Correlation between alteration of MFAP5 level and improvement of clinical indicators in patients with overweight polycystic ovary syndrome treated with metformin combined with liraglutide

Weixin LI; Xing LI; Mingyu LIAO; Liu SHI; Yuling ZHANG; Guiliang PENG; Pian HONG; Min LONG; Hongting ZHENG

doi:10.16016/j.2097-0927.202109129

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Correlation between alteration of MFAP5 level and improvement of clinical indicators in patients with overweight polycystic ovary syndrome treated with metformin combined with liraglutide

Clinical Medicine | 更新时间：2026-01-09

- Correlation between alteration of MFAP5 level and improvement of clinical indicators in patients with overweight polycystic ovary syndrome treated with metformin combined with liraglutide
- Journal of Army Medical University Vol. 44, Issue 3, Pages: 217-223(2022)
- 作者机构：
  
  1.400037重庆，陆军军医大学(第三军医大学)第二附属医院内分泌科
  2.210002 南京，南京大学医学院附属金陵医院内分泌科
- 作者简介：
- 基金信息：
  
  the "Clinical Medical Scientific Research Talents"Project of Xinqiao Hospital(2019XLC3021)
- DOI：10.16016/j.2097-0927.202109129
  CLC： R319;R71;R589
- Received：15 September 2021，
  
  Revised：2021-10-22，
  
  Published：15 February 2022
- 稿件说明：
移动端阅览
Weixin LI, Xing LI, Mingyu LIAO, et al. Correlation between alteration of MFAP5 level and improvement of clinical indicators in patients with overweight polycystic ovary syndrome treated with metformin combined with liraglutide[J]. Journal of Army Medical University, 2022, 44(3): 217-223.
DOI：

Weixin LI, Xing LI, Mingyu LIAO, et al. Correlation between alteration of MFAP5 level and improvement of clinical indicators in patients with overweight polycystic ovary syndrome treated with metformin combined with liraglutide[J]. Journal of Army Medical University, 2022, 44(3): 217-223. DOI： 10.16016/j.2097-0927.202109129.

摘要

目的

通过分析血浆微纤丝相关蛋白5(microfibrillar associated protein 5，MFAP5)水平变化与代谢指标改善的相关性，研究MFAP5在二甲双胍联合胰高血糖素样肽-1受体激动剂(glucagon-like peptide-1 receptor agonist，GLP-1RA)利拉鲁肽治疗超重多囊卵巢综合征(polycystic ovary syndrome

PCOS)患者中的潜在作用及机制。

方法

收集23例经我院二甲双胍联合利拉鲁肽方案治疗12周的超重或肥胖型PCOS患者的病历资料，根据体质指数(BMI)将受试者分为肥胖组(

=12)和超重组(

=11)2个亚组。口服盐酸二甲双胍肠溶片0.5 g，3次/d；皮下注射利拉鲁肽注射液0.6 mg

1次/d，1周后增加至1.2 mg，1次/d，最大剂量增至1.8 mg，1次/d。对比两组治疗前和治疗12周后的体格测量指标、代谢及炎症相关指标、性激素水平以及血浆MFAP5水平。

结果

经过12周的治疗，2组患者体格测量指标及糖脂代谢指标、炎症指标、性激素水平均有改善(

0.05)；相关性分析提示，所有患者血浆MFAP5水平变化值与体质量(

=0.520，

=0.011)、BMI(

=0.469，

=0.024)、腰围(

=0.634，

=0.001)、臀围(

=0.587，

=0.001)、空腹胰岛素(

=0.602，

=0.002)、甘油三酯(TG，

=0.556，

=0.002)的变化值呈正相关；亚组分析提示，超重组血浆MFAP5水平变化值与糖脂代谢相关指标的变化值呈正相关；肥胖组患者血浆MFAP5水平变化值与腰围(

=0.495，

=0.002)、臀围(

=0.508，

=0.010)、糖脂代谢相关指标、性激素水平的变化值呈正相关。

结论

超重PCOS患者血浆MFAP5水平可能与糖脂代谢的改善有关；MFAP5可能是参与二甲双胍联合利拉鲁肽治疗超重PCOS过程中的相关分子，可能作为超重PCOS治疗效果监测的可靠指标。

Abstract

Objective

To explore the role and underlying mechanism of microfibrillar associated protein 5 (MFAP5) in the treatment of overweight polycystic ovary syndrome (PCOS) with metformin combined with glucagon-like peptide-1 receptor agonist (GLP-1RA)

liraglutides

by analyzing the correlation of the molecule alteration with improvement of metabolic indexes.

