Effects of a high-fat diet on energy metabolism and ROS production in rat liver.
International audience; BACKGROUND & AIMS: A high-fat diet affects liver metabolism, leading to steatosis, a complex disorder related to insulin resistance and mitochondrial alterations. Steatosis is still poorly understood since diverse effects have been reported, depending on the different experimental models used. METHODS: We hereby report the effects of an 8 week high-fat diet on liver energy metabolism in a rat model, investigated in both isolated mitochondria and hepatocytes. RESULTS: Liver mass was unchanged but lipid content and composition were markedly affected. State-3 mitochondrial oxidative phosphorylation was inhibited, contrasting with unaffected cytochrome content. Oxidative…
Preconditioning by Mitochondrial Reactive Oxygen Species Improves the Proangiogenic Potential of Adipose-Derived Cells-Based Therapy
Objective— Transplantation of adipose-derived stroma cells (ADSCs) stimulates neovascularization after experimental ischemic injury. ADSC proangiogenic potential is likely mediated by their ability to differentiate into endothelial cells and produce a wide array of angiogenic and antiapoptotic factors. Mitochondrial reactive oxygen species (ROS) have been shown to control ADSC differentiation. We therefore hypothesized that mitochondrial ROS production may change the ADSC proangiogenic properties. Methods and Results— The use of pharmacological strategies (mitochondrial inhibitors, antimycin, and rotenone, with or without antioxidants) allowed us to specifically and precisely modulate mito…
Evaluation of whole antioxidant defenses of human mononuclear cells by a new in vitro biological test: lack of correlation between erythrocyte and mononuclear cell resistance to oxidative stress
1873-2933 (Electronic) Journal Article; OBJECTIVES: This work aims to evaluate the resistance of mononuclear cells to oxidative stress using a "KRL" test, formerly utilized to evaluate the resistance of erythrocyte to free radicals. METHODS: The "KRL" test evaluates the resistance to lysis of cells treated by free radicals generated under standardized conditions. RESULTS: We defined new analytical parameters (level of radical production, time course, number of cells) to obtain an accurate assay determining the resistance to oxidative stress of mononuclear cells, in comparison to that of erythrocytes. This test allows the evaluation of change in the redox state of mononuclear cells (improved…
Insulin differently modulates hypothalamic mitochondrial energy metabolism in fed or fasted mice: Involvement in food intake regulation?
0195-6663 doi: DOI: 10.1016/j.appet.2008.04.119; In hypothalamus, mitochondria have been demonstrated to be involved in nutrients sensing but little is known concerning a mitochondrial insulin effect. The aim of our studywas thus to determine, in mice, whether (i) insulin may modulate mitochondrial functions and (ii) this effect varies according to metabolic state. O2 consumption, measured by oxygraphy in fresh hypothalamus explants was similar in fed and fasted mice on glutamate whereas it was lower in fasted mice on succinate. Whatever the metabolic state of the mice, insulin (3 nM) increased O2 consumption with glutamate. By contrast, insulin increased O2 consumption with succinate only …
Enhanced Hypothalamic Glucose Sensing in Obesity: Alteration of Redox Signalling
1939-327X (Electronic) Journal article; Objective : Recent data demonstrate that glucose sensing in different tissues is initiated by an intracellular redox-signaling pathway in physiological conditions. However, the relevance of such a mechanism in metabolic disease is not known. The aim of the present study was to determine whether brain-glucose hypersensitivity present in obese Zucker rat is related to an alteration in redox signaling. Research design and Methods: Brain glucose sensing alteration was investigated in vivo through the evaluation of electrical activity in arcuate nucleus, changes in ROS levels, and hypothalamic glucose-induced insulin secretion. In basal conditions, modific…
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. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase …
Role for mitochondrial reactive oxygen species in brain lipid sensing: redox regulation of food intake.
0012-1797 (Print) Journal Article Research Support, Non-U.S. Gov't; The ability for the brain to sense peripheral fuel availability is mainly accomplished within the hypothalamus, which detects ongoing systemic nutrients and adjusts food intake and peripheral metabolism as needed. Here, we hypothesized that mitochondrial reactive oxygen species (ROS) could trigger sensing of nutrients within the hypothalamus. For this purpose, we induced acute hypertriglyceridemia in rats and examined the function of mitochondria in the hypothalamus. Hypertriglyceridemia led to a rapid increase in the mitochondrial respiration in the ventral hypothalamus together with a transient production of ROS. Cerebral…
Hypothalamic reactive oxygen species are required for insulin-induced food intake inhibition: an NADPH oxidase-dependent mechanism
1939-327X (Electronic) Journal Article Research Support, Non-U.S. Gov't; OBJECTIVE: Insulin plays an important role in the hypothalamic control of energy balance, especially by reducing food intake. Emerging data point to a pivotal role of reactive oxygen species (ROS) in energy homeostasis regulation, but their involvement in the anorexigenic effect of insulin is unknown. Furthermore, ROS signal derived from NADPH oxidase activation is required for physiological insulin effects in peripheral cells. In this study, we investigated the involvement of hypothalamic ROS and NADPH oxidase in the feeding behavior regulation by insulin. RESEARCH DESIGN AND METHODS: We first measured hypothalamic RO…
Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 deficiency reduces leukocyte infiltration into adipose tissue and favors fat deposition
1525-2191 (Electronic) Journal Article; Obesity is associated with low-grade inflammation and leukocyte infiltration in white adipose tissue (WAT) and is linked to diabetic complications. Semicarbazide-sensitive amine oxidase, also known as vascular adhesion protein-1 (SSAO/VAP-1), is a membrane protein that is highly expressed in adipocytes and is also present on the endothelial cell surface where it is involved in leukocyte extravasation. We studied fat deposition and leukocyte infiltration in WAT of mice with a null mutation in the amine oxidase copper-containing-3 (AOC3) gene encoding SSAO/VAP-1. Both epididymal and inguinal WATs were larger in 6-month-old AOC3-KO males than in age-matc…
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, immunocy…
Method for functional study of mitochondria in rat hypothalamus
1872-678X (Electronic) Journal Article Research Support, Non-U.S. Gov't; Different roles of mitochondria in brain function according to brain area are now clearly emerging. Unfortunately, no technique is yet described to investigate mitochondria function in specific brain area. In this article, we provide a complete description of a procedure to analyze the mitochondrial function in rat brain biopsies. Our two-step method consists in a saponin permeabilization of fresh brain tissues in combination with high-resolution respirometry to acquire the integrated respiratory rate of the biopsy. In the first part, we carefully checked the mitochondria integrity after permeabilization, defined exper…
Adipose tissue sensitivity to radiation exposure
1525-2191 (Electronic) Journal Article Research Support, Non-U.S. Gov't; Treatment of cancer using radiation can be significantly compromised by the development of severe acute and late damage to normal tissue. Treatments that either reduce the risk and severity of damage or that facilitate the healing of radiation injuries are being developed, including autologous adipose tissue grafts to repair tissue defects or involutional disorders that result from tumor resection. Adipose tissue is specialized in energy storage and contains different cell types, including preadipocytes, which could be used for autologous transplantation. It has long been considered a poorly proliferative connective ti…