Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid droplets (LDs) are subcellular organelles that store large amounts of the neutral lipids, triglycerides (TG) and/or cholesteryl esters (CE). LDs are commonly formed in adipocytes, liver cells and macrophages, and their formation has been shown to be associated with the progression of metabolic diseases, i.e., obesity, fatty liver and atherosclerosis. Interestingly, LDs are also found in some tumor tissues. We recently showed that LDs are prevalent in glioblastoma (GBM), the most deadly brain tumor, but are not detectable in low-grade gliomas and normal brain tissues, suggesting that LDs may serve as a novel diagnostic biomarker for GBM. This short review will briefly introduce LD biology, summarize recent observations about LDs in several types of cancer tissues, and discuss LD formation in GBM. Moreover, we will highlight the role of SOAT1 (sterol-O transferase 1), a key enzyme regulating CE synthesis and LD formation in GBM, in the regulation of SREBP (sterol regulatory-element binding protein) activation. The therapeutic potential of LDs and SOAT1 will be discussed.
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PMID:Lipid droplets, potential biomarker and metabolic target in glioblastoma. 2903 62

Loss-of-function (LOF) mutations in ANGPTL3, an inhibitor of lipoprotein lipase (LPL), cause a drastic reduction of serum lipoproteins and protect against the development of atherosclerotic cardiovascular disease. Therefore, ANGPTL3 is a promising therapy target. We characterized the impacts of ANGPTL3 depletion on the immortalized human hepatocyte (IHH) transcriptome, lipidome and human plasma lipoprotein lipidome. The transcriptome of ANGPTL3 knock-down (KD) cells showed altered expression of several pathways related to lipid metabolism. Accordingly, ANGPTL3 depleted IHH displayed changes in cellular overall fatty acid (FA) composition and in the lipid species composition of several lipid classes, characterized by abundant n-6 and n-3 polyunsaturated FAs (PUFAs). This PUFA increase coincided with an elevation of lipid mediators, among which there were species relevant for resolution of inflammation, protection from lipotoxic and hypoxia-induced ER stress, hepatic steatosis and insulin resistance or for the recovery from cardiovascular events. Cholesterol esters were markedly reduced in ANGPTL3 KD IHH, coinciding with suppression of the SOAT1 mRNA and protein. ANGPTL3 LOF caused alterations in plasma lipoprotein FA and lipid species composition. All lipoprotein fractions of the ANGPTL3 LOF subjects displayed a marked drop of 18:2n-6, while several highly unsaturated triacylglycerol (TAG) species were enriched. The present work reveals distinct impacts of ANGPTL3 depletion on the hepatocellular lipidome, transcriptome and lipid mediators, as well as on the lipidome of lipoproteins isolated from plasma of ANGPTL3-deficient human subjects. It is important to consider these lipidomics and transcriptomics findings when targeting ANGPTL3 for therapy and translating it to the human context.
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PMID:ANGPTL3 deficiency alters the lipid profile and metabolism of cultured hepatocytes and human lipoproteins. 3215 67