TY - JOUR
T1 - Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer
AU - Zahid