Tenomodulin, serum amyloid A and the serum amyloid A receptor selenoprotein S – implications for metabolic disease
نویسنده
چکیده
Obesity and obesity-related metabolic diseases are associated with a low-grade inflammation, including slightly increased serum levels of the acute phase protein serum amyloid A (A-SAA). A-SAA is one amongst several adipose tissue (AT) produced proteins suggested to influence development of metabolic diseases. The A-SAA protein may have pro-atherogenic functions, and release of A-SAA from the AT may contribute to the development of cardiovascular disease. Furthermore, A-SAA is functionally linked to insulin resistance via one of its receptors, selenoprotein S (SELS). The tenomodulin (TNMD) gene is expressed in adipose tissue, but its role in obesity is unclear. The overall aim of this thesis was to increase our understanding of how TNMD, A-SAA and SELS relate to obesity and obesity-associated metabolic diseases. An additional aim was to establish a mouse model mirroring the human A-SAA production in AT. To achieve these goals, we (1) investigated TNMD gene expression in human AT by DNA microarray and real-time PCR analysis; (2) analyzed serum levels of A-SAA in a cohort with a wide range in body mass index and metabolic parameters; (3) analyzed SELS gene expression and genotyped three SELS polymorphisms, previously associated with serum levels of inflammatory markers, in a casecontrol study of coronary heart disease and (4) generated a mouse model with transgenic overexpression of the human SAA1 (hSAA) gene in AT. The TNMD gene was highly expressed in human AT, with a higher expression in obese compared to lean subjects. Furthermore, TNMD gene expression was down-regulated during diet-induced weight loss. These data suggest that TNMD plays a role in the adipose tissue. Inflammatory markers and measures of glycemic control were strongly associated with serum levels of A-SAA. The strongest associations were found in women, and serum levels of A-SAA were associated with adipocyte size in women only. These data suggest that sex-specific factors have to be considered when analyzing serum levels of A-SAA in relation to metabolic disease. Gene expression of SELS in AT was associated with measures of obesity. Furthermore, genetic variants in the SELS gene were associated with serum levels of glucose, measures of insulin resistance and blood pressure. These findings suggest that SELS plays a role in the development of metabolic disease. In the hSAA mouse model, hSAA was specifically expressed in AT and plasma levels of hSAA were increased in obese mice. The hSAA protein was found to be co-localized to high-density lipoprotein containing fractions of plasma. In conclusion, the results of this thesis suggest that TNMD, A-SAA and SELS have metabolic effects that should be further explored. The established hSAA transgenic mouse model opens the possibility to further explore the effects of AT-derived A-SAA on cardiovascular disease. ISBN 978-91-628-8042-2 98 pages Göteborg 2010
منابع مشابه
Evaluation of serum and milk amyloid A in some inflammatory diseases of cattle
This study was designed to evaluate serum and milk amyloid A (SAA) as an inflammatory indicator in inflammatory diseases. Twenty clinically healthy cows and 100 cows with various inflammatory diseases were selected for this study. Blood samples were collected from the coccygeal vein of both healthy and diseased groups. Milk samples were taken from four quarters of both groups. Milk samples of f...
متن کاملThe Serum Amyloid β Level in Multiple Sclerosis: A Case- Control Study
Background: Multiple sclerosis (MS) is one of the most common autoimmune diseases in adults that cause disability in patients. Different studies were conducted on more rapid diagnosis of the disease such as measuring serum or cerebrospinal fluid (CSF) contents. Objectives: The current study aimed at measuring amyloid β (Aβ) serum levels in patients with relapsing-remitting MS. Mater...
متن کاملSerum concentrations of haptoglobin and serum amyloid A in water buffaloes (Bubalus bubalis) with abomasal ulcer
To evaluate the serum concentrations of haptoglobin (Hp) and serum amyloid A (SAA) in water buffaloes with abomasal ulcers, the abomasums of 100 randomly selected water buffaloes were examined after slaughter. Type I abomasal ulcers were found in 56 out of 100 buffaloes. Serum concentrations of Hp and SAA were measured. There was no significant difference between affected and non-affected buffa...
متن کاملEffectiveness of Eight Weeks Aerobic Training and Nano Curcumin Supplementation on Serum Amyloid A Protein Content and Body Composition in Overweight and Obese Women
Introduction: Serum Amyloid A (SAA) is a sensitive marker related to the acute inflammatory phase, produced in the liver, and has got the protection and repair role in the inflammatory process. Nano curcumin (turmeric pigment) is anti-inflammatory and antioxidant. The purpose of this study was to evaluate the impact of advanced aerobic training and Nano curcumin supplementation on body composit...
متن کاملEffect of ascorbic acid and alpha-tocopherol supplementations on serum leptin, tumor necrosis factor alpha, and serum amyloid A levels in individuals with type 2 diabetes mellitus
Objective: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering anti-inflammatory properties of plant extracts rich in ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), anti-diabetic properties of these two well-known anti...
متن کامل