Using the Synergy between HPLC-MS and MALDI-MS Imaging to Explore the Lipidomics of Clear Cell Renal Cell Carcinoma.

Lipid imaging mass spectrometry (LIMS) has been tested in several pathological contexts, demonstrating its ability to segregate and isolate lipid signatures in complex tissues, thanks to the technique's spatial resolution. However, it cannot yet compete with the superior identification power of high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS), and therefore, very often, the latter is used to refine the assignment of the species detected by LIMS. Also, it is not clear if the differences in sensitivity and spatial resolution between the two techniques lead to a similar panel of biomarkers for a given disease.

High-Resolution Human Kidney Molecular Histology by Imaging Mass Spectrometry of Lipids.

For many years, traditional histology has been the gold standard for the diagnosis of many diseases. However, alternative and powerful techniques have appeared in recent years that complement the information extracted from a tissue section. One of the most promising techniques is imaging mass spectrometry applied to lipidomics.

A simple and reproducible method for quantification of human tear lipids with ultrahigh-performance liquid chromatography-mass spectrometry.

Purpose: The purpose was to select a simple and reproducible method for lipid measurements of human tears with ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS). Two sample preparation procedures were evaluated and compared: the Bligh and Dyer (BD) liquid-liquid extraction method with chloroform and methanol and protein precipitation with isopropanol (IPA).

Methods: Reproducibility and recovery efficiencies of 20 non-endogenous internal lipid standards were tested in 10-µl tear samples from healthy subjects.

Molecular and cellular insights into the role of SND1 in lipid metabolism.

Staphylococcal nuclease and Tudor domain containing 1 (SND1) is an evolutionarily conserved protein present in eukaryotic cells from protozoa to mammals. SND1 has gained importance because it is overexpressed in aggressive cancer cells and diverse primary tumors. Indeed, it is regarded as a marker of cancer malignity.

Channeling of newly synthesized fatty acids to cholesterol esterification limits triglyceride synthesis in SND1-overexpressing hepatoma cells.

SND1 is a putative oncoprotein whose molecular function remains unclear. Its overexpression in hepatocellular carcinoma impairs cholesterol homeostasis due to the altered activation of the sterol regulatory element-binding protein (SREBP) 2, which results in the accumulation of cellular cholesteryl esters (CE). In this work, we explored whether high cholesterol synthesis and esterification originates changes in glycerolipid metabolism that might affect cell growth, given that acetyl-coenzyme A is required for cholesterogenesis and fatty acids (FA) are the substrates of acyl-coenzyme A:cholesterol acyltransferase (ACAT).

High-fat diet overfeeding promotes nondetrimental liver steatosis in female mice.

High-fat diet (HFD) feeding or leptin-deficient mice are extensively used as models resembling features of human nonalcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild-type (WT) and ob/ ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia.

Adenosine: Direct and Indirect Actions on Gastric Acid Secretion.

Composed by a molecule of adenine and a molecule of ribose, adenosine is a paradigm of recyclable nucleoside with a multiplicity of functions that occupies a privileged position in the metabolic and regulatory contexts. Adenosine is formed continuously in intracellular and extracellular locations of all tissues. Extracellular adenosine is a signaling molecule, able to modulate a vast range of physiologic responses in many cells and organs, including digestive organs.

Expression of Adenosine A Receptor and Adenosine Deaminase in Rabbit Gastric Mucosa ECL Cells.

Adenosine is readily available to the glandular epithelium of the stomach. Formed continuously in intracellular and extracellular locations, it is notably produced from ATP released in enteric cotransmission. Adenosine analogs modulate chloride secretion in gastric glands and activate acid secretion in isolated parietal cells through A adenosine receptor (A2BR) binding.

SND1 overexpression deregulates cholesterol homeostasis in hepatocellular carcinoma.

SND1 is a multifunctional protein participating, among others, in gene transcription and mRNA metabolism. SND1 is overexpressed in cancer cells and promotes viability and tumourigenicity of hepatocellular carcinoma cells. This study shows that cholesterol synthesis is increased in SND1-overexpressing hepatoma cells.

Stimulation of gastric acid secretion by rabbit parietal cell A(2B) adenosine receptor activation.

Adenosine modulates different functional activities in many cells of the gastrointestinal tract; some of them are believed to be mediated by interaction with its four G protein-coupled receptors. The renewed interest in the adenosine A2B receptor (A2BR) subtype can be traced by studies in which the introduction of new genetic and chemical tools has widened the pharmacological and structural knowledge of this receptor as well as its potential therapeutic use in cancer and inflammation- or hypoxia-related pathologies. In the acid-secreting parietal cells of the gastric mucosa, the use of various radioligands for adenosine receptors suggested the presence of the A2 adenosine receptor subtype(s) on the cell surface.

Cholesterol mobilization from hepatic lipid droplets during endotoxemia is altered in obese ob/ob mice.

The innate immune response to pathogens during the acute phase response includes lipid metabolism adaptations. Hepatic triacylglycerol (TG) and cholesteryl ester (CE) storage in and mobilization from lipid droplets (LDs) respond to metabolic changes under the control of liver X receptor (LXR) transactivation and cytokine transduction. To evaluate whether alterations of these mechanisms have an impact in the adaptive response to endotoxemia, we analysed liver metabolism changes in lipopolysaccharide (LPS)-treated ob/ob mice, which show altered metabolic and innate responses and a higher sensitivity to sepsis.

Involvement of lipid droplets in hepatic responses to lipopolysaccharide treatment in mice.

Infection and inflammation induce important changes in lipid metabolism, which result in increased free fatty acids and triacylglycerol in plasma and altered high density lipoprotein (HDL) metabolism. Our aim was to elucidate whether hepatic lipid droplets (LDs) are involved in the adaptations of lipid metabolism to endotoxemia. We characterized the lipid content and several enzymatic activities in subcellular fractions and subpopulations of LDs from livers of mice 24h after lipopolysaccharide (LPS) treatment and analyzed the expression of key genes involved in lipid management.

Infection of primary hepatocytes with adenoviral vectors alters biliary lipid metabolism.

In the context of a study of the involvement of SND1 (also known as coactivator p100) in biliary lipid secretion by primary rat hepatocytes, first-generation adenoviral vectors were used to promote the overexpression and underexpression of the protein SND1. Although differential expression of SND1 did not result in significant changes in the processes studied, some effects of the adenoviral infection itself were observed. In particular, infected hepatocytes showed a higher intracellular taurocholate accumulation capacity.

A role for transcription factor E2F2 in hepatocyte proliferation and timely liver regeneration.

E2F transcription factors are key regulators of the cell cycle although the relative contribution of each E2F member in regulating cellular proliferation is still poorly defined. Present evidence suggests that E2F2 may act both as a suppressor and promoter of proliferation, depending on the cellular context. We used a loss-of-function mutant mouse model to investigate the function of E2F2 in liver regeneration after partial hepatectomy, a paradigm of cell-cycle progression.

Lipid analysis reveals quiescent and regenerating liver-specific populations of lipid droplets.

The mammalian liver, a key organ in lipid homeostasis, can accumulate increased amounts of lipids in certain physiological conditions including liver regeneration. Lipid droplets (LD), the lipid storage organelles in the cytoplasm, are composed of a core of neutral lipids (mainly triacylglycerols and cholesteryl esters) surrounded by a monolayer of phospholipids and cholesterol with associated proteins. It is recognized that LD lipid composition is cell- and environment-specific and enables LD to carry out specific functions, but few descriptive studies aiming to interpret such differences have been published.