Methods

Twenty-three overweight or obese PCOS patients who were treated with metformin combined with liraglutide for 12 weeks in our hospital during December 2019 and February 2021 were retrospectively enrolled. According to body mass index (BMI)

the subjects were divided into obese group (

=12) and overweight group (

=11). They were all given oral administration of metformin hydrochloride enteric-coated tablet (0.5 g

3 times/day) and subcutaneous injection of liraglutide injection (primarily

0.6 mg

once/day

and then increased to 1.2 mg

once/day

1 week later

with the maximum dose of 1.8 mg). Physical measurement indicators

metabolic and inflammatory related indicators and sex hormone levels of the 2 groups were collected before and after 12 weeks of treatment. Plasma MFAP5 level was detected by ELISA.

Results

After 12 weeks of treatment

physical measurement indicators

glucose and lipid metabolism indicators

inflammatory indicators and sex hormone levels were all improved in both groups (

0.05). Correlation analysis showed that the alteration of plasma MFAP5 level in all patients were positively correlated with the changes of body weight (

=0.520

=0.011)

BMI (

=0.469

=0.024)

waist cir

cumference (

=0.634

=0.001)

hip circumference (

=0.587

=0.001)

fasting insulin (

=0.602

=0.002) and triglyceride (

=0.556

=0.002). For the patients form the overweight group

their change of plasma MFAP5 level had a positive correlation with the changes of glucolipid metabolism related indicators

including insulin at 60 min in insulin releasing test (

=0.602

=0.002) and triglyceride (

=0.655

=0.029). In the obese group

the change of plasma MFAP5 level was positively correlated with the changes of waist circumference (

=0.495

=0.002)

hip circumference (

=0.508

=0.010)

glucolipid metabolism related indicators

such as fasting insulin (

=0.578

=0.001)

insulin at 180 min (

=0.656

=0.021)

HOMA-IR (

=0.497

=0.012)

triglyceride (

=0.595

=0.041)

and sex hormone.

Conclusion

In overweight PCOS patients

plasma MFAP5 level is related to the improvement of glucolipid metabolism. MFAP5 may be a related molecule involved in the treatment of overweight PCOS with liraylutide combined with metformin

and may serve as a reliable indicator in monitoring of therapeutic efficacy.

关键词

Keywords

references

JOHAM A E, PALOMBA S, HART R. Polycystic ovary syndrome, obesity, and pregnancy[J]. Semin Reprod Med, 2016, 34(2): 93-101. DOI: 10.1055/s-0035-1571195.

MARCH W A, MOORE V M, WILLSON K J, et al . The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria[J ] . Hum Reprod, 2010, 25(2): 544-551. DOI: 10.1093/humrep/dep399.

CHANTRAPANICHKUL P, INDHAVIVADHANA S, WONGWANANURUK T, et al . Prevalence of type 2 diabetes mellitus compared between lean and overweight/obese patients with polycystic ovarian syndrome: a 5-year follow-up study[J ] . Arch Gynecol Obstet, 2020, 301(3): 809-816. DOI: 10.1007/s00404-019-05423-2.

LIM S S, DAVIES M J, NORMAN R J, et al . Overweight, obesity and central obesity in women with polycystic ovary syndrome: a systematic review and meta-analysis[J ] . Hum Reprod Update, 2012, 18(6): 618-637. DOI: 10.1093/humupd/dms030.

NADERPOOR N, SHORAKAE S, JOHAM A, et al . Obesity and polycystic ovary syndrome[J ] . Minerva Endocrinol, 2015, 40(1): 37-51.

SHPAKOV A O. Improvement effect of metformin on female and male reproduction in endocrine pathologies and its mechanisms[J]. Pharmaceuticals, 2021, 14(1): 42. DOI: 10.3390/ph14010042.

LEGRO R S, ARSLANIAN S A, EHRMANN D A, et al . Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline[J ] . J Clin Endocrinol Metab, 2013, 98(12): 4565-4592. DOI: 10.1210/jc.2013-2350.

LAMOS E M, MALEK R, DAVIS S N. GLP-1 receptor agonists in the treatment of polycystic ovary syndrome[J]. Expert Rev Clin Pharmacol, 2017, 10(4): 401-408. DOI: 10.1080/17512433.2017.1292125.

LEMAIRE R, BAYLE J, MECHAM R P, et al . Microfibril-associated MAGP-2 stimulates elastic fiber assembly[J ] . J Biol Chem, 2007, 282(1): 800-808. DOI: 10.1074/jbc.m609692200.

LEMAIRE R, KORN J H, SHIPLEY J M, et al . Increased expression of type Ⅰ collagen induced by microfibril-associated glycoprotein 2: novel mechanistic insights into the molecular basis of dermal fibrosis in Scleroderma [J ] . Arthritis Rheum, 2005, 52(6): 1812-1823. DOI: 10.1002/art.21059..

ALBIG A R, BECENTI D J, ROY T G, et al . Microfibril-associate glycoprotein-2 (MAGP-2) promotes angiogenic cel l sprouting by blocking notch signaling in endothelial cells[J ] . Microvasc Res, 2008, 76(1): 7-14. DOI: 10.1016/j.mvr.2008.01.001.

