Oxidised Apolipoprotein Peptidome Characterises Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) encompasses a spectrum of histological conditions ranging from simple steatosis to fibrosing steatohepatitis, and is a risk factor for cardiovascular diseases (CVD). While oxidised apolipoproteins A and B have been linked to obesity and CVD, the association between other oxidised apolipoproteins and MASLD is yet to be established. To fill this gap, we characterised the circulating serum peptidome of patients with MASLD.

Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).

Steatotic liver disease (SLD) and Hepatocellular Carcinoma (HCC) are characterised by a substantial rewiring of lipid fluxes caused by systemic metabolic unbalances and/or disrupted intracellular metabolic pathways. SLD is a direct consequence of the interaction between genetic predisposition and a chronic positive energy balance affecting whole-body energy homeostasis and the function of metabolically-competent organs. In this review, we discuss how the impairment of the cross-talk between peripheral organs and the liver stalls glucose and lipid metabolism, leading to unbalances in hepatic lipid fluxes that promote hepatic fat accumulation.

Chronic inorganic nitrate supplementation does not improve metabolic health and worsens disease progression in mice with diet-induced obesity.

Inorganic nitrate (NO) has been proposed to be of therapeutic use as a dietary supplement in obesity and related conditions including the metabolic syndrome (MetS), type II diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD). Administration of NO to endothelial nitric oxide synthase-deficient mice reversed aspects of MetS; however, the impact of NO supplementation in diet-induced obesity is not well understood. Here we investigated the whole body metabolic phenotype and cardiac and hepatic metabolism in mice fed a high-fat, high-sucrose (HFHS) diet for up to 12 mo of age, supplemented with 1 mM NaNO (or NaCl) in their drinking water.

Cardiovascular health and cancer risk associated with plant based diets: An umbrella review.

Context: Cardiovascular diseases (CVDs) and cancer are the two main leading causes of death and disability worldwide. Suboptimal diet, poor in vegetables, fruits, legumes and whole grain, and rich in processed and red meat, refined grains, and added sugars, is a primary modifiable risk factor. Based on health, economic and ethical concerns, plant-based diets have progressively widespread worldwide.

The acetyltransferase Gcn5 exerts antagonistic pleiotropic effects on chronological ageing.

Compared to replicative lifespan, epigenetic regulation of chronological lifespan (CLS) is less well understood in yeast. Here, by screening all the viable mutants of histone acetyltransferase (HAT) and histone deacetylase (HDAC), we demonstrate that Gcn5, functioning in the HAT module of the SAGA/SLIK complex, exhibits an epistatic relationship with the HDAC Hda1 to control the expression of starvation-induced stress response and respiratory cell growth. Surprisingly, the mutants lose their colony-forming potential early in the stationary phase but display a longer maximum CLS than their WT counterparts, suggesting the contradictory roles of Gcn5 in lifespan regulation.

Non-alcoholic fatty liver disease is characterised by a reduced polyunsaturated fatty acid transport via free fatty acids and high-density lipoproteins (HDL).

Background And Objectives: Non-alcoholic fatty liver disease (NAFLD) develops due to impaired hepatic lipid fluxes and is a risk factor for chronic liver disease and atherosclerosis. Lipidomic studies consistently reported characteristic hepatic/VLDL "lipid signatures" in NAFLD; whole plasma traits are more debated. Surprisingly, the HDL lipid composition by mass spectrometry has not been characterised across the NAFLD spectrum, despite HDL being a possible source of hepatic lipids delivered from peripheral tissues alongside free fatty acids (FFA).

Dietary squalene supplementation decreases triglyceride species and modifies phospholipid lipidomic profile in the liver of a porcine model of non-alcoholic steatohepatitis.

Squalene is a key minor component of virgin olive oil, the main source of fat in the Mediterranean diet, and had shown to improve the liver metabolism in rabbits and mice. The present research was carried out to find out whether this effect was conserved in a porcine model of hepatic steatohepatitis and to search for the lipidomic changes involved. The current study revealed that a 0.

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome.

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated "omics" approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS ( controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of lipogenesis.

Transcriptional, epigenetic and metabolic signatures in cardiometabolic syndrome defined by extreme phenotypes.

Background: This work is aimed at improving the understanding of cardiometabolic syndrome pathophysiology and its relationship with thrombosis by generating a multi-omic disease signature.

