Identification of a novel ANGPTL3 mutation splicing associeted to severe hypobetalipoproteinemia

Introduction. Primary hypobetalipoproteinemia (pHBL) is a monogenic heterogeneous condition inherited as a dominant or recessive trait characterized by total cholesterol (TC) and/or LDL cholesterol (LDL-C) and/or apolipoprotein B (APOB) levels below the 5th percentile of the reference population. Heterozygous APOB gene mutations are responsible for the majority of the dominant pHBL causing the familial hypobetalipoproteinemia (FHBL). Loss-of-function mutations in the PCSK9 gene also cause FHBL. Familial combined hypolipidemia is a recently discovered dyslipidemic phenotype characterized by low levels of TC, triglycerides (TG), LDL-C, and high-density lipoprotein cholesterol (HDL-C). The gen…

LA LIPIDOMICA DELLA NON ALCOHOLIC FATTY LIVER DISEASE: ANALISI DELLA CINETICA DELL’ACIDO PALMITICO MEDIANTE L’USO DI UN ISOTOPO STABILE IN UN MODELLO IN VITRO

LIPIDOMICS OF HUMAN SKIN FIBROBLASTS IN NEIMANN-PICK DISEASE TYPE C

Neimann-Pick Disease type C is a hereditary lysosomal storage disease due to mutations of the NPC1 or NPC2 genes. The products of these genes encodes for components of a lysosomal machinery that transport different kinds of lipids across the lysosomal membrane. The main abnormalities of NPC1 de ciency phenotype is the accumulation of free cholesterol (FC) and sphingolipids (GL) in brain, liver and other organs cells. Neurodegeneration and hepato-splenomegaly are common ndings. The NPC disease, in his severe onset, leads to a precocious exitus, though the inhibition of glyco-SL synthesis by miglustat has shown some clinical bene t. Recently the physiopathological mechanism has been partly el…

SFINGOLIPIDOMICA DELLA NON ALCOHOLIC FATTY LIVER DISEASE IN BIOPSIE DI SOGGETTI CON STEATOSI METABOLICA E DA INFEZIONE DI HCV. STUDIO CINETICO DELLA SINTESI DEGLI SFINGOLIPIDI IN VITRO MEDIANTE UTILIZZO DI ISOTOPI STABILI.

A NOVEL APOB MUTATION IDENTIFIED BY EXOME SEQUENCING COSEGREGATES WITH STEATOSIS, LIVER CANCER AND HYPOCHOLESTEROLEMIA

Objective. In familial hypobetalipoproteinemia (FHBL), fatty liver is a characteristic feature, and there are several reports of associated cirrhosis and hepatocarcinoma. We investigated a large kindred in which low-density lipoprotein (LDL) cholesterol, fatty liver and hepatocarcinoma displayed an autosomal dominant pattern of inheritance. Approach and Results. The proband was a 25 year-old female with low plasma cholesterol and hepatic steatosis. Low plasma levels of total cholesterol and fatty liver were observed in 10 more family members; 1 member was affected by liver cirrhosis and four more subjects died of either hepatocarcinoma or carcinoma on cirrhosis. To identify the causal mutat…

Metabolomic analysis of plasma from Alzheimer disease patients

Alzheimer Disease is a degenerative disease characterized by progressive impairment of cognitive function. The main feature of AD the generation of an abnormal peptide, beta amyloid 42 (Ab42) from Amyloid Precursor Protein (APP). Ab42 is the main constituent of neurotangles and amyloid plaques, microscopic lesions found in AD patients brain. Ab42 triggers an inflammatory response that is responsible for most of the observed tissue damage. The diagnosis of AD is a complex task, mostly based on imaging techniques and clinical evaluation of the patient’s neurological and cognitive functions. The search for plasma biomarkers able to detect early mild cognitive impairment is one of the recent at…

REDUCTION OF CHOLESTEROL WITH NUTRACEUTICAL: RESULTS OF A DOUBLE BLIND STUDY

A large body of evidence has demonstrated that LDL-C reduction by statins decrease cardiovascular risk. Statin treatment may also lead to non-lipid effects which may improve vascular protection, including an amelioration of endothelial function. On the other hand, despite a good tolerability demonstrated by several studies, statin treatment may lead to side effects, in particular when higher dosages are used. Alternative hypolipidemic treatments are nutraceuticals which are a food, or part of a food, that provides medical bene ts. Due to the low ef cacy associated to a high tolerability, patients with mild or moderate risk and/or statin-intolerant subjects are the best target of nutraceutic…

RUOLO DEL POLIMORFISMO ILE148MET DEL GENE PNPLA3 NELLA STEATOSI ASSOCIATA ALLA IPOBETALIPOPROTEINEMIA FAMILIARE

Erratum: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer's disease (Analytical and Bioanalytical Chemistry DOI: 10.1007/s00216-015-9229-6)

Erratum to: FragClust and TestClust, two informatics tools for chemical structure hierarchical clustering analysis applied to lipidomics. The example of Alzheimer’s disease

LIPIDOMICS OF FATTY LIVER IN NAFLD AND HCV INFECTION: LIVER SPHYNGOLIPIDS AND FATTY ACIDS

Lipids are used by the liver mainly for energy storage and membrane building, but they also contribute to cell signaling. Fatty liver is characterized by activation of metabolic and inflammatory pathways. In this work differences in lipidomic profiles of sphyngolipids (SL) and fatty acids (FA) have been evaluated in biopsies from 10 NAFLD patients, 22 (14 FL, 8 w/o FL) HCV patients and 13 healthy controls. FL is characterized by increased content of the main FA as myristic, palmitic, oleic, linoleic, saturated and monounsaturated FA in both model. FL of HCV is characterized by a more severe degree of cell damage and fibrosis associated with an increase of palmitoleic acid, long chain SL and…