Electroacupuncture improves metabolic and ovarian function in a rat model of polycystic ovary syndrome by decreasing white adipose tissue,increasing brown adipose tissue,and modulating the gut microbiota

Abstract

Background:

Polycystic ovary syndrome (PCOS) affects 8%–15% of reproductive-age women and is associated with reproductive disorders, abdominal obesity, hyperinsulinemia, insulin resistance, type 2 diabetes, and cardiovascular diseases. Acupuncture, as a traditional physical therapy method, could affect various metabolic disorders such as obesity, hyperplasia, gout, and cardiovascular and cerebrovascular diseases in clinical practice. Moreover, electroacupuncture (EA) has been shown to decrease body weight in rats with PCOS; however, the mechanism of weight loss and the relationship between adipose tissue and gut microbiota remain unclear.

Objective:

To explore the effect and mechanism of EA on white and brown adipose tissues and gut microbiota, and its follow-up effect on reproductive function, in a rat model of PCOS.

Methods:

Daily EA treatment was administered at ST29 and SP6 in a dihydrotestosterone (DHT)-induced PCOS-like rat model (PCOS + EA group). Effects of EA on in vivo and in vitro adipose volume and weight, organ weight coefficients, body weight, hormonal profiles, and estrous cyclicity were measured, and compared with untreated PCOS model rats (PCOS group) and healthy rats (control group). Microbial DNA was extracted from the fecal samples to analyze group abundance and diversity.

Results:

EA improved estrous cyclicity, decreased body weight, decreased visceral and subcutaneous fat content, and increased brown adipose tissue weight. EA also normalized serum DHT and progesterone levels and improved glucose tolerance. There were few significant differences in the composition or diversity of the gut microbiota between control, PCOS, and PCOS + EA groups, except for the relative abundances of Tenericutes at the phylum level and Prevotella_9 at the genus level, which were significantly different in the PCOS group before and after EA treatment. Both are important microflora, strongly related to body weight.

Conclusion:

EA regulated the metabolic disorders and improved reproductive function in this PCOS-like rat model by adjusting visceral fat and brown fat, as well as intestinal flora.

Keywords

brown adipose tissue electroacupuncture gut microbiota polycystic ovary syndrome

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References

Goodarzi

Dumesic

Chazenbalk

, et al. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol 2011; 7(4): 219–231.

Azziz

Marin

Hoq

, et al. Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab 2005; 90(8): 4650–4658.

Hoeger

Oberfield

. Do women with PCOS have a unique predisposition to obesity? Fertil Steril 2012; 97(1): 13–17.

Diamanti-Kandarakis

Papavassiliou

Kandarakis

, et al. Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab 2007; 18(7): 280–285.

Ravussin

Galgani

. The implication of brown adipose tissue for humans. Annu Rev Nutr 2011; 31: 33–47.

Kahn

Wang

Lee

. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest 2019; 129: 3990–4000.

Yuan

Zhao

, et al. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome. Proc Natl Acad Sci U S A 2016; 113: 2708–2713.

Doretto-Silva

Steiner

Veridiano

, et al. White, brown, and bone marrow adipose tissue behavior in DHEA-induced PCOS mice. Gynecol Endocrinol 2021; 37: 15–20.

Sayin

Wahlstrom

Felin

, et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab 2013; 17: 225–235.

10.

Jones

Tomaro-Duchesneau

Prakash

. The gut microbiome, probiotics, bile acids axis, and human health. Trends Microbiol 2014; 22(6): 306–308.

11.

Wei

Huang

Zhao

, et al. A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility. EBioMedicine 2020; 55: 102766.

12.

Broeders

Nascimento

Havekes

, et al. The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab 2015; 22: 418–426.

13.

Torres

Siakowska

Banaszewska

, et al. Gut microbial diversity in women with polycystic ovary syndrome correlates with hyperandrogenism. J Clin Endocrinol Metab 2018; 103: 1502–1511.

14.

Sherman

Sarsour

Salehi

, et al. Prenatal androgen exposure causes hypertension and gut microbiota dysbiosis. Gut Microbes 2018; 9(5): 400–421.

15.

Yun

Sun

, et al. Gut microbiota-bile acid-interleukin-22 axis orchestrates polycystic ovary syndrome. Nat Med 2019; 25(8): 1225–1233. Erratum in: Nat Med 2019; 25(9): 1459.

16.

Martinez

Peplow

. Treatment of insulin resistance by acupuncture: a review of human and animal studies. Acupunct Med 2016; 34(4): 310–319.

17.

Smith

Armour

. Complementary therapies and medicines and reproductive medicine. Semin Reprod Med 2016; 34(2): 67–73.

18.

Miao

, et al. Regulating gut flora dysbiosis in obese mice by electroacupuncture. Am J Chin Med. Epub ahead of print 4 October 2018. DOI: 10.1142/S0192415X18500763.

19.

Wang

Liang

, et al. Acupuncture regulating gut microbiota in abdominal obese rats induced by high-fat diet. Evid Based Complement Alternat Med 2019; 2019: 4958294.

20.

Zhang

Cui

, et al. Diversity of the gut microbiota in dihydrotestosterone-induced PCOS rats and the pharmacologic effects of diane-35, probiotics, and berberine. Front Microbiol 2019; 10: 175.

21.

Marcondes

Bianchi

Tanno

. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 2002; 62(4A): 609–614.

22.

Qian

Huang

Tang

. Brown and beige fat: the metabolic function, induction, and therapeutic potential. Front Med 2015; 9(2): 162–172.

23.

Sakellariou

Valente

Carrillo

, et al. Chronic l-menthol-induced browning of white adipose tissue hypothesis: a putative therapeutic regime for combating obesity and improving metabolic health. Med Hypotheses 2016; 93: 21–26.

24.

Bartelt

Heeren

. Adipose tissue browning and metabolic health. Nat Rev Endocrinol 2014; 10: 24–36.

25.

Mestdagh

Dumas

Rezzi

, et al. Gut microbiota modulate the metabolism of brown adipose tissue in mice. J Proteome Res 2012; 11: 620–630.

26.

Suárez-Zamorano

Fabbiano

Chevalier

, et al. Microbiota depletion promotes browning of white adipose tissue and reduces obesity. Nat Med 2015; 21(12): 1497–1501.

27.

Shen

Wang

, et al. Acupuncture promotes white adipose tissue browning by inducing UCP1 expression on DIO mice. BMC Complement Altern Med 2014; 14: 501.

28.

Zhou

Wang

Shu

, et al. Effect of “biao-ben points association” electroacupuncture combined with dietary restriction on SIRT1 and UCP1 expression in brown adipose tissue of obese rats. World Chinese Journal of Digestology 2016; 24(22): 3410–3416.

29.

Lindheim

Bashir

Münzker

, et al. Alterations in gut microbiome composition and barrier function are associated with reproductive and metabolic defects in women with polycystic ovary syndrome (PCOS): a pilot study. PLoS ONE 2017; 12(1): e0168390.

30.

Bliss

Whiteside

. The gut-brain axis, the human gut microbiota and their integration in the development of obesity. Front Physiol 2018; 9: 900.

31.

El Aidy

Dinan

Cryan

. Gut microbiota: the conductor in the orchestra of immune-neuroendocrine communication. Clin Ther 2015; 37: 954–967.

32.

Tian

Wang

, et al. Up-regulation of the expression of cocaine and amphetamine-regulated transcript peptide by electroacupuncture in the arcuate nucleus of diet-induced obese rats. Neurosci Lett 2005; 383: 17–21.

33.

, et al. Acupuncture and regulation of gastrointestinal function. World J Gastroenterol 2015; 21: 8304–8313.

34.

Wahlstrom

Sayin

Marschall

, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metab 2016; 24: 41–50.

35.

Worthmann

John

Rühlemann

, et al. Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nat Med 2017; 23(7): 839–849.

36.

Scher

Sczesnak

Longman

, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife 2013; 2: e01202.

37.

Chen

Hoffmann

, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science 2011; 334: 105–108.

38.

De Filippo

Cavalieri

Di Paola

, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A 2010; 107: 14691–14696.

39.

Yatsunenko

Rey

Manary

, et al. Human gut microbiome viewed across age and geography. Nature 2012; 486: 222–227.

40.

Dillon

Lee

Kotter

, et al. Gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection. Mucosal Immunol 2016; 9(1): 24–37.

41.

Oakley

Fiedler

Marrazzo

, et al. Diversity of human vaginal bacterial communities and associations with clinically defined bacterial vaginosis. Appl Environ Microbiol 2008; 74(15): 4898–4909.

42.

Brook

. Microbiology and antimicrobial management of sinusitis. J Laryngol Otol 2005; 119: 251–258.

43.

Teles

Uzel

, et al. Early microbial succession in redeveloping dental biofilms in periodontal health and disease. J Periodontal Res 2012; 47(1): 95–104.

44.

Umeda

Chen

Bakker

, et al. Risk indicators for harboring periodontal pathogens. J Periodontol 1998; 69(10): 1111–1118.

45.

Akcalı

Bostanci

Özçaka

, et al. Association between polycystic ovary syndrome, oral microbiota and systemic antibody responses. PLoS ONE 2014; 9(9): e108074.

46.

Kelley

Skarra

Rivera

, et al. The gut microbiome is altered in a letrozole-induced mouse model of polycystic ovary syndrome. PLoS ONE 2016; 11(1): e0146509.