Anatomical distribution of lipids in human brain cortex by imaging mass spectrometry.

Molecular mass images of tissues will be biased if differences in the physicochemical properties of the microenvironment affect the intensity of the spectra. To address this issue, we have performed-by means of MALDI-TOF mass spectrometry-imaging on slices and lipidomic analysis in extracts of frontal cortex, both from the same postmortem tissue samples of human brain. An external calibration was used to achieve a mass accuracy of 10 ppm (1σ) in the spectra of the extracts, although the final assignment was based on a comparison with previously reported species. The spectra recorded directly from tissue slices (imaging) show excellent s/n ratios, almost comparable to those obtained from the extracts. In addition, they retain the information about the anatomical distribution of the molecular species present in autopsied frozen tissue. Further comparison between the spectra from lipid extracts devoid of proteins and those recorded directly from the tissue unambiguously show that the differences in lipid composition between gray and white matter observed in the mass images are not an artifact due to microenvironmental influences of each anatomical area on the signal intensity, but real variations in the lipid composition.

Interleukin-6 is associated with liver lipid homeostasis but not with cell death in experimental hepatic steatosis.

Hepatic steatosis is a risk factor for the progression of non-alcoholic fatty liver disease. The role of pro-inflammatory interleukin (IL)-6 in hepatic steatosis etiology is controversial. We investigated in vivo and in primary hepatocyte cultures whether IL-6 has a modulator role in liver and mitochondria lipid composition and cell death in a choline-deficient (CD) diet rat model of hepatic steatosis. Dietary choline deficiency increased triglycerides and cholesterol, and reduced phosphatidylcholine (PC), phosphatidylethanolamine (PE) and the membrane integrity marker PC:PE ratio in liver. Choline-deficient diet enhanced systemic IL-6, and IL-6 receptor expression and cell death vulnerability in hepatocytes. Derangement of the mitochondrial electron transport chain and of its phospholipid environment was found in CD rat liver mitochondria, which exhibited elevated concentrations of triglycerides, cardiolipin and PC and elevated PC:PE ratio. The cell treatment with IL-6, but not PC, eliminated much of the CD-promoted lipid imbalance in mitochondria but not tumor-necrosis factor (TNF)-alpha-induced cell death. However, PC supplementation prevented the TNF-alpha-induced DNA fragmentation, cytochrome-c release and caspase-3 activity in control and CD hepatocytes. In conclusion, IL-6 ameliorated the mitochondria lipid disturbance in hepatocytes isolated from steatotic animals. Furthermore, PC is identified as a new survival agent that reverses several TNFalpha-inducible responses that are likely to promote steatosis and necrosis.

Hepatic VLDL assembly is disturbed in a rat model of nonalcoholic fatty liver disease: is there a role for dietary coenzyme Q?

The overproduction of very-low-density lipoprotein (VLDL) is a characteristic feature of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to use a high-fat diet-induced model of NAFLD in rats to investigate 1) the influence of the disease on hepatic VLDL processing in the endoplasmic reticulum and 2) the potential modulatory effects of dietary coenzyme Q (CoQ). Rats were fed a standard low-fat diet (control) or a diet containing 35% fat (57% metabolizable energy). After 10 wk, high-fat diet-fed animals were divided into three groups: the first group was given CoQ9 (30 mg*kg body wt(-1)*day(-1) in 0.3 ml olive oil), the second group was given olive oil (0.3 ml/day) only, and the third group received no supplements. Feeding (3 high-fat diets and the control diet) was then continued for 8 wk. In all high-fat diet-fed groups, the content of triacylglycerol (TG) and cholesterol in plasma VLDL, the liver, and liver microsomes was increased, hepatic levels of apolipoprotein B48 were raised, and the activities of microsomal TG transfer protein and acyl CoA:cholesterol acyltransferase were reduced. These findings provide new evidence indicating that VLDL assembly and the inherent TG transfer to the endoplasmic reticulum are altered in NAFLD and suggest a possible explanation for both the overproduction of VLDL associated with the condition and the disease etiology itself. Dietary CoQ caused significant increases in apolipoprotein B mRNA and microsomal TG levels and altered the phospholipid content of microsomal membranes. These changes, however, may not be beneficial as they may lead to the secretion of larger, more atherogenic VLDL.