Serum Levels of Retinol-Binding Protein 4 and Adiponectin in Women with Polycystic Ovary Syndrome: Associations with Visceral Fat But No Evidence for Fat Mass-Independent Effects on Pathogenesis in This Condition

Barber, Thomas M.; Hazell, Matthew; Christodoulides, Constantinos; Golding, Stephen J.; Alvey, Christopher; Burling, Keith; Vidal-Puig, António; Groome, Nigel P.; Wass, John; Franks, Stephen; McCarthy, Mark I.

doi:10.1210/jc.2007-2759

Cited by 41 publications

(38 citation statements)

References 40 publications

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“…Albumin was measured by Laurell rocket immunoelectrophoresis, using polyclonal antiserum from International Immunology (Murrieta, CA). Adiponectin (total and high molecular mass) was assayed by an "in house" ELISA, using monoclonal antibodies as described previously (2). Low-molecular mass adiponectin concentrations were calculated by subtraction of high molecular mass from total concentrations.…”

Section: Methodsmentioning

confidence: 99%

Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport

Miller

Michel

Nanjee

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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Peptides secreted by adipose tissue (adipokines) may enter blood via capillaries or lymph. The relative importance of these pathways for a given adipokine might influence its biological effects. Because this has not been studied in any species, we measured the concentrations of seven adipokines and eight nonsecreted proteins in afferent peripheral lymph and venous plasma from 12 healthy men. Data for nonsecreted proteins were used to derive indices of microvascular permeability, which in conjunction with the molecular radii of the adipokines were used to estimate the amounts leaving the tissue via capillaries. Transport rates via lymph were estimated from the lymph adipokine concentrations and lymph flow rates and total transport (secretion) as the sum of this and capillary transport. Concentrations of nonsecreted proteins were always lower in lymph than in plasma. With the exception of adiponectin, adipokine concentrations were always higher in lymph (P < 0.01). Leptin and MCP-1 were secreted at the highest rates (means: 43 μg/h or 2.7 nmol/h and 32 μg/h or 2.4 nmol/h, respectively). IL-6 and MCP-1 secretion rates varied greatly between subjects. The proportion of an adipokine transported via lymph was directly related to its molecular radius (r(s) = +0.94, P = 0.025, n = 6), increasing from 14 to 100% as the radius increased from 1.18 (IL-8) to 3.24 nm (TNFα). We conclude that the lymph/capillary partitioning of adipokines is a function of molecular size, which may affect both their regional and systemic effects in vivo. This finding may have implications for the physiology of peptides secreted by other tissues.

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Section: Methodsmentioning

confidence: 99%

Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport

Miller

Michel

Nanjee

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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“…Although this topic has been investigated by many research groups, there is still no clear evidence of a direct relationship between hypoadiponectinemia and PCOS. A number of studies showed an independent decrease in adiponectin levels in PCOS patients [108,[112][113][114][115][116][117][118], but others failed to demonstrate a direct link between hypoadiponectinemia and PCOS [119][120][121][122][123][124][125][126][127][128][129]. Whether hypoadiponectinemia is or is not directly implicated in the development of PCOS, it surely participates in the insulin-resistant state observed in those patients, and there has been speculation that hypoadiponectinemia could be used to identify women with PCOS who are at higher risk for the future development of type 2 diabetes [130] and coronary artery diseases (CAD) [117].…”

Section: Polycystic Ovary Syndromementioning

confidence: 99%

Adiponectin action from head to toe

Brochu-Gaudreau

Rehfeldt

Blouin

et al. 2009

Endocr

280

247

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Adiponectin, the most abundant protein secreted by white adipose tissue, is known for its involvement in obesity-related disorders such as insulin resistance, type 2 diabetes mellitus and atherosclerosis. Moreover, modulation of the circulating adiponectin concentration is observed in pathologies that are more or less obesity-related, such as cancer and rheumatoid arthritis. The wide distribution of adiponectin receptors in various organs and tissues suggests that adiponectin has pleiotropic effects on numerous physiological processes. Besides its well-known insulin-sensitizing, anti-inflammatory and antiatherosclerotic properties, accumulating evidence suggests that adiponectin may also have anticancer properties and be cardioprotective. A beneficial effect of adiponectin on female reproductive function was also suggested. Since adiponectin has numerous beneficial biological functions, its use as a therapeutic agent has been suggested. However, the use of adiponectin or its receptors as therapeutic targets is complicated by the presence of different adiponectin oligomeric isoforms and production sites, by multiple receptors with differing affinities for adiponectin isoforms, and by cell-type-specific effects in different tissues. In this review, we discuss the known and potential roles of adiponectin in various tissues and pathologies. The therapeutic promise of administration of adiponectin and the use of its circulating levels as a diagnostic biomarker are further discussed based on the latest experimental studies.

