Metabolic reprogramming is critically involved in the development and progression of cancer. In particular, lipid metabolism has been investigated as a source of energy, micro-environmental adaptation, and cell signalling in neoplastic cells. However, the specific role of lipid metabolism dysregulation in hepatocellular carcinoma (HCC) has not been widely described yet. Alterations in fatty acid synthesis, β-oxidation, and cellular lipidic composition contribute to initiation and progression of HCC. The aim of this review is to elucidate the mechanisms by which lipid metabolism is involved in hepatocarcinogenesis and tumour adaptation to different conditions, focusing on the transcriptional aberrations with new insights in lipidomics and lipid zonation. This will help detect new putative therapeutic approaches in the second most frequent cause of cancer-related death.

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome and has become the major cause of chronic liver disease, especially in western countries. NAFLD encompasses a wide spectrum of hepatic histological alterations, from simple steatosis to steatohepatitis and cirrhosis with a potential development of hepatocellular carcinoma. Non-alcoholic steatohepatitis (NASH) is characterized by lobular inflammation and fibrosis. Several studies reported that insulin resistance, redox unbalance, inflammation, and lipid metabolism dysregulation are involved in NAFLD progression. However, the mechanisms beyond the evolution of simple steatosis to NASH are not clearly understood yet. Recent findings suggest that different oxidized products, such as lipids, cholesterol, aldehydes and other macromolecules could drive the inflammation onset. On the other hand, new evidence indicates innate and adaptive immunity activation as the driving force in establishing liver inflammation and fibrosis. In this review, we discuss how immunity, triggered by oxidative products and promoting in turn oxidative stress in a vicious cycle, fuels NAFLD progression. Furthermore, we explored the emerging importance of immune cell metabolism in determining inflammation, describing the potential application of trained immune discoveries in the NASH pathological context.

Idiopathic sudden sensorineural hearing loss (ISSHL) is a common otologic emergency whose cause is still unclear. The importance of blood lipids in the pathogenesis of ISSHL is widely reported in literature. In fact elevated levels of low density lipoprotein cholesterol (LDL), total cholesterol (TC) and apolipoprotein B (Apo-B) have been proposed as risk factors for this pathology. No correlation has been described between serum lipid parameters and the prognosis of ISSHL. Aim of the present study was to identify prognostic factors associated with hearing recovery in a group of patients affected by ISSHL. Ninety-four patients with the diagnosis of ISSHL hospitalized between March 2013 and October 2014 were included in this study. Patients’ blood sampling and hearing assessments were carried out. Patients were divided into two groups as “recovered” and “unrecovered”, according to their response to the treatment. We found a statistically significant higher level of total cholesterol in the unrecovered group compared to the recovered one (p = 0.03). None of the other routine laboratory parameters have shown a statistically significant difference between the patients successfully treated and patients with poor outcomes. Total cholesterol concentrations may be a prognostic factor for recovery in ISSHL and should be assessed together with routine tests in patients with this condition. The other routine laboratory parameters seem to have no effect on the development and prognosis of this pathology.

Although direct-acting antivirals are very effective and safe drugs, several authors have reported the alteration of lipid profile during and after anti-HCV therapy suggesting a potential impact on the risk of cardiovascular events. We performed a systematic review and meta-analysis of observational studies to investigate the magnitude and temporal trend of lipid profile changes in DAA treated patients. All selected studies included data on lipid profile before starting therapy and at least one follow-up assessment during or after antiviral treatment. We identified 14 studies (N = 1537 patients) after removing duplicates. Pooled data showed an increase in total cholesterol 4 weeks after starting therapy (+ 15.86 mg/dl; 95% CI + 9.68 to 22.05; p < 0.001) and 12 weeks after treatment completion (+ 17.05 mg/dl; 95% CI + 11.24 to 22.85; p < 0.001). LDL trend was similar to the total cholesterol change in overall analysis. A mean increase in HDL-cholesterol of 3.36 mg/dl (95% CI + 0.92 to 5.79; p = 0.07) was observed after 12 weeks of treatment, whereas at SVR24 HDL difference was + 4.34 mg/dl (95% CI + 1.40 to 7.28; p = 0.004).Triglycerides did not show significant changes during treatment and after treatment completion. DAAs induce mild lipid changes in chronic hepatitis C patients treated with DAAs, which may persist after treatment completion.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease globally, and represents a health care burden as treatment options are very scarce. The reason behind the NAFLD progression to non-alcoholic steatohepatitis (NASH) is not completely understood. Recently, the deficiency of micronutrients (e.g., vitamins, minerals, and other elements) has been suggested as crucial in NAFLD progression, such that recent studies reported the potential hepatic antioxidant properties of micronutrients supplementation. However, very little is known. Here we have explored the potential beneficial effects of dietary supplementation with FLINAX, a novel mixture of nutraceuticals (i.e., vitamin E, vitamin D3, olive dry-extract, cinnamon dry-extract and fish oil) in a NAFLD model characterized by oxidative stress and mitochondrial function impairment. Steatosis was firstly induced in Wistar rats by feeding with a high-fat/high-cholesterol diet for 4 weeks, and following this the rats were divided into two groups. One group (n = 8) was treated for 2 weeks with a normal chow-diet, while a second group (n = 8) was fed with a chow-diet supplemented with 2% FLINAX. Along with the entire experiment (6 weeks), a third group of rats was fed with a chow-diet only as control. Statistical analysis was performed with Student’s T test or one-way ANOVA followed by post-hoc Bonferroni test when appropriate. Steatosis, oxidative stress and mitochondrial respiratory chain (RC) complexes activity were analyzed in liver tissues. The dietary supplementation with FLINAX significantly improved hepatic steatosis and lipid accumulation compared to untreated rats. The mRNA and protein levels analysis showed that CPT1A and CPT2 were up-regulated by FLINAX, suggesting the enhancement of fatty acids oxidation (FAO). Important lipoperoxidation markers (i.e., HNE- and MDA-protein adducts) and the quantity of total mitochondrial oxidized proteins were significantly lower in FLINAX-treated rats. Intriguingly, FLINAX restored the mitochondrial function, stimulating the activity of mitochondrial RC complexes (i.e., I, II, III and ATP-synthase) and counteracting the peroxide production from pyruvate/malate (complex I) and succinate (complex II). Therefore, the supplementation with FLINAX reprogrammed the cellular energy homeostasis by restoring the efficiency of mitochondrial function, with a consequent improvement in steatosis.