Dietary alleviation of maternal obesity and diabetes: increased resistance to diet-induced obesity transcriptional and epigenetic signatures.

According to the developmental origins of health and diseases (DOHaD), and in line with the findings of many studies, obesity during pregnancy is clearly a threat to the health and well-being of the offspring, later in adulthood. We previously showed that 20% of male and female inbred mice can cope with the obesogenic effects of a high-fat diet (HFD) for 20 weeks after weaning, remaining lean. However the feeding of a control diet (CD) to DIO mice during the periconceptional/gestation/lactation period led to a pronounced sex-specific shift (17% to 43%) from susceptibility to resistance to HFD, in the female offspring only.

Liver x receptor regulates arachidonic acid distribution and eicosanoid release in human macrophages: a key role for lysophosphatidylcholine acyltransferase 3.

Objective: Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that are highly expressed in macrophages and regulate lipid homeostasis and inflammation. Among putative LXR target genes, lysophosphatidylcholine acyltransferase 3 (LPCAT3) involved in the Lands cycle controls the fatty acid composition at the sn-2 position of glycerophospholipids and, therefore, the availability of fatty acids, such as arachidonic acid (AA), used for eicosanoid synthesis. The aim of our study was to determine whether LXRs could regulate the Lands cycle in human macrophages, to assess the consequences in terms of lipid composition and inflammatory response, and to work out the relative contribution of LPCAT3 to the observed changes.

Knock-down of the oxysterol receptor LXRα impairs cholesterol efflux in human primary macrophages: lack of compensation by LXRβ activation.

Liver X Receptors (LXRs) α and β are oxysterol-activated nuclear receptors involved in the control of lipid metabolism and inflammation. Pharmacological activation of LXR is promising in the treatment of atherosclerosis since it can promote cholesterol efflux from macrophages and prevent foam cell formation. However, the development of LXR agonists has been limited by undesirable side-effects such as hepatic steatosis mediated by LXRα activation.

Validation of a reference method for total cholesterol measurement in human serum and assignation of reference values to proficiency testing samples.

Objectives: Our objective was to develop a reference method to measure total cholesterol in human serum, in order to assign values and assess the accuracy of field methods in French clinical laboratories.

Design And Methods: A reference method based on gas chromatography coupled with mass spectrometry and isotope dilution (GC-IDMS) was developed and validated. It was then used to assign reference values to five frozen serum samples from voluntary proficiency testing schemes gathering 170 French clinical laboratories.

Identification of biological markers of liver X receptor (LXR) activation at the cell surface of human monocytes.

Background: Liver X receptor (LXR) α and LXR β (NR1H3 and NR1H2) are oxysterol-activated nuclear receptors involved in the control of major metabolic pathways such as cholesterol homeostasis, lipogenesis, inflammation and innate immunity. Synthetic LXR agonists are currently under development and could find applications in various fields such as cardiovascular diseases, cancer, diabetes and neurodegenerative diseases. The clinical development of LXR agonists requires the identification of biological markers for pharmacodynamic studies.

Pravastatin reverses the membrane cholesterol reorganization induced by myocardial infarction within lipid rafts in CD14(+)/CD16(-) circulating monocytes.

Large numbers of monocytes are recruited in the infarcted myocardium. Their cell membranes contain cholesterol-rich microdomains called lipids rafts, which participate in numerous signaling cascades. In addition to its cholesterol-lowering effect, pravastatin has several pleiotropic effects and is widely used as secondary prevention treatment after myocardial infarction (MI).

Increased erythrocytes n-3 and n-6 polyunsaturated fatty acids is significantly associated with a lower prevalence of steatosis in patients with type 2 diabetes.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome and type 2 diabetes. Although dietary fat contributes substantially to the accumulation of liver fat, the role of individual fatty acids in this accumulation is unclear.

Objective: In this study, we set out to determine whether liver fat content (LFC), was associated with red blood cell fatty acid (RBC-FA) composition in people with type 2 diabetes.

PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes.

Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance.

Objective: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes.

Design, Setting And Participants: Two hundred and thirty-four patients with type 2 diabetes were included in this study.

Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells.

trans-Resveratrol has been proposed to prevent tumor growth and to sensitize cancer cells to anticancer agents. Polyphenol entry into the cells has remained poorly understood. Here, we show that [(3)H]-resveratrol enters colon cancer cells (SW480, SW620, HT29) and leukemia U937 cells through a monensin (5-20 μmol/L) -sensitive process that suggests clathrin-independent endocytosis.

Impact of obesity on the prognostic value of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with acute myocardial infarction.

