Adipose tissue is an active metabolic tissue that secretes multiple metabolically important proteins, known as adipokines. Adiponectin is an important adipokine because of its beneficial effects on glucose and lipid metabolism. Low levels of adiponectin are associated with disease states such as diabetes and cardiovascular disease. Direct administration of adiponectin has been shown to be beneficial in animal models of diabetes, obesity and atherosclerosis. Adiponectin levels in humans can be increased through indirect methods such as weight loss or treatment with thiazolidinediones. This article will review the epidemiology and therapeutic options with adiponectin.

Background: Age at diagnosis is incorporated into all relevant staging systems for differentiated thyroid carcinoma (DTC). There is growing evidence that a specific age cutoff may not be ideal for accurate risk stratification. We sought to evaluate the interplay between age and oncologic variables in patients with DTC using the largest cohort to date. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with DTC as their only malignancy for the period 1973 to 2009. Multivariate analyses using a range of age cutoffs and age subgroupings were utilized in order to search for an optimal age that would provide the most significant risk stratification between young and old patients. The primary outcome was disease-specific survival (DSS) and covariates included: age, race, sex, tumor/nodal/metastasis (TNM) stage, decade of diagnosis, and radioactive iodine therapy. Results: A total of 85,740 patients were identified. Seventy-six percent of patients were American Joint Committee on Cancer (AJCC) stage I, 8% were stage II, 7% were stage III, and 8% were stage IV. Age over 45 years (hazard ratio [HR] 19.2, p < 0.001) and metastatic disease (HR 13

To test the hypothesis that depot differences exist for adiponectin, fresh and cultured human VAT and SAT from obese type 2 diabetic (T2D) and obese nondiabetic (ND) subjects was examined to determine whether differences in adiponectin content and secretion occurred as a function of depot studied, diabetic status, and response to thiazolidinedione treatment. VAT and SAT were obtained by biopsy and AT explants cultured in defined media for 7 days. Protein expression was assessed by Western blot. Adiponectin content of conditioned medium was determined by radioimmunoassay. Diabetic status had no effect on adiponectin secretion over days 0 -2 of culture. In ND SAT, secretion fell over days 2-4 but was sustained at greater levels vs. T2D SAT. In both ND and T2D VAT, adiponectin secretion was low, similar to T2D SAT. Over the 7-day culture period, cellular adiponectin increased in ND SAT and VAT; it remained unchanged in T2D SAT and VAT. Pioglitazone increased adiponectin secretion and content in all SAT. Pioglitazone failed to increase adiponectin secretion from either ND or T2D VAT and increased cellular content only in ND VAT. AT depot differences exist in the secretion of adiponectin and responsiveness to thiazolidinedione treatment. These data suggest that SAT, not VAT, appears to be the major contributor to increased circulating adipopnectin levels in response to pioglitazone treatment. adipose tissue physiology; type 2 diabetes mellitus; body fat distribution; thiazolidinediones; leptin ADIPOSE TISSUE (AT) is recognized to play an important role in the regulation of lipid/carbohydrate metabolism, energy homeostasis, and insulin sensitivity (55) via release of metabolically active products that regulate insulin sensitivity and fat metabolism (27). Many AT products exert opposing actions on insulin sensitivity, inflammation, and fatty acid metabolism. For example, AT products IL-6, TNF-␣, and resistin may impair insulin sensitivity, increase circulating free fatty acids, and exert proinflammatory effects, whereas others such as adiponectin exert insulin-sensitizing effects, reduce free fatty acids, and dampen inflammation (28). The metabolic impact of a given AT depot is therefore related to the relative profile or balance of mediator release.AT is distributed to a variety of locations, and in humans contributions of SAT and VAT can be distinguished (reviewed in Ref. 59). Individuals with increased visceral (V)AT are at higher risk of developing the metabolic syndrome, type 2 diabetes (T2D), and cardiovascular disease (32, 59) than those with similar amounts of AT as subcutaneous (S)AT (34). Underlying these findings are depot differences in gene and protein expression (36, 37). These findings lend support to the idea that different AT depots are functionally distinct metabolic units.Circulating levels of adiponectin are low in obese and insulin-resistant subjects (62) and are predictive for development of T2D (30). In contrast, adiponectin is high in lean and insulin-sensitive subjects (50). Interestingly, seru...

Glycogen synthase kinase-3 (GSK-3) is a ubiquitous kinase implicated in both insulin action and adipogenesis. To determine how these multiple roles may relate to insulin resistance, we studied the regulation of GSK-3 protein expression and phosphorylation in skeletal muscle and isolated adipocytes from nonobese healthy control (HC), obese control (OC), and obese type 2 diabetic (OT2D) subjects. At baseline there were no differences in the GSK-3 protein expression in adipocytes. OC subjects underwent a 6-mo caloric restriction resulting in a 7% decrease in body mass index (BMI) and a 21% improvement in insulin-stimulated whole body glucose disposal rate (GDR). GSK-3alpha and GSK-3beta expression decreased in adipocytes (P < 0.05), whereas GSK-3alpha protein expression increased in skeletal muscle (P < 0.05). OT2D subjects were treated with troglitazone or metformin for 3-4 mo. After troglitazone treatment GDR improved (P < 0.05) despite an increase in BMI (P < 0.05), whereas metformin had no significant effect on GDR. There was no significant change in GSK-3 expression in adipocytes following troglitazone, whereas both GSK-3alpha and -beta were decreased in skeletal muscle (P < 0.05). Metformin treatment had no significant impact on GSK-3 protein expression in either adipocytes or skeletal muscle. Neither treatment influenced GSK-3 serine phosphorylation in skeletal muscle or adipocytes. These results suggest that there is tissue specificity for the regulation of GSK-3 in humans. In skeletal muscle GSK-3 plays a role in control of metabolism and insulin action, whereas the function in adipose tissue is less clear.