Methods/results: We combined classic plasma biochemistry and plasma biomarkers with the transcriptional and epigenetic characterisation of cell types involved in thrombosis, obtained from two extreme phenotype groups (morbidly obese and lipodystrophy) and lean individuals to identify the molecular mechanisms at play, highlighting patterns of abnormal activation in innate immune phagocytic cells. Our analyses showed that extreme phenotype groups could be distinguished from lean individuals, and from each other, across all data layers.

Obesity-Related Insulin Resistance: The Central Role of Adipose Tissue Dysfunction.

Obesity is a key player in the onset and progression of insulin resistance (IR), a state by which insulin-sensitive cells fail to adequately respond to insulin action. IR is a reversible condition, but if untreated leads to type 2 diabetes alongside increasing cardiovascular risk. The link between obesity and IR has been widely investigated; however, some aspects are still not fully characterized.

Adipose tissue insulin resistance and lipidome alterations as the characterizing factors of non-alcoholic steatohepatitis.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death.

Methods: In this narrative review, we have discussed the current knowledge in the pathophysiology of fatty liver disease, including both metabolic and non-metabolic factors, insulin resistance, mitochondrial function, as well as the markers of liver damage, giving attention to the alterations in lipid metabolism and production of lipotoxic lipids.

Lipid Remodeling in Hepatocyte Proliferation and Hepatocellular Carcinoma.

Background And Aims: Hepatocytes undergo profound metabolic rewiring when primed to proliferate during compensatory regeneration and in hepatocellular carcinoma (HCC). However, the metabolic control of these processes is not fully understood. In order to capture the metabolic signature of proliferating hepatocytes, we applied state-of-the-art systems biology approaches to models of liver regeneration, pharmacologically and genetically activated cell proliferation, and HCC.

Sarcopenic obesity and insulin resistance: Application of novel body composition models.

Objectives: Sarcopenic obesity (SO) is characterized by the co-occurrence of high adiposity (HA) and low muscle mass (LM) and has been associated with an increased risk for cardiometabolic diseases. The aim of this study was to investigate the association between markers of insulin sensitivity and SO defined by three novel body composition models: body composition phenotypes; truncal fat mass to appendicular skeletal mass (TrFM/ASM) ratio load capacity; and fat mass to fat-free mass (FM/FFM) ratio load capacity.

Methods: The study included 314 participants 18 to 65 y of age.

The association of dietary patterns and carotid intima-media thickness: A synthesis of current evidence.

Aims: Dietary pattern (DP) analysis has emerged as a holistic method to understand the effects of food intake on health outcomes. Though dietary intake has been associated with cardiovascular disease, the association of DPs and carotid intima-media thickness (CIMT), a robust early marker of cardiovascular disease progression has not been comprehensively investigated. This study systematically explores the association of a posteriori and a priori DPs and CIMT.

Deletion of Stearoyl-CoA Desaturase-1 From the Intestinal Epithelium Promotes Inflammation and Tumorigenesis, Reversed by Dietary Oleate.

Background & Aims: The enzyme stearoyl-coenzyme A desaturase 1 (SCD or SCD1) produces monounsaturated fatty acids by introducing double bonds into saturated bonds between carbons 9 and 10, with oleic acid as the main product. SCD1 is present in the intestinal epithelium, and fatty acids regulate cell proliferation, so we investigated the effects of SCD1-induced production of oleic acid in enterocytes in mice.

Methods: We generated mice with disruption of Scd1 selectively in the intestinal epithelium (iScd1 mice) on a C57BL/6 background; iScd1 mice were used as controls.

Does a Mediterranean-type dietary pattern exert a cardio-protective effect outside the Mediterranean region? A review of current evidence.

Current evidence suggests a beneficial effect of the Mediterranean diet (MD) on human health. This has led to a rise in studies investigating the role of the MD in cardiovascular disease (CVD) prevention outside the region of its origin. We aimed to outline the evolving understanding of the MD and to provide an overview of adherence to MD in non-Mediterranean countries and the modulatory effects of MD on CVD biomarkers.

Association between ratio indexes of body composition phenotypes and metabolic risk in Italian adults.

The ratio between fat mass (FM) and fat-free mass (FFM) has been used to discriminate individual differences in body composition and improve prediction of metabolic risk. Here, we evaluated whether the use of a visceral adipose tissue-to-fat-free mass index (VAT:FFMI) ratio was a better predictor of metabolic risk than a fat mass index to fat-free mass index (FMI:FFMI) ratio. This is a cross-sectional study including 3441 adult participants (age range 18-81; men/women: 977/2464).