Deletion of the androgen receptor in adipose tissue in male mice elevates retinol binding protein 4 and reveals independent effects on visceral fat mass and on glucose homeostasis.

Testosterone deficiency is epidemic in obese ageing males with type 2 diabetes, but the direction of causality remains unclear. Testosterone-deficient males and global androgen receptor (AR) knockout mice are insulin resistant with increased fat, but it is unclear whether AR signaling in adipose tissue mediates body fat redistribution and alters glucose homoeostasis. To investigate this, mice with selective knockdown of AR in adipocytes (fARKO) were generated.

Regulation of LKB1 expression by sex hormones in adipocytes.

Objective: In the adipose tissue, activation of AMP-activated protein kinase (AMPK) by phosphorylation favours local fatty acid oxidation and inhibition of lipogenesis. We have previously shown that the potent androgen dihydrotestosterone (DHT) can inhibit phosphorylation of AMPK in adipose tissue and 3T3-L1 adipocytes in a dose-dependent manner. This negative effect of DHT was reversed by oestrogen treatment.

LKB1 expression is inhibited by estradiol-17β in MCF-7 cells.

The liver kinase B1 (LKB1) is encoded by the STK11 gene and acts as a tumour suppressor and a regulator of energy homeostasis. LKB1 expression is reduced in primary breast tumours compared to normal breast epithelium. Although its expression in primary tumours does not appear to correlate with estrogen receptor (ER) status, it is differentially expressed in breast cancer cell lines where ER-negative cells have lower LKB1 expression than ER-positive cells.

Constituents from Cistus salvifolius (Cistaceae) activate peroxisome proliferator-activated receptor-γ but not -δ and stimulate glucose uptake by adipocytes.

A number of medicinal/culinary herbs have been reported to improve glucose metabolism and to yield hypoglycemic effects in patients with diabetes. Since stimulation of insulin sensitivity appears to be a potential mechanism, peroxisome proliferator-activated receptor (PPAR) γ is a likely target molecule for small lipophilic compounds derived from endogenous metabolism and nutrition. Functionally, PPAR γ integrates the control of energy, lipid, and glucose homeostasis.

Metformin inhibits aromatase expression in human breast adipose stromal cells via stimulation of AMP-activated protein kinase.

AMP-activated protein kinase (AMPK) is recognized as a master regulator of energy homeostasis. In concert with the AMPK-kinase LKB1, it has been shown to provide a molecular link between obesity and postmenopausal breast cancer via its actions to inhibit aromatase expression, hence estrogen production, within the breast. The anti-diabetic drug metformin is known to increase the activity of AMPK and was therefore hypothesized to inhibit aromatase expression in primary human breast adipose stromal cells.

Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women.

Epidemiologic evidence supports a correlation between obesity and breast cancer in women. AMP-activated protein kinase plays an important role in energy homeostasis and inhibits the actions of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 (CRTC2). In postmenopausal women, the cyclic AMP-responsive element binding protein-dependent regulation of aromatase is a determinant of breast tumor formation through local production of estrogens.