This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anorexia Nervosa (AN) is a common eating disorder characterized by an extreme loss of weight. Anorexia nervosa is a common condition and is estimated to affect more than 1% of all children, adolesents and young adults. Ten percent of patients with anorexia nervosa will pursue a chronic, unremitting course, and 10% will eventually die from the disease. The mortality rate in people with anorexia nervosa is more than 12 times as high as the mortality rate in the general population. Death is often caused by cardiac arrhythmias, precipitated by diminshed heart muscle mass and electrolyte abnormalities. Ther is an increased risk of metabolic disease and death associated with AN, the prevalence of which is increasing in this country. The metabolic and inflammatory aspects of AN are not known. The purpose if this study is to fill this gap and provide a better understanding of the pathogenesis of this condition. We will determine the effects of severe weight loss and weight regain in patients with anorexia nervosa on: 1. Lipoprotein metabolism: VLDL-triglyceride (TG) and VLDL-apolipoprotein B (apoB) synthetic rates. 2. Liver protein synthetic function: retinol binding protein synthetic rate and albumin synthetic rate. 3. Markers of inflammation: Plasma C-reactive protein (CRP) concentrations, plasma cytokine concentrations, plasma fibrinogen concentration, fibrinogen fractional synthetic rates (FSR) and monocyte cytokine production. 4. Body composition and regional fat distribution: fat mass and fat-free mass, intra-abdominal and abdominal subcutaneous fat masses, and intra-hepatic lipid content. 5. Basal substrate metabolism: glucose production (glucose rate of appearance in plasma [Ra]), glucose disposal (glucose rate of disappearance in plasma [Rd]) and lipolysis [FFA Ra and glycerol Ra]. We will evaluate these specific aims by infusing stable isotope labeled tracers to measure VLDL-TG, apoB FSR, albumin FSR, fibrinogen FSR, inflammatory markers and cytokine response to peripheral blood mononuclear cells (PBMC) stimulated by lipopolysaccharide (Samonella typhimurium). Total body fat and fat-free mass will be determined by dual energy x-ray absorptiometry (DXA). Abdominal (subcutaneous and intra abdominal) adipose tissue mass will be quantified by magnetic resonance imaging (MRI) and intra-hepatic lipid content will be measured with magnetic resonance spectroscopy (MRS). Stable isotope labeled tracers will be used to measure basal substrate lipoprotein kinetics
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