxidant capacity by the upregulation of genes implied in oxidant reactions and inflammation.

Interleukin-1β is one of pro-inflammatory responses and plays an important role in cell proliferation, differentiation, and apoptosis . The gene of this cytokine is highly polymorphic, one of which is located on 5´flanking region at position −511 (rs16944, A-511 G). This allele encodes IL-1β protein with less activity in comparison with wild type. In this research, 40 subjects of professional athletes in futsal and volleyball fields have been studied in their anthropometric and physiological indexes and also IL-1β genetic polymorphisms. Our results show that in subjects carrying IL-1β A (−) SNP or wild type allele, the weight, body fat and some other physiological indexes have been increased. This might have relation with elevated plasma level of leptin which is conducted by IL-1β A (−) allele. These findings suggest a remarkable relation between genetic polymorphisms of IL-1β gene and physical potential of athletes.

Background The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far. Methods We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects. Results We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02). Conclusions MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT01890070

Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double-blinded, placebo-controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3-week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed. Oxidation biomarkers like thiol group (p=0.001), total antioxidant status (TAS) (p=0.001), superoxide dismutase 1 (SOD1) (2−ΔΔCt = 3.7), and plasma concentration of HT (2.83μg·mL−1) were significantly increased, while nitrite (p=0.001), nitrate (p=0.001), and malondialdehyde (MDA) (p=0.02) were drastically reduced after HTT. A significant reduction of body fat mass percentage (p=0.01), suprailiac skinfold (p=0.01), and weight (p=0.04; Δ% = −0.46%) was observed after HTT. This study shows that regular intake of 15 mg/day of HT changed body composition parameters and modulated the antioxidant profile and the expression of inflammation and oxidative stress-related genes. However, it is advisable to personalize HT doses in order to exert its health benefits in CVD prevention and protection of LDL-C particles from oxidative damage. This trial is registered with ClinicalTrials.govNCT01890070.