Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance

Mannerås-Holm, Louise; Leonhardt, Henrik; Kullberg, Joel; Jennische, Eva; Odén, Anders; Holm, Göran; Hellström, Mikael; Lönn, Lars; Olivecrona, Gunilla; Stener-Victorin, Elisabet; Lönn, Malin

doi:10.1210/jc.2010-1290

Cited by 294 publications

(184 citation statements)

References 41 publications

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“…Thus, we determined whether the adiponectin level is altered in the PCOS human and rat. Consistent with a previous report (28), the circulating adiponectin level was significantly decreased in both the PCOS patient and rat (Fig. S3 A and B and Table S4).…”

Section: Administration Of Adiponectin Recapitulates the Beneficial Esupporting

confidence: 92%

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

Yuan

Zhao

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

147

103

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Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS.brown adipose tissue | transplantation | ameliorates | PCOS | adiponectin

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Section: Administration Of Adiponectin Recapitulates the Beneficial Esupporting

confidence: 92%

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

Yuan

Zhao

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

147

103

View full text Add to dashboard Cite

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“…In recent years, attention has centred on determining body composition in PCOS women with different body mass index, quantity and quality of bone mass and (Zborowski et al, 2000;Kirchengast et Huber 2001;Faulds 2003;Puder et al 2005;To and Wong 2005;Toscani et al 2007;Barber et al 2008;Cosar et al 2008;Moran and Teede 2009;Kassanos et al 2010;March et al 2010;Manneras-Holm et al 2011;Villa et al 2011 andFranks 2013). Our study presents analytic results of investigations into body composition and somatotype in lean PCOS women.…”

Section: Discussionmentioning

confidence: 99%

Body composition of lean women with polycystic ovary syndrome

Zabulienė

Urbonienė

Tutkuvienė

2013

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Polycystic ovary syndrome (PCOS) is one of the most frequent endocrine and metabolic disorders in reproductive age women, and it is related to changes in body size, shape and composition. Anthropometric somatotype is a quantitative description of the individual's body shape and composition classified as endomorphy, mesomorphy or ectomorphy. Since PCOS somatotype has never previously been studied, here we evaluate body shape and composition phenomena in lean women with polycystic ovary syndrome and assess relationships with metabolic parameters. The study of 20-35 year-old women was carried out at the Department of Anatomy, Histology and Anthropology at Vilnius University. Standard anthropometric instruments and methods were used, and J. Matiegka's equations calculated skeletal mass, skin and subcutaneous adipose tissue and muscles and internal organs. In addition, Heath -Carter's somatotypes were computed, and the participants' glucose, insulin, testosterone, sex hormone-binding globulin and lipid levels were established. We analysed data from 120 women with a mean age of 27.30 ± 3.68 years. Lean women with PCOS had greater skeletal mass by 0.47 kg (p<0.05, Cohen's d=1.14), greater skin and subcutaneous adipose tissue mass by 2.79 kg (p<0.05, Cohen's d=6.07) and lower muscle mass by 1.47 kg (p<0.05, Cohen's d=2.84) compared to control women (p<0.05). The mean PCOS somatotype ratio was 4.96-4.38-3.00 (SD 1.50-1.26-1.11). This classified women with PCOS as mesomorphic endomorphs, in contrast to healthy women who were endomorphic mesomorphs. The PCOS subjects' skin and subcutaneous adipose tissue and endomorphy/mesomorphy somatotype positively correlated with insulin levels and the HOMA-IR. It was established that lean women with polycystic ovary syndrome had a mesomorphic endomorph somatotype and higher skin and subcutaneous adipose tissue mass, but less muscle mass than healthy lean women. In addition, skin and subcutaneous adipose tissue positively correlated with insulin level and HOMA-IR in lean PCOS women.

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“…Adiponectin, postulated to be a beneficial adipokine due to its insulin-sensitizing property and antiatherogenic action (40), is reduced in women with PCOS (41). Treatment with adiponectin in a rat model of PCOS ameliorates the PCOS phenotype by reversing acyclicity and PCOS ovarian features, and also improves glucose homeostasis (42).…”

Section: Discussionmentioning

confidence: 99%

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

Caldwell

Edwards

Desai

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

165

174

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Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanismbased treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype. Global loss of the AR reveals that AR signaling is required for all DHT-induced features of PCOS. Neuron-specific AR signaling was required for the development of dysfunctional ovulation, classic polycystic ovaries, reduced large antral follicle health, and several metabolic traits including obesity and dyslipidemia. In addition, ovariectomized ARKO hosts with wild-type ovary transplants displayed normal estrous cycles and corpora lutea, despite DHT treatment, implying extraovarian and not intraovarian AR actions are key loci of androgen action in generating the PCOS phenotype. These findings provide strong evidence that neuroendocrine genomic AR signaling is an important extraovarian mediator in the development of PCOS traits. Thus, targeting AR-driven mechanisms that initiate PCOS is a promising strategy for the development of novel treatments for PCOS.PCOS | androgen | animal model | neuroendocrine P olycystic ovary syndrome (PCOS) is the most frequent endocrine disorder of young women, with a prevalence of 6 to 15% (1), and accounts for more than 75% of anovulatory infertility (2). It is characterized by reproductive hormone dysregulation involving luteinizing hormone (LH) hypersecretion and hyperandrogenism (3), the consequences of which can be acne and hirsutism, as well as reduced fertility, due to aberrant follicular maturation, ovulatory disturbance, and miscarriage (3). Associated nonreproductive abnormalities, such as obesity, metabolic syndrome, hyperinsulinemia, insulin resistance, hepatic steatosis, and dyslipidemia predispose affected women to heightened risk of cardiovascular disease and type 2 diabetes (3, 4). However, despite the high prevalence and significant health impact, the pathogenesis of PCOS remains unclear so that mechanism-based treatments remain unattainable.Hyperandrogenism, the most consistent feature of PCOS (5), is implicated as a key mediator in the pathogenesis of PCOS. Supportive evidence includes that androgen excess from endogenous [congenital adrenal hyperplasia (6)] or exogenous [female-to-male transsexuals (7)] sources can produce polycystic ovaries. Furthermore, androgens induce reproductive, metabolic, and endocrine features of PCOS in rodent, sheep, and primate animal models of PCOS (8-10). As all androgen action is mediated via the androgen receptor (AR),...

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Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance

Cited by 294 publications

References 41 publications

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

Body composition of lean women with polycystic ovary syndrome

Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome

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