A Single Bout of Electroacupuncture Remodels Epigenetic and Transcriptional Changes in Adipose Tissue in Polycystic Ovary Syndrome

Overview

Journal Sci Rep

Specialty Science

Date 2018 Feb 1

PMID 29382850

Citations 26

Authors

Milana Kokosar

Anna Benrick

Alexander Perfilyev

Emma Nilsson

Thomas Kallman

Claes Ohlsson

Charlotte Ling

Elisabet Stener-Victorin

Affiliations

Soon will be listed here.

Abstract

A single bout of electroacupuncture results in muscle contractions and increased whole body glucose uptake in women with polycystic ovary syndrome (PCOS). Women with PCOS have transcriptional and epigenetic alterations in the adipose tissue and we hypothesized that electroacupuncture induces epigenetic and transcriptional changes to restore metabolic alterations. Twenty-one women with PCOS received a single bout of electroacupuncture, which increased the whole body glucose uptake. In subcutaneous adipose tissue biopsies, we identified treatment-induced expression changes of 2369 genes (Q < 0.05) and DNA methylation changes of 7055 individual genes (Q = 0.11). The largest increase in expression was observed for FOSB (2405%), and the largest decrease for LOC100128899 (54%). The most enriched pathways included Acute phase response signaling and LXR/RXR activation. The DNA methylation changes ranged from 1-16%, and 407 methylation sites correlated with gene expression. Among genes known to be differentially expressed in PCOS, electroacupuncture reversed the expression of 80 genes, including PPARγ and ADIPOR2. Changes in the expression of Nr4a2 and Junb are reversed by adrenergic blockers in rats demonstrating that changes in gene expression, in part, is due to activation of the sympathetic nervous system. In conclusion, low-frequency electroacupuncture with muscle contractions remodels epigenetic and transcriptional changes that elicit metabolic improvement.

Citing Articles

The effects of acupuncture on patients with premature ovarian insufficiency and polycystic ovary syndrome: an umbrella review of systematic reviews and meta-analyses.

Bai T, Deng X, Bi J, Ni L, Li Z, Zhuo X Front Med (Lausanne). 2024; 11:1471243.

PMID: 39655237 PMC: 11627218. DOI: 10.3389/fmed.2024.1471243.

The State of 21st Century Acupuncture in the United States.

Smith C, Reddy B, Wolf C, Schnyer R, St John K, Conboy L J Pain Res. 2024; 17:3329-3354.

PMID: 39403098 PMC: 11472758. DOI: 10.2147/JPR.S469491.

From proteome to pathogenesis: investigating polycystic ovary syndrome with Mendelian randomization analysis.

Zhang J, Li Y, Gong A, Wang J Front Endocrinol (Lausanne). 2024; 15:1442483.

PMID: 39314522 PMC: 11417002. DOI: 10.3389/fendo.2024.1442483.

Effects and mechanisms of acupuncture on women related health.

Qin H, Feng J, Wu X Front Med. 2023; 18(1):46-67.

PMID: 38151668 DOI: 10.1007/s11684-023-1051-5.

Immunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome.

Kicinska A, Maksym R, Zabielska-Kaczorowska M, Stachowska A, Babinska A Biomedicines. 2023; 11(6).

PMID: 37371662 PMC: 10295970. DOI: 10.3390/biomedicines11061567.

References

Seow K, Tsai Y, Juan C, Lin Y, Hwang J, Ho L . Omental fat expression of adiponectin and adiponectin receptors in non-obese women with PCOS: a preliminary study. Reprod Biomed Online. 2009; 19(4):577-82. DOI: 10.1016/j.rbmo.2009.05.003. View

Johnson W, Li C, Rabinovic A . Adjusting batch effects in microarray expression data using empirical Bayes methods. Biostatistics. 2006; 8(1):118-27. DOI: 10.1093/biostatistics/kxj037. View

Coviello A, Sam S, Legro R, Dunaif A . High prevalence of metabolic syndrome in first-degree male relatives of women with polycystic ovary syndrome is related to high rates of obesity. J Clin Endocrinol Metab. 2009; 94(11):4361-6. PMC: 2775643. DOI: 10.1210/jc.2009-1333. View

Kucuk E, Bindayi A, Boylu U, Onol F, Gumus E . Randomised clinical trial of comparing effects of acupuncture and varicocelectomy on sperm parameters in infertile varicocele patients. Andrologia. 2016; 48(10):1080-1085. DOI: 10.1111/and.12541. View

Lee K, Kim S, Cha Y, So J, Park J, Kang K . Effect of exercise on hepatic gene expression in an obese mouse model using cDNA microarrays. Obesity (Silver Spring). 2006; 14(8):1294-302. DOI: 10.1038/oby.2006.147. View

Oosterhof R, Ith M, Trepp R, Christ E, Fluck M . Regulation of whole body energy homeostasis with growth hormone replacement therapy and endurance exercise. Physiol Genomics. 2011; 43(12):739-48. DOI: 10.1152/physiolgenomics.00034.2010. View

Barres R, Yan J, Egan B, Treebak J, Rasmussen M, Fritz T . Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012; 15(3):405-11. DOI: 10.1016/j.cmet.2012.01.001. View

Kokosar M, Benrick A, Perfilyev A, Fornes R, Nilsson E, Maliqueo M . Epigenetic and Transcriptional Alterations in Human Adipose Tissue of Polycystic Ovary Syndrome. Sci Rep. 2016; 6:22883. PMC: 4791632. DOI: 10.1038/srep22883. View

Orio F, Muscogiuri G, Nese C, Palomba S, Savastano S, Tafuri D . Obesity, type 2 diabetes mellitus and cardiovascular disease risk: an uptodate in the management of polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2016; 207:214-219. DOI: 10.1016/j.ejogrb.2016.08.026. View

10.

Stener-Victorin E . Hypothetical physiological and molecular basis for the effect of acupuncture in the treatment of polycystic ovary syndrome. Mol Cell Endocrinol. 2013; 373(1-2):83-90. DOI: 10.1016/j.mce.2013.01.006. View

11.

Lin X, Han M, Cheng L, Chen J, Zhang Z, Shen T . Expression dynamics, relationships, and transcriptional regulations of diverse transcripts in mouse spermatogenic cells. RNA Biol. 2016; 13(10):1011-1024. PMC: 5056783. DOI: 10.1080/15476286.2016.1218588. View

12.

Hughes T, Giri P, de Vera I, Marciano D, Kuruvilla D, Shin Y . An alternate binding site for PPARγ ligands. Nat Commun. 2014; 5:3571. PMC: 4070320. DOI: 10.1038/ncomms4571. View

13.

Perfilyev A, Dahlman I, Gillberg L, Rosqvist F, Iggman D, Volkov P . Impact of polyunsaturated and saturated fat overfeeding on the DNA-methylation pattern in human adipose tissue: a randomized controlled trial. Am J Clin Nutr. 2017; 105(4):991-1000. DOI: 10.3945/ajcn.116.143164. View

14.

Dunaif A . Perspectives in Polycystic Ovary Syndrome: From Hair to Eternity. J Clin Endocrinol Metab. 2016; 101(3):759-68. PMC: 4803161. DOI: 10.1210/jc.2015-3780. View

15.

Kagitani F, Uchida S, Hotta H . Afferent nerve fibers and acupuncture. Auton Neurosci. 2010; 157(1-2):2-8. DOI: 10.1016/j.autneu.2010.03.004. View

16.

Puntschart A, Wey E, Jostarndt K, Vogt M, Wittwer M, Widmer H . Expression of fos and jun genes in human skeletal muscle after exercise. Am J Physiol. 1998; 274(1):C129-37. DOI: 10.1152/ajpcell.1998.274.1.C129. View

17.

Flach R, Bennett A . Mitogen-activated protein kinase phosphatase-1 - a potential therapeutic target in metabolic disease. Expert Opin Ther Targets. 2010; 14(12):1323-32. PMC: 2982191. DOI: 10.1517/14728222.2010.528395. View

18.

Comim F, Hardy K, Franks S . Adiponectin and its receptors in the ovary: further evidence for a link between obesity and hyperandrogenism in polycystic ovary syndrome. PLoS One. 2013; 8(11):e80416. PMC: 3832407. DOI: 10.1371/journal.pone.0080416. View

19.

Chazenbalk G, Chen Y, Heneidi S, Lee J, Pall M, Chen Y . Abnormal expression of genes involved in inflammation, lipid metabolism, and Wnt signaling in the adipose tissue of polycystic ovary syndrome. J Clin Endocrinol Metab. 2012; 97(5):E765-70. PMC: 3339894. DOI: 10.1210/jc.2011-2377. View

20.

Amouzou C, Breuker C, Fabre O, Bourret A, Lambert K, Birot O . Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women. PLoS One. 2016; 11(4):e0154119. PMC: 4844150. DOI: 10.1371/journal.pone.0154119. View