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Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

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1. In mouse models of polycystic ovarian syndrome (PCOS), elevated adiponectin levels ameliorated metabolic dysfunction.

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2. However, adiponectin was unable to completely restore reproductive function.

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Evidence Rating Level: 3 (Fair)

Study Rundown:

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PCOS is the most common disorder affecting metabolism and reproduction in females. Patients with this syndrome have an elevated risk of developing type 2 diabetes due to increased insulin insensitivity, as well as obesity. The etiology of PCOS is currently unknown, but patients have been found to have decreased levels of adiponectin, a hormone known to improve insulin sensitivity. Therefore, the researchers in this study used PCOS genetic mouse models to evaluate the potential of elevated adiponectin for reproductive and metabolic protection.

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Experiments on the effects of increased adiponectin on reproductive function showed mixed results. Mice with elevated levels of adiponectin did not develop the increased number of cystic ovarian follicles characteristic of PCOS mice. However, these mice showed no improvement in terms of altered reproductive cycles. Adiponectin was successful in improving the metabolic defects associated with PCOS. Mice with elevated adiponectin levels did not develop increased weight gain and showed smaller adipocytes compared to controls. These mice were also more sensitive to insulin and did not have the metabolic gene expression defects associated with PCOS.

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This study found that adiponectin was protective against the metabolic abnormalities that develop in PCOS, and suggests the use of adiponectin as a therapeutic for PCOS patients. Further work should focus on a clinically viable mechanism for delivering adiponectin, as well as assess optimal dosing and safety.

In-Depth [animal study]:

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Adiponectin knockout (APNko) and overexpressing transgenic (APNtg) mice were used to assess the lack of adiponectin or elevated adiponectin levels, respectively. To induce PCOS, dihydrotestosterone (DHT) was administered to these and control wild-type (WT) mice. APNtg mice did not demonstrate a significant increase in the number cystic follicles, while WT and APNko mice did (p<0.01). Despite this finding, APNtg mice showed the abnormal estrus cycling characteristic of PCOS.

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Metabolically, DHT exposure in APNtg mice did not affect the expression of genes involved in the production of sex hormones, including Cyp19a1 and Hsd3b. In contrast, DHT-exposed WT and APNko mice experienced significant changes in the expression of these genes (p<0.05). APNtg mice did not develop increased weight gain compared to the other mouse models, and showed a trend of smaller adipocytes.

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APNtg mice showed insulin sensitivity and greater tolerance to glucose (p<0.05). When the pancreas was analyzed, APNtg did not show a significant increase in insulin expression, and had elevated levels of beta cell viability markers including Pdx1. These mice also displayed elevated levels of the insulin receptor, Igf1. Additionally, the decreased gene expression in gonadal adipose tissue observed in WT and APNko mice was not seen in the APNtg mice.

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