Obesity resulting from the delivery of an excess amount of energy to adipose tissue from glucose or free fatty acids is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) have been implicated as contributors to both the onset and the progression of insulin resistance. ROS can be generated by overloading the mitochondrial oxidative phosphorylation system, and also by nicotinamide adenine dinucleotide phosphate oxidases (NOX) produced by either adipocytes, which only produce NOX4, or by macrophages, which produce mainly NOX2. The source of the ROS might differ in the early, intermediate and late stages of obesity, switching from NOX4-dependence in the early phases to NOX2-dependence, in the intermediate phase, and transiting to mitochondria-dependence later in the time course of obesity. Thus, depending on the stage of obesity, ROS can be generated by three distinct mechanisms: i.e., NOX4, NOX2, and mitochondria. In this review, we will discuss whether NOX4-, NOX2-, and/or mitochondria-derived ROS is/are causal in the onset of adipocyte insulin resistance as obesity progresses. Moreover, we will review the pathophysiological roles of NOX4, NOX2, and mitochondria-derived ROS on adipose tissue inflammation.
Adipocytes ; Adipose Tissue* ; Fatty Acids, Nonesterified ; Glucose ; Inflammation ; Insulin Resistance* ; Insulin* ; Macrophages ; Mitochondria ; NADP ; NADPH Oxidase ; Obesity ; Oxidative Phosphorylation ; Oxidoreductases ; Reactive Oxygen Species*

Oxidized low-density lipoprotein (oxLDL) induces a wide range of cellular responses to produce atherosclerotic lesion, but key factors determining the response are not understood. In this study, purified LDL was oxidized with copper sulfate, and its physical properties and the related biological responses were investigated. The average hydrodynamic diameter of the lightly oxidized LDL was approximately 25 nm and its Rf value relative to nLDL on agarose gel was between 1.0 and 1.25. The diameter of the extensively oxidized LDL was over 30 nm, the Rf value was over 2.0. A 24 h-exposure of resting RAW264.7 macrophage cells to 100 microg/ml of the lightly oxidized LDL induced proliferation and macrophage activation whereas the extensively oxidized LDL induced cell death at the same concentration. In contrast, 200 microg/ml of oxLDL caused cell death regardless of oxidation degree. Short incubation (4-6 h) of the highly oxidized LDL (100 microg/ml) also resulted in cell proliferation. OxLDL-induced cell death showed mixed characteristics of apoptosis and/or necrosis depending on the strength and duration of the insult. These results suggest that cellular responses induced by oxLDL be dependent on the oxidation degree, the duration of exposure, and the concentration of oxLDL. Copyright 2000 Academic Press.
Animal ; Apolipoproteins B/metabolism ; Apoptosis/physiology ; Apoptosis/drug effects ; Cell Death/physiology* ; Cell Division/physiology ; Copper Sulfate/metabolism ; Dose-Response Relationship, Drug ; Human ; Lipid Peroxidation ; Lipids/metabolism ; Lipoproteins, LDL/pharmacology ; Lipoproteins, LDL/metabolism* ; Macrophages/pathology ; Macrophages/drug effects ; Macrophages/cytology* ; Mice ; Necrosis ; Oxidation-Reduction ; Thiobarbituric Acid Reactive Substances/metabolism

BACKGROUND: Lidocaine is a useful intravenous and topical adjunct to facilitate tracheal intubation. We evaluated the effect of tracheal lidocaine on tracheal intubating conditions without neuromuscular blocking agent and hemodynamics during anesthesia induction with propofol and remifentanil target-controlled infusion (TCI). METHODS: Fifty patients, aged 18-60 years, scheduled for closed reduction of fractured nasal bone were randomly assigned to the control group (n = 25) or lidocaine group (n = 25). Anesthesia was induced with propofol-remifentanil TCI with the effect-site concentration of 5 microg/ml and 5 ng/ml. Four minutes after the start of propofol-remifentanil TCI, 4% lidocaine or saline 3 ml was instilled to larynx and trachea, and intubation was performed 1 min later. Acceptable intubation was defined as excellent or good intubating conditions. Hemodynamic data, induction and recovery profiles were recorded. RESULTS: Intubating condition was clinically acceptable in 13 out of 25 (52%) patients in the control group and in 22 out of 25 (88%) in the lidocaine group, and there was a significant difference between the two groups in regard to acceptable intubating conditions (P = 0.005). Mean arterial pressure change over time was significantly different between the two groups. There were no significant differences in the heart rate between the two groups. CONCLUSIONS: This study demonstrated that laryngotracheal administration of 4% lidocaine could increase the percentage of acceptable conditions for tracheal intubation during propofol and remifentanil anesthesia without neuromuscular blockade.
Anesthesia* ; Anesthesia, Intravenous ; Arterial Pressure ; Heart Rate ; Hemodynamics ; Humans ; Intubation ; Larynx ; Lidocaine* ; Nasal Bone ; Neuromuscular Blockade* ; Piperidines ; Propofol ; Trachea