Laurence Mabile

Shift Work and Metabolic Syndrome: Respective Impacts of Job Strain, Physical Activity, and Dietary Rhythms

The impact of shift work on cardiovascular disease (CVD) risk factors and metabolic syndrome are not yet completely understood. The objectives of this study were to evaluate the impact of shift work on metabolic syndrome according to two different definitions in a population of strictly rotating shift workers (3×8 h) compared to paired counterparts working only day hours, and to study whether shift work itself is a determinant of metabolic syndrome after taking into account a large panel of confusing factors. We conducted a cross‐sectional study comparing 98 strictly rotating shift workers to 100 regular day‐workers (all subjects had a long experience of their working rhythms) within the same petrochemical plant. Clinical, behavioral, occupational, and biological data were collected, and a detailed nutritional investigation was done. Shift and day workers were comparable in terms of major CVD factors, and both had a 10 yr Framingham risk scoring of 11%. Shift workers reported an increased job strain and higher total and at‐work physical activity. Alterations in metabolic parameters were evident with a rise in triglycerides, free fatty acids, and gamma glutamyl transpeptidase and lower HDL‐cholesterol. Multiple logistic regression analysis demonstrated that shift work was associated with occurrence of metabolic syndrome, as defined by the National Cholesterol Education Program‐ATPIII criteria, OR: 2.38 (1.13–4.98), but not using the more recent score from the International Diabetes Federation, which gives a major emphasis on abdominal obesity. Total energy intake and contributions of the major nutrients did not differ between the two groups, with the notable exception of saturated lipids (+10% in shift workers). Meal distribution was clearly different: energy intake was more fractionated within the day, with a lesser contribution of breakfast and lunch but with increased intakes during intermediate light meals, particularly in the afternoon and night. Multivariate analyses were performed to test for the influence of dietary rhythms on the development of an NCEP‐ATPIII metabolic syndrome. Dietary intakes at breakfast and during intermediate light meals appear to be “protective” against metabolic syndrome, while a high load at dinner favors its occurrence. A high intake at lunch is particularly deleterious to shift workers. However, in all tested models, shift work remained significantly associated with metabolic syndrome, after taking into account potential covariates like job strain, physical activity, quantitative dietary parameters, and meal distribution. A specific follow‐up of shift workers should be recommended to occupational physicians.

Hepatic lipase structure/function relationship, synthesis, and regulation

Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries. In humans, the enzyme is mostly bound onto heparan-sulfate proteoglycans at the surface of hepatocytes and also of sinusoid endothelial cells. HL shares a number of functional domains with lipoprotein lipase and with other members of the lipase gene family. It is a secreted glycoprotein, and remodelling of the N-linked oligosaccharides appears to be crucial for the secretion process, rather than for the acquisition of the catalytic activity. HL is also present in adrenals and ovaries, where it might promote delivery of lipoprotein cholesterol for steroidogenesis. However, evidence of a local synthesis is still controversial. HL activity is fairly regulated according to the cell cholesterol content and to the hormonal status. Coordinate regulations have been reported for both HL and the scavenger-receptor B-I, suggesting complementary roles in cholesterol metabolism. However, genetic variants largely contribute to HL variability and their possible impact in the development of a dyslipidemic phenotype, or in a context of insulin-resistance, is discussed.

Mitochondrial Function Is Involved in LDL Oxidation Mediated by Human Cultured Endothelial Cells

Human endothelial cells (ECs) grown under standard conditions are able to generate a basal level of oxygen free radicals and induce progressive oxidation of LDLs. Inhibition of cell-mediated LDL oxidation by superoxide dismutase, EDTA, or desferrioxamine implicates a role for superoxide anion and/or transition metals in this process. The potential role of the mitochondrion was investigated by inducing mitochondrial deenergization by selective photosensitization or the addition of inhibitors of the mitochondrial respiratory chain. Mitochondria of human cultured ECs were selectively damaged by photosensitization of cells labeled with the mitochondrion-selective fluorescent dye 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide under conditions that induced only low levels of toxicity during the time of the experiment. Photosensitized ECs exhibited severe mitochondrial dysfunction, as suggested by the defect in mitochondrial uptake of the mitochondrion-selective fluorescent dyes [rhodamine 123 and 2-(4-dimethylaminostyryl)-1-methylpyridinium iodide] and morphological alterations as shown by transmission electron microscopy. In mitochondria-photosensitized cells, superoxide anion generation was strongly decreased, as was LDL oxidation and the subsequent cytotoxicity. When ECs were incubated with the mitochondrial respiratory-chain inhibitors antimycin A or rotenone or with the carbonylcyanide-m-chlorophenylhydrazone uncoupler rhodamine 123, uptake and subcellular distribution were altered, and concomitantly superoxide anion production and LDL oxidation were strongly decreased. In conclusion, these data suggest that mitochondrial function is required, directly or indirectly, for the production of superoxide anion and the subsequent LDL oxidation by human vascular ECs.

