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
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作者:
Tan, Bee K.
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Cambridge Univ Hosp NHS Fdn Trust, Dept Reprod Med & Surg, Addenbrookes Hosp, Cambridge CB2 0QQ, EnglandUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Tan, Bee K.
[1
,2
]
Adya, Raghu
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, EnglandUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Adya, Raghu
[1
]
Shan, Xiaoye
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, EnglandUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Shan, Xiaoye
[1
]
Aghilla, Mohamed
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, EnglandUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Aghilla, Mohamed
[1
]
Lehnert, Hendrik
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Univ Lubeck, Sch Med, Dept Med 1, Lubeck, GermanyUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Lehnert, Hendrik
[1
,3
]
Keay, Stephen D.
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, EnglandUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
Keay, Stephen D.
[1
]
Randeva, Harpal S.
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Univ Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, EnglandUniv Warwick, Endocrinol & Metab Grp, Clin Sci Res Inst, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England
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
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.
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Univ Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Dasu, Mohan R.
Devaraj, Sridevi
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Univ Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Devaraj, Sridevi
Zhao, Ling
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Univ Calif Davis, Davis, CA 95616 USA
ARS, USDA, Western Human Nutr Res Ctr, Davis, CA USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Zhao, Ling
Hwang, Daniel H.
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Univ Calif Davis, Davis, CA 95616 USA
ARS, USDA, Western Human Nutr Res Ctr, Davis, CA USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Hwang, Daniel H.
Jialal, Ishwarlal
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Univ Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
机构:
PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, HERSHEY, PA 17033 USAPENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, HERSHEY, PA 17033 USA
机构:
Univ Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Dasu, Mohan R.
Devaraj, Sridevi
论文数: 0引用数: 0
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机构:
Univ Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Devaraj, Sridevi
Zhao, Ling
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Davis, Davis, CA 95616 USA
ARS, USDA, Western Human Nutr Res Ctr, Davis, CA USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Zhao, Ling
Hwang, Daniel H.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Davis, Davis, CA 95616 USA
ARS, USDA, Western Human Nutr Res Ctr, Davis, CA USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
Hwang, Daniel H.
Jialal, Ishwarlal
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USAUniv Calif Davis, Med Ctr, Lab Atherosclerosis & Metab Res, Sacramento, CA 95817 USA
机构:
PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, HERSHEY, PA 17033 USAPENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, HERSHEY, PA 17033 USA