VAITTINEN M, KOLEHMAINEN M, SCHWAB U, et al . Microfibrillar-associated protein 5 is linked with markers of obesity-related extracellular matrix remodeling and inflammation[J ] . Nutr Diabetes, 2011, 1: e15. DOI: 10.1038/nutd.2011.10.

HENEGAR C, TORDJMAN J, ACHARD V, et al . Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity[J ] . Genome Biol, 2008, 9(1): R14. DOI: 10.1186/gb-2008-9-1-r14.

KHAN T, MUISE E S, IYENGAR P, et al . Metabolic dysregulation and adipose tissue fibrosis: role of collagen Ⅵ[J ] . Mol Cell Biol, 2009, 29(6): 1575-1591. DOI: 10.1128/MCB.01300-08.

CRAFT C S, BROEKELMANN T J, MECHAM R P. Microfibril-associated glycoproteins MAGP-1 and MAGP-2 in disease[J]. Matrix Biol, 2018, 71/72: 100-111. DOI: 10.1016/j.matbio.2018.03.006.

ROTTERDAM ESHRE/ASRM-SPONSORED PCOS CONSENSUS WORKSHOP GROUP. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)[J]. Hum Reprod, 2004, 19(1): 41-47. DOI: 10.1093/humrep/deh098.

CHINA WORKING GROUP ON OBESITY. Guidelines for prevention and control of overweight and obesity in Chinese adults[J]. Acta Nutr Sin, 2004, 26(1): 1-4.

ANDERSEN A, LUND A, KNOP F K, et al . Glucagon-like peptide 1 in health and disease[J ] . Nat Rev Endocrinol, 2018, 14(7): 390-403. DOI: 10.1038/s41574-018-0016-2.

HOMBURG R. The management of infertility associated with polycystic ovary syndrome[J]. Reprod Biol Endocrinol, 2003, 1: 109. DOI: 10.1186/1477-7827-1-109.

MORAN L J, PASQUALI R, TEEDE H J, et al . Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society[J ] . Fertil Steril, 2009, 92(6): 1966-1982. DOI: 10.1016/j.fertnstert.2008.09.018.

NIAFAR M, POURAFKARI L, PORHOMAYON J, et al . A systematic review of GLP-1 agonists on the metabolic syndrome in women with polycystic ovaries[J ] . Arch Gynecol Obstet, 2016, 293(3): 509-515. DOI: 10.1007/s00404-015-3976-7.

VAITTINEN M, KOLEHMAINEN M, RYDÉN M, et al . MFAP5 is related to obesity-associated adipose tissueand extracellular matrix remodeling and inflammation[J ] . Obesity (Silver Spring), 2015, 23(7): 1371-1378. DOI: 10.1002/oby.21103.

CHRISTIAENS V, LIJNEN H R. Angiogenesis and development of adipose tissue[J]. Mol Cell Endocrinol, 2010, 318(1/2): 2-9. DOI: 10.1016/j.mce.2009.08.006.

POLAK K, CZYZYK A, SIMONCINI T, et al . New markers of insulin resistance in polycystic ovary syndrome[J ] . J Endocrinol Invest, 2017, 40(1): 1-8. DOI: 10.1007/s40618-016-0523-8.

CRAFT C S, PIETKA T A, SCHAPPE T, et al . The extracellular matrix protein MAGP1 supports thermogenesis and protects against obesity and diabetes through regulation of TGF-β[J ] . Diabetes, 2014, 63(6): 1920-1932. DOI: 10.2337/db13-1604.

MILWID J M, ELMAN J S, LI M, et al . Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators[J ] . Mol Ther, 2014, 22(5): 999-1007. DOI: 10.1038/mt.2014.17.

MANCINI A, BRUNO C, VERGANI E, et al . Oxidative stress and low-grade inflammation in polycystic ovary syndrome: controversies and new insights[J ] . Int J Mol Sci, 2021, 22(4): 1667. DOI: 10.3390/ijms22041667.

MOORE AM, CAMPBELL R E. Polycystic ovary syndrome: Understanding the role of the brain[J]. Front Neuroendocrinol, 2017, 46: 1-14. DOI: 10.1016/j.yfrne.2017.05.002.

ROTH L W, ALLSHOUSE A A, BRADSHAW-PIERCE E L, et al . Luteal phase dynamics of follicle-stimulating and luteinizing hormones in obese and normal weight women[J ] . Clin Endocrinol (Oxf), 2014, 81(3): 418-425. DOI: 10.1111/cen.12441.

GLUECK CJ, GOLDENBERG N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics[J]. Metabolism, 2019, 92: 108-120. DOI:10.1016/j.metabol.2018.11.002.

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