The role of a bioresource research impact factor as an incentive to share human bioresources

The role of a bioresource research impact factor as an incentive to share human bioresources

α-tocopherol, ascorbic acid, and rutin inhibit synergistically the copper-promoted LDL oxidation and the cytotoxicity of oxidized LDL to cultured endothelial cells

Low-density lipoproteins (LDL) mildly oxidized by copper ions or UV radiations exhibit a cytotoxic effect to cultured endothelial cells. Rutin, a polyphenolic flavonoid, ascorbic acid, and α-tocopherol were able to inhibit the peroxidation of LDL and their subsequent cytotoxicity. The mixture of the three compounds (rutin/ascorbic acid/α-tocopherol, 4/4/1) exhibited a supra-additive antioxidant effect. The inhibition of the cytotoxic effect was well correlated with that of TBARS formation. Another important conclusion is that these antioxidants were able to prevent directly at the cellular level the cytotoxic effect of oxidized LDL, since cells preincubated with them were protected against the cytotoxic effect of previously oxidized LDL. The protective effect of antioxidants was limited because of their own toxicity. The antioxidant mixture permitted a maximal cytoprotective effect with relatively lower concentrations to be obtained and the cytotoxicity of high concentrations to be avoided. In conclusion, rutin, ascorbic acid, and α-tocopherol constitute two lines of defense in protecting cells against injury owing to oxidation of LDL (1) at the LDL level, by inhibiting the LDL oxidation and the subsequent cytotoxicity, and (2) at the cellular level, by protecting the cells directly, i.e., by increasing their resistance against the cytotoxic effect of oxidized LDL.

The embodiment of adverse childhood experiences and cancer development: potential biological mechanisms and pathways across the life course

ObjectivesTo explore current evidence of the physiological embedding of stress to discuss whether adverse childhood experiences (ACE) causing chronic or acute stress responses may alter fundamental biological functions.MethodsA non-systematic review of the literature was carried out using keyword searches in Pubmed and the web of science from May to October 2011. In reference to the literature identified, we examine the potential biological pathways potentially linking exposure to ACE and cancer development and progression in adulthood.ResultsThese mechanisms, in interaction with social position, and mediated by subsequent environmental exposures, may ultimately lead to the development of cancer. The experience of acute or chronic stressors during sensitive periods of childhood development which can induce several known biological responses, are likely to have an impact on subsequent biological and behavioural functions depending on the timing of initial exposures, and subsequently mediated by later exposures. For this reason, childhood exposure to adversity is a likely source of both acute and chronic stressors, and can be examined as an important initial exposure on a pathway towards adult ill health.ConclusionsSuch pathways justify a life course approach to understanding cancer aetiology, which may have its origins early in life.

α-tocopherol and trolox block the early intracellular events (TBARS and calcium rises) elicited by oxidized low density lipoproteins in cultured endothelial cells

Abstract Low-density lipoproteins (LDLs), treated by UV-C radiations under conditions permitting mildly oxidized LDL (6 ± 2 nmol TBARS/mg apoB, without major structural or functional alteration of apoB), have been used for studying their cytotoxicity to cultured bovine aortic endothelial cells and the cytoprotective effect of various analogs of a-tocopherol. Toxic doses of oxidized LDL evoked intracellular events, such as cellular thiobarbituric acid reactive substances (TBARS) and a sustained peak of [Ca2+]i (cytosolic calcium). The sustained [Ca2+]i peak seems to be directly involved in the genesis of cell injury leading to cell death in contrast to cellular TBARS, which seems to be either an earlier step of signal transduction or a side effect, as shown by inhibiting the [Ca2+]i rise by ethylene glycol-O,O′-bis(amino ethyl)-N1N1N1′N′-tetraacetic acid (EGTA) added just before the time of the [Ca2+]i peak. When a-tocopherol or trolox (α short-chain, water-soluble analog of α-tocopherol) were added to the culture medium simultaneously with oxidized LDL, they were able to increase the resistance of endothelial cells against the cytotoxic effect of oxidized LDL, whereas α-tocopheryl acetate and a-tocopheryl succinate were almost completely ineffective because of the liberation of only very low levels of α-tocopherol. Trolox exhibited a more potent cytoprotective effect than α-tocopherol (IC50: 1 ± 0.2and8 ± 2 μmol/l for trolox and α-tocopherol, respectively). As shown by preincubating cells with effective concentrations of α-tocopherol or trolox, the cytoprotective effect was completely independent of any inhibition of LDL oxidation and was remanent for 2 d with α-tocopherol or for 3–4 d with trolox. Cytoprotective concentrations of trolox and α-tocopherol did not inhibit LDL uptake but acted at the cellular level by blocking the formation of cellular TBARS and the sustained [Ca2+]i peak as well. The potential relevance of these data in relation to the prevention of atherosclerosis is discussed.