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“…One possible postulated mechanism is up-regulation of mRNA RBP4 by 17β-estradiol, a hormone derived from testosterone that is mainly responsible for PCOSassociated clinical hyperandrogenism [7]. However, in contrast to these results, a few previous studies [8,26,27] have stated that there are no differences in RBP4 levels between PCOS cases and controls and have suggested a primary role of RBP4 in the development of PCOS. It is possible that this process involves other molecular mechanisms that remain to be elucidated.…”

Section: Discussionmentioning

confidence: 92%

“…In overweight women with PCOS compared with controls, enhanced expression of RBP4 in adipose tissue and elevated serum RBP4 have been described [7]. In a study involving 50 women with PCOS and 28 control women, the result showed indistinguishable levels of RBP4 between the two groups [8]. In a subsequent study on 27 lean women with PCOS and 19 age-and body mass index-matched controls, RBP4 levels were also shown to be similar between the two groups [9].…”

Section: Description Of the Studiesmentioning

confidence: 98%

Association between retinol-binding protein 4 and polycystic ovary syndrome: A meta-analysis

et al. 2014

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POLYCYSTIC OVARY SYNDROME (PCOS) is the most common endocrinopathy in women of reproductive age, with a prevalence of up to 10%. It is a heterogeneous syndrome with the characteristics of hirsutism, acne, anovulation, hyperandrogenemia, polycystic ovaries, and infertility [1]. It is associated with an adverse metabolic profile including insulin resistance. There is a clear association between obesity, the development of PCOS, and the severity of its phenotypic, biochemical and metabolic features [2]. About 50% of PCOS patients are obese [3]. It is currently assumed that adipose tissue is not only the main energy reservoir but also a pivotal endocrine organ secreting a variety of bioactive cytokines named adipokines, such as leptin, resis- Abstract. Studies have examined the association between retinol-binding protein 4 (RBP4) and polycystic ovary syndrome (PCOS). However, the results have been inconsistent. To investigate the association between RBP4 and PCOS, we performed a meta-analysis. The Cochrane Library, MEDLINE, the ISI Web of Science, and EMBASE were searched to identify all of the studies that examined the relationship between circulating RBP4 levels and PCOS. Standard mean difference (SMD) values and 95% confidence interval (CI) were estimated and pooled using meta-analysis methodology. A total of seven studies were involved in the meta-analysis, which included a total of 636 subjects (260 controls and 376 patients with PCOS). The RBP4 level was higher in PCOS patients than in non-PCOS patients (random effects MD (95% CI)=0.69, [0.20, 1.18], P=0.006). However, the RBP4 level was not higher in nonobese PCOS patients than in nonobese controls (random effects MD (95% CI)=0.38, [-0.21, 0.98], P=0.20). The effect size revealed that the RBP4 level was higher in overweight or obese PCOS patients than weight-matched controls (fixed effects MD (95% CI) =7.95, [5.96, 9.93], P<0.05). In the subgroup analysis by region, the RBP4 level was higher in PCOS patients in Asia than controls (random effects MD (95% CI)=0.85, [0.54, 1.15], P<0.05), but not in European PCOS patients compared with controls (random effects MD (95% CI)=0.34, [-1.12, 1.80], P=0.65). This subgroup analysis also showed that nonobese PCOS patients have higher RBP4 levels than controls in Asia. Our meta-analysis results indicated that RBP4 might be a useful tool for identifying PCOS women.

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Serum Levels of Retinol-Binding Protein 4 and Adiponectin in Women with Polycystic Ovary Syndrome: Associations with Visceral Fat But No Evidence for Fat Mass-Independent Effects on Pathogenesis in This Condition

Abstract: Although associated with visceral fat, serum RBP4 and adiponectin levels do not play important, fat-mass-independent primary roles in the development of PCOS.

Cited by 41 publications

References 40 publications

Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport

Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport

Adiponectin action from head to toe

Association between retinol-binding protein 4 and polycystic ovary syndrome: A meta-analysis

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