Omental adipocyte hypertrophy relates to coenzyme Q10 redox state and lipid peroxidation in obese women

Occurrence of oxidative stress in white adipose tissues contributes to its dysfunction and the development of obesity-related metabolic complications. Coenzyme Q10 (CoQ10) is the single lipophilic antioxidant synthesized in humans and is essential for electron transport during mitochondrial respiration. To understand the role of CoQ10 in adipose tissue physiology and dysfunction, the abundance of the oxidized and reduced (CoQ10red) isoforms of the CoQ10 were quantified in subcutaneous and omental adipose tissues of women covering the full range of BMI (from 21.5 to 53.2 kg/m2). Lean women displayed regional variations of CoQ10 redox state between the omental and subcutaneous depot, despite similar total content. Obese women had reduced CoQ10red concentrations in the omental depot, leading to increased CoQ10 redox state and higher levels of lipid hydroperoxide. Women with low omental CoQ10 content had greater visceral and subcutaneous adiposity, increased omental adipocyte diameter, and higher circulating interleukin-6 and C-reactive protein levels and were more insulin resistant. The associations between abdominal obesity-related cardiometabolic risk factors and CoQ10 content in the omental depot were abolished after adjustment for omental adipocyte diameter. This study shows that hypertrophic remodeling of visceral fat closely relates to depletion of CoQ10, lipid peroxidation, and inflammation

Les espèces actives de l’oxygène : le yin et le yang de la mitochondrie

Il existe de nombreuses sources d’espèces actives de l’oxygène (EAO) dans la cellule ; malgré l’importance de chacune d’entre elles, la mitochondrie a été choisie comme sujet central de cet article en raison de son rôle primordial dans la bio-énergétique et du fait qu’elle constitue le site majeur de la production cellulaire d’EAO, 80 % de l’anion superoxyde provenant de la chaîne respiratoire. Cette production est indissociable du processus respiratoire et fortement modulée par les conditions environnementales : elle varie notamment selon l’intensité du métabolisme énergétique ou de la pression en oxygène, permettant aux cellules de s’adapter à ces changements environnementaux en activant des voies spécifiques de signalisation. Lorsque cette production d’EAO devient chronique, elle induit des effets délétères, le stress oxydant mitochondrial étant impliqué aussi bien en physiopathologie qu’au cours du vieillissement.Literature on reactive oxygen species (ROS) effects on cell biology and physiopathology is huge and appears to be controversial. This could be explained by the fact that very few studies take into account the real subcellular source of ROS production, their chemical nature and the intensity of their production. In spite of the importance of the other sites of ROS production in the cell, we decided to focus on mitochondrial ROS. Besides their key role in bioenergetics and ATP synthesis, mitochondria are one of the main sites of ROS generation within the cell. 80 % of intracellular superoxide anion is provided by the mitochondrial respiratory chain. Mitochondrial ROS production is closely associated with activity of the respiratory chain and is modulated by environmental factors which can induce constraints on respiratory chain components. Nutrient availability as well as oxygen pressure can both modulate mitochondrial ROS production. When moderately produced, ROS specifically regulate intracellular signalling pathways by reversible oxidation of proteins such as transcription factors or proteins kinases. In this way, they can trigger cell adaptation to environmental changes as modifications of energetic metabolism or hypoxia. Indeed, we demonstrated that mitochondrial ROS act as key elements in the control of white adipose tissue development by specific up-regulation of the anti-adipogenic transcription factor CHOP-10/GADD153. However, when they are produced at high level and in a chronic manner, mitochondrial ROS can also have deleterious effects by massive and irreversible oxidation of their principals targets i.e. lipids, DNA and proteins. In these conditions, mitochondrial ROS are involved in aging process and in pathological situations as metabolic disease

Culture and Use of Mesenchymal Stromal Cells in Phase I and II Clinical Trials

Present in numerous tissues, mesenchymal stem cells/multipotent stromal cells (MSCs) can differentiate into different cell types from a mesoderm origin. Their potential has been extended to pluripotency, by their possibility of differentiating into tissues and cells of nonmesodermic origin. Through the release of cytokines, growth factors and biologically active molecules, MSCs exert important paracrine effects during tissue repair and inflammation. Moreover, MSCs have immunosuppressive properties related to non-HLA restricted immunosuppressive capacities. All these features lead to an increasing range of possible applications of MSCs, from treating immunological diseases to tissue and organ repair, that should be tested in phase I and II clinical trials. The most widely used MSCs are cultured from bone marrow or adipose tissue. For clinical trial implementation, BM MSCs and ADSCs should be produced according to Good Manufacturing Practices. Safety remains the major concern and must be ensured during culture and validated with relevant controls. We describe some applications of MSCs in clinical trials

Fiber crosslinking drives the emergence of order in a 3D dynamical network model

The Extra-Cellular-Matrix (ECM) is a complex interconnected 3D network that provides structural support for the cells and tissues and defines organ architecture key for their healthy functioning. However, the intimate mechanisms by which ECM acquire their 3D architecture are still largely unknown. In this paper, we address this question by means of a 3D individual based model of interacting fibers able to spontaneously crosslink or unlink to each other and align at the crosslinks. We show that such systems are able to spontaneously generate different types of architectures. We provide a thorough analysis of the emerging structures by an exhaustive parametric analysis and the use of appropriate visualization tools and quantifiers in 3D. The most striking result is that the emergence of ordered structures can be fully explained by a single emerging variable : the proportion of crosslinks in the network. This simple variable becomes an important putative target to control and predict the structuring of biological tissues, to suggest possible new therapeutic strategies to restore tissue functions after disruption, and to help in the development of collagen-based scaffolds for tissue engineering. Moreover, the model reveals that the emergence of architecture is a spatially homogeneous process following a unique evolutionary path, and highlights the essential role of dynamical crosslinking in tissue structuring.Comment: 28 pages, 12 figures, 2 table

Spontaneous Cardiomyocyte Differentiation From Adipose Tissue Stroma Cells

Cardiomyocyte regeneration is limited in adult life. Thus, the identification of a putative source of cardiomyocyte progenitors is of great interest to provide a usable model in vitro and new perspective in regenerative therapy. As adipose tissues were recently demonstrated to contain pluripotent stem cells, the emergence of cardiomyocyte phenotype from adipose-derived cells was investigated. We demonstrated that rare beating cells with cardiomyocyte features could be identified after culture of adipose stroma cells without addition of 5-azacytidine. The cardiomyocyte phenotype was first identified by morphological observation, confirmed with expression of specific cardiac markers, immunocytochemistry staining, and ultrastructural analysis, revealing the presence of ventricle- and atrial-like cells. Electrophysiological studies performed on early culture revealed a pacemaker activity of the cells. Finally, functional studies showed that adrenergic agonist stimulated the beating rate whereas cholinergic agonist decreased it. Taken together, this study demonstrated that functional cardiomyocyte- like cells could be directly obtained from adipose tissue. According to the large amount of this tissue in adult mammal, it could represent a useful source of cardiomyocyte progenitors.Garcia Verdugo, Jose Manuel, [email protected]

Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion

OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion

Biological validation of coenzyme Q redox state by HPLC-EC measurement: relationship between coenzyme Q redox state and coenzyme Q content in rat tissues

AbstractThe properties of coenzymes Q (CoQ9 and CoQ10) are closely linked to their redox state (CoQox/total CoQ)×100. In this work, CoQ redox state was biologically validated by high performance liquid chromatography-electrochemical measurement after modulation of mitochondrial electron flow of cultured cells by molecules increasing (rotenone, carbonyl cyanide chlorophenylhydrazone) or decreasing (antimycin) CoQ oxidation. The tissue specificity of CoQ redox state and content were investigated in control and hypoxic rats. In control rats, there was a strong negative linear regression between tissular CoQ redox state and CoQ content. Hypoxia increased CoQ9 redox state and decreased CoQ9 content in a negative linear relationship in the different tissues, except the heart and lung. This result demonstrates that, under conditions of mitochondrial impairment, CoQ redox control is tissue-specific