Objective: To examine the influence of obesity on the predictive value of the pro-B-type natriuretic peptide (NT-proBNP) assay in acute myocardial infarction.

Design: Prospective observational study.

Setting: All intensive care units in one region of France.

Substrate specificity overlap and interaction between adrenoleukodystrophy protein (ALDP/ABCD1) and adrenoleukodystrophy-related protein (ALDRP/ABCD2).

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder caused by mutations in the ABCD1 gene, which encodes a peroxisomal member of the ATP-binding cassette (ABC) transporter subfamily D called ALDP. ALDP is supposed to function as a homodimer allowing the entry of CoA-esters of very-long chain fatty acids (VLCFA) into the peroxisome, the unique site of their β-oxidation. ALDP deficiency can be corrected by overexpression of ALDRP, its closest homolog.

Changes in apolipoprotein B100-containing lipoprotein metabolism due to an estrogen plus progestin oral contraceptive: a stable isotope kinetic study.

Context: Oral contraceptives with estrogen plus progestin are likely to influence apolipoprotein B (apoB)-containing lipoprotein metabolism by changing the expression of different enzymes or receptors that play a major role in this metabolism. However, the precise changes in apoB kinetic parameters induced by oral contraceptives that are now currently used are unknown.

Objectives: We studied the impact of Moneva, containing 30 microg ethinylestradiol and 75 microg gestodene, on the apoB production rate and fractional catabolic rate of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL).

TRPC1 is regulated by caveolin-1 and is involved in oxidized LDL-induced apoptosis of vascular smooth muscle cells.

Oxidized low-density lipoprotein (oxLDL) induced-apoptosis of vascular cells may participate in plaque instability and rupture. We have previously shown that vascular smooth muscle cells (VSMC) stably expressing caveolin-1 were more susceptible to oxLDL-induced apoptosis than VSMC expressing lower level of caveolin-1, and this was correlated with enhanced Ca(2+) entry and pro-apoptotic events. In this study, we aimed to identify the molecular events involved in oxLDL-induced Ca(2+) influx and their regulation by the structural protein caveolin-1.

Increased apolipoprotein AI production rate and redistribution of high-density lipoprotein size induced by estrogen plus progestin as oral contraceptive.

Context: The impact of estrogen plus progestin as an oral contraceptive on high density lipoprotein (HDL) apolipoprotein (apo) AI metabolism in humans is poorly understood.

Objectives: This study was designed to measure the in vivo effect of Moneva (30 microg ethinylestradiol, 75 microg gestodene) on HDL apoAI production rate and fractional catabolic rate.

Design: Using (13)C-leucine, we performed two kinetic studies in the fed state in 10 normolipidemic young women, before and 3 months after beginning Moneva.

Liver X receptor-mediated induction of cholesteryl ester transfer protein expression is selectively impaired in inflammatory macrophages.

Objective: Cholesteryl ester transfer protein (CETP) is a target gene for the liver X receptor (LXR). The aim of this study was to further explore this regulation in the monocyte-macrophage lineage and its modulation by lipid loading and inflammation, which are key steps in the process of atherogenesis.

Methods And Results: Exposure of bone marrow-derived macrophages from human CETP transgenic mice to the T0901317 LXR agonist increased CETP, PLTP, and ABCA1 mRNA levels.

Wine and oxidative stress: up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans.

Wine and alcohol consumption has been considered to be protective against coronary heart disease development, an oxidative stress associated disease. Wine contains polyphenols displaying antioxidant properties tested in in vitro and in vivo studies. Due to this, a general consensus exists, both among the general public and the scientific community, that wine, particularly red wine, is an antioxidant beverage.

Induction of transglutaminase 2 by a liver X receptor/retinoic acid receptor alpha pathway increases the clearance of apoptotic cells by human macrophages.

Rationale: Liver X receptors (LXRs) are oxysterol-activated nuclear receptors that are involved in the control of cholesterol homeostasis and inflammatory response. Human monocytes and macrophages express high levels of these receptors and are appropriate cells to study the response to LXR agonists.

Objective: The purpose of this study was to identify new LXR targets in human primary monocytes and macrophages and the consequences of their activation.

Prognostic value of N-terminal pro-brain natriuretic peptide in elderly people with acute myocardial infarction: prospective observational study.

Objective: To examine the influence of age on the predictive value of N-terminal pro-brain natriuretic (NT-proBNP) peptide assay in acute myocardial infarction.

Design: Prospective observational study.

Setting: All intensive care units in one French region.

Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes.

Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a reduction in plasma residence time, which may be detrimental. Rosuvastatin is the most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism in type 2 diabetes remain unknown. We performed a randomized double-blind cross-over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes.