The anti-atherogenic aspect of metformin treatment in insulin resistant women with the polycystic ovary syndrome: Role of the newly established pro-inflammatory adipokine Acute-phase Serum Amyloid A; evidence of an adipose tissue-monocyte axis

被引:19
作者
Tan, Bee K. [1 ,2 ]
Adya, Raghu [1 ]
Shan, Xiaoye [1 ]
Aghilla, Mohamed [1 ]
Lehnert, Hendrik [1 ,3 ]
Keay, Stephen D. [1 ]
Randeva, Harpal S. [1 ]
机构
[1] Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
[2] Cambridge Univ Hosp NHS Fdn Trust, Dept Reprod Med & Surg, Addenbrookes Hosp, Cambridge CB2 0QQ, England
[3] Univ Lubeck, Sch Med, Dept Med 1, Lubeck, Germany
关键词
Adipokine; Atherosclerosis; Inflammation; Insulin resistance; Metformin; PCOS; Serum amyloid A; CARDIOVASCULAR RISK; EXPRESSION; OBESITY; FAT; MECHANISM; IMPACT; ALPHA; THP-1;
D O I
10.1016/j.atherosclerosis.2010.08.069
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Acute-phase Serum Amyloid A (ASAA) is a novel pro-inflammatory adipokine, increased in obese, insulin resistant subjects. Polycystic ovary syndrome (PCOS) is associated with inflammation and atherosclerosis. We assessed sera, adipose tissue (AT) mRNA and protein levels of ASAA of PCOS women and matched controls. Ex vivo regulation of AT ASAA by D-glucose, effects of metformin treatment on circulating ASAA in PCOS subjects and effects of sera from normal and PCOS subjects (before and after metformin) on ASAA production (THP-1 macrophages) were also studied. Methods and results: Circulating ASAA (ELISA), subcutaneous and omental AT ASAA mRNA (RT-PCR) and protein (western blotting) were significantly higher in PCOS women (P < 0.05). In AT explants, glucose significantly increased ASAA production and secretion (P < 0.05, P < 0.01). Furthermore, ASAA production (THP-1 macrophages) was significantly greater by sera from PCOS women compared to controls (P < 0.01). ASAA protein production was significantly decreased by sera from PCOS women following 6 months of metformin treatment (P < 0.05). After 6 months of metformin treatment, there was a significant decrease in circulating ASAA (P < 0.05). Importantly, changes in intima media thickness were predictive of changes in circulating ASAA (P=0.034). Conclusion: Serum and AT ASAA are increased in PCOS women and are elevated by glucose. Metformin treatment decreases serum ASAA in these women. An adipose tissue-monocyte axis may be pivotal in the pathogenesis of inflammation and atherosclerosis. ASAA may be a valuable diagnostic marker in the management of dysmetabolic states including PCOS. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:402 / 408
页数:7
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