regulation of serum amyloid a3 (saa3) in mouse colonic epithelium and adipose tissue by the intestinal microbiota调节血清淀粉样蛋白a3(saa3)在小鼠结肠上皮细胞和脂肪组织的肠道微生物群.pdfVIP

Regulation of Serum Amyloid A3 (SAA3) in Mouse Colonic Epithelium and Adipose Tissue by the Intestinal Microbiota 1,2 ¨ ´ 1,2 1,2 ¨ 1,2 Christopher S. Reigstad , Gunnel Ostergren Lunden , Jenny Felin , Fredrik Backhed * 1 Sahlgrenska Center for Cardiovascular and Metabolic Research/Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden, 2 Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden Abstract The gut microbiota has been proposed as an environmental factor that affects the development of metabolic and inflammatory diseases in mammals. Recent reports indicate that gut bacteria-derived lipopolysaccharide (LPS) can initiate obesity and insulin resistance in mice; however, the molecular interactions responsible for microbial regulation of host metabolism and mediators of inflammation have not been studied in detail. Hepatic serum amyloid A (SAA) proteins are markers and proposed mediators of inflammation that exhibit increased levels in serum of insulin-resistant mice. Adipose tissue-derived SAA3 displays monocyte chemotactic activity and may play a role in metabolic inflammation associated with obesity and insulin resistance. To investigate a potential mechanistic link between the intestinal microbiota and induction of proinflammatory host factors, we performed molecular analyses of germ-free, conventionally raised and genetically modified Myd88 2/ 2 mouse models. SAA3 expression was determined to be significantly augmented in adipose (9.961.9- fold; P,0.001) and colonic tissue (7.0 62.3-fold; P,0.05) by the presence of intestinal microbes.