The role of glucocorticoids in the induction of zinc-α2-glycoprotein expression in adipose tissue in cancer cachexia

Loss of adipose tissue in cancer cachexia in mice bearing the MAC16 tumour arises from an increased lipid mobilisation through increased expression of zinc-α2-glycoprotein (ZAG) in white (WAT) and brown (BAT) adipose tissue. Glucocorticoids have been suggested to increase ZAG expression, and this study examines their role in cachexia and the mechanisms involved. In mice bearing the MAC16 tumour, serum cortisol concentrations increased in parallel with weight loss, and the glucocorticoid receptor antagonist RU38486 (25 mg kg−1) attenuated both the loss of body weight and ZAG expression in WAT. Dexamethasone (66 μg kg−1) administration to normal mice produced a six-fold increase in ZAG expression in both WAT and BAT, which was also attenuated by RU38486. In vitro studies using 3T3-L1 adipocytes showed dexamethasone (1.68 μM) to stimulate lipolysis and increase ZAG expression, and both were attenuated by RU38486 (10 μM), anti-ZAG antibody (1 μgml−1), and the β3-adrenoreceptor (β3-AR) antagonist SR59230A (10 μM). Zinc-α2-glycoprotein also increased its own expression and this was attenuated by SR59230A, suggesting that it was mediated through the β3-AR. This suggests that glucocorticoids stimulate lipolysis through an increase in ZAG expression, and that they are responsible for the increase in ZAG expression seen in adipose tissue of cachectic mice

Adipocyte-specific glucocorticoid inactivation protects against diet-induced obesity

Local glucocorticoid (GC) action depends on intracellular GC metabolism by 11β-hydroxysteroid dehydrogenases (11βHSDs). 11βHSD1 activates GCs, while 11βHSD2 inactivates GCs. Adipocyte-specific amplification of GCs through transgenic overexpression of 11βHSD1 produces visceral obesity and the metabolic syndrome in mice. To determine whether adipocyte-specific inactivation of GCs protects against this phenotype, we created a transgenic model in which human 11βHSD2 is expressed under the control of the murine adipocyte fatty acid binding protein (aP2) promoter (aP2-h11βHSD2). Transgenic mice have increased 11βHSD2 expression and activity exclusively in adipose tissue, with the highest levels in subcutaneous adipose tissue, while systemic indexes of GC exposure are unchanged. Transgenic mice resist weight gain on high-fat diet due to reduced fat mass accumulation. This improved energy balance is associated with decreased food intake, increased energy expenditure, and improved glucose tolerance and insulin sensitivity. Adipose tissue gene expression in transgenic mice is characterized by decreased expression of leptin and resistin and increased expression of adiponectin, peroxisome proliferator–activated receptor γ, and uncoupling protein 2. These data suggest that reduction of active GCs exclusively in adipose tissue is an important determinant of a favorable metabolic phenotype with respect to energy homeostasis and the metabolic syndrome

The changing ties that bind. Issues surrounding sexuality and health for Greek parents and their Australian-born sons and daughters.

This article examines the changing nature of family values and expectations in relation to sexuality, gender roles, and health among Greek parents and their young adult sons and daughters living in Melbourne, Australia. Findings are reported from a qualitative study involving in-depth interviews with 37 young adult Greek Australian men and women and 7 Greek parents as well as four focus group discussions with 25 parents. Key themes are compared in relation to the tensions relating to changing gender roles and expectations within the family and Greek community. Although these tensions can act as barriers to effective prevention strategies for young second-generation Greek adults, parents acknowledge the need for change to protect their children from HIV/AIDS and STDs. The results support the need for prevention strategies for STDs and HIV/AIDS that build on the importance of close family connections and deal with the tensions surrounding the changing ties that bind