Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications

• Published in: PLoS medicine Vol. 3; no. 6; p. e287
• Main Authors: Yang, Rong-Ze, Lee, Mi-Jeong, Hu, Hong, Pollin, Toni I, Ryan, Alice S, Nicklas, Barbara J, Snitker, Soren, Horenstein, Richard B, Hull, Kristen, Goldberg, Nelson H, Goldberg, Andrew P, Shuldiner, Alan R, Fried, Susan K, Gong, Da-Wei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2006; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipocytes - drug effects; Adipocytes - metabolism; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Biomarkers - metabolism; Body fat; Body mass index; Cardiology/Cardiac Surgery; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cardiovascular Diseases - metabolism; Cardiovascular Medicine; Cell Line; Clinical Trials as Topic; Cross-Sectional Studies; Cytokines; Cytokines - metabolism; Diabetes; Diabetes/Endocrinology/Metabolism; Dose-Response Relationship, Drug; Endocrinology; Fatty acids; Female; Heart attacks; Humans; Hypoglycemic Agents - therapeutic use; Immunology; Immunology and allergy; Inflammation; Inflammation - blood; Inflammation - complications; Inflammation - metabolism; Insulin resistance; Lipolysis - drug effects; Male; Metabolic diseases; Metabolism; Mice; Mice, Inbred C57BL; Middle Aged; Nutrition; Obesity; Obesity - blood; Obesity - complications; Obesity - drug therapy; Obesity - metabolism; Obesity - therapy; Proteins; Risk Factors; RNA, Messenger - metabolism; Rosiglitazone; Serum Amyloid A Protein - genetics; Serum Amyloid A Protein - metabolism; Serum Amyloid A Protein - pharmacology; Stromal Cells - metabolism; Thiazolidinediones - therapeutic use; Tumor necrosis factor-TNF; Weight control; United States > US; Cardiovascular Diseases; Biological Markers; Humans; Middle Aged; Male; Adipocytes; Dose-Response Relationship, Drug; Hypoglycemic Agents; Stromal Cells; Female; Adipose Tissue; Serum Amyloid A Protein; Cell Line; Obesity; Cross-Sectional Studies; Cytokines; Mice, Inbred C57BL; Risk Factors; Clinical Trials as Topic; Inflammation; Lipolysis; Animals; Mice; RNA, Messenger; Thiazolidinediones
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.0030287

Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index (r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants (p = 0.006), as well as in those treated with rosiglitazone (p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA (r = -0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.