Quantifying the use of bioresources for promoting their sharing in scientific research

An increasing portion of biomedical research relies on the use of biobanks and databases. Sharing of such resources is essential for optimizing knowledge production. A major obstacle for sharing bioresources is the lack of recognition for the efforts involved in establishing, maintaining and sharing them, due to, in particular, the absence of adequate tools. Increasing demands on biobanks and databases to improve access should be complemented with efforts of end-users to recognize and acknowledge these resources. An appropriate set of tools must be developed and implemented to measure this impact.To address this issue we propose to measure the use in research of such bioresources as a value of their impact, leading to create an indicator: Bioresource Research Impact Factor (BRIF). Key elements to be assessed are: defining obstacles to sharing samples and data, choosing adequate identifier for bioresources, identifying and weighing parameters to be considered in the metrics, analyzing the role of journal guidelines and policies for resource citing and referencing, assessing policies for resource access and sharing and their influence on bioresource use. This work allows us to propose a framework and foundations for the operational development of BRIF that still requires input from stakeholders within the biomedical community.

Developing a guideline to standardize the citation of bioresources in journal articles (CoBRA)

BackgroundMany biomedical publications refer to data obtained from collections of biosamples. Sharing such bioresources (biological samples, data, and databases) is paramount for the present governance of research. Recognition of the effort involved in generating, maintaining, and sharing high quality bioresources is poorly organized, which does not encourage sharing. At publication level, the recognition of such resources is often neglected and/or highly heterogeneous. This is a true handicap for the traceability of bioresource use. The aim of this article is to propose, for the first time, a guideline for reporting bioresource use in research articles, named CoBRA: Citation of BioResources in journal Articles.MethodsAs standards for citing bioresources are still lacking, the members of the journal editors subgroup of the Bioresource Research Impact Factor (BRIF) initiative developed a standardized and appropriate citation scheme for such resources by informing stakeholders about the subject and raising awareness among scientists and in science editors’ networks, mapping this topic among other relevant initiatives, promoting actions addressed to stakeholders, launching surveys, and organizing focused workshops.ResultsThe European Association of Science Editors has adopted BRIF’s suggestion to incorporate statements on biobanks in the Methods section of their guidelines. The BRIF subgroup agreed upon a proposed citation system: each individual bioresource that is used to perform a study and that is mentioned in the Methods section should be cited as an individual “reference [BIORESOURCE]” according to a delineated format. The EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network mentioned the proposed reporting guideline in their “guidelines under development” section.ConclusionsEvaluating bioresources’ use and impact requires that publications accurately cite such resources. Adopting the standard citation scheme described here will improve the quality of bioresource reporting and will allow their traceability in scientific publications, thus increasing the recognition of bioresources’ value and relevance to research.Please see related article: http://dx.doi.org/10.1186/s12916-015-0284-9.

OXIDIZABILITY AND SUBSEQUENT CYTOTOXICITY OF CHYLOMICRONS TO MONOCYTIC U937 AND ENDOTHELIAL CELLS ARE DEPENDENT ON DIETARY FATTY ACID COMPOSITION

Oxidized chylomicrons may be a metabolic factor involved in the injury of the arterial wall and may constitute a potential link between postprandial lipemia and atherogenesis. It was of interest to study the influence of dietary fatty acid composition on the oxidizability and subsequent cytotoxicity of chylomicrons on cultured cells. Human chylomicrons were obtained from healthy volunteers 3 h after ingestion of a triglyceride-rich meal containing mainly either polyunsaturated fatty acids (soya oil) or monounsaturated fatty acids (olive oil) or saturated fatty acids (partly hydrogenated palm oil). Polyunsaturated fatty acid (PUFA)-rich chylomicrons exhibited a high oxidizability, whereas chylomicrons enriched with monounsaturated or saturated fatty acids were relatively resistant to oxidation. The cytotoxicity of various types of chylomicrons submitted to oxidation has been tested comparatively on cultured human monocytic U937 cells and endothelial cells. Chylomicrons enriched with saturated and monounsaturated fatty acids were not or only slightly cytotoxic to cultured cells, whereas PUFA-rich chylomicrons (highly susceptible to oxidation) were highly cytotoxic. The influence of cholesterol on the oxidizability and subsequent cytotoxicity of PUFA-rich chylomicrons has been investigated by using comparatively a soya diet supplemented or not with cholesterol. PUFA-rich cholesterol-rich chylomicrons were slightly more oxidizable and more cytotoxic than PUFA-rich (cholesterol-poor) chylomicrons, thus suggesting that the cytotoxicity of PUFA-rich chylomicrons may be due to oxidation derivatives of PUFA (for the major part) and to oxysterols (for a minor part). Furthermore, the cytotoxic effects of oxidized PUFA-rich chylomicrons and of mildly oxidized LDL were in similar range (even higher for PUFA-rich chylomicrons when expressed per lipoprotein particle), thus suggesting that oxidized PUFA-rich chylomicrons may play a nonnegligible role in cytotoxic events occurring during atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)