targeting amp-activated protein kinase in adipocytes to modulate obesity-related adipokine production associated with insulin resistance and breast cancer cell proliferation针对在脂肪细胞活化蛋白激酶调节与肥胖相关的adipokine生产与胰岛素抵抗和乳腺癌细胞增殖有关.pdf

Grisouard et al. Diabetology Metabolic Syndrome 2011, 3:16 DIABETOLOGY /content/3/1/16 METABOLIC SYNDROME SHORT REPORT Open Access Targeting AMP-activated protein kinase in adipocytes to modulate obesity-related adipokine production associated with insulin resistance and breast cancer cell proliferation 1* 1 2 1,3 4 1,3 Jean Grisouard , Kaethi Dembinski , Doris Mayer , Ulrich Keller , Beat Müller and Mirjam Christ-Crain Abstract Background: Adipokines, e.g. TNFa, IL-6 and leptin increase insulin resistance, and consequent hyperinsulinaemia influences breast cancer progression. Beside its mitogenic effects, insulin may influence adipokine production from adipocyte stromal cells and paracrine enhancement of breast cancer cell growth. In contrast, adiponectin, another adipokine is protective against breast cancer cell proliferation and insulin resistance. AMP-activated protein kinase (AMPK) activity has been found decreased in visceral adipose tissue of insulin- resistant patients. Lipopolysaccharides (LPS) link systemic inflammation to high fat diet-induced insulin resistance. Modulation of LPS-induced adipokine production by metformin and AMPK activation might represent an alternative way to treat both, insulin resistance and breast cancer. Methods: Human preadipocytes obtained from surgical biopsies were expanded and differentiated in vitro into adipocytes, and incubated with siRNA targeting AMPKalpha1 (72 h), LPS (24 h, 100 μg/ml) and/or metformin (24 h, 1 mM) followed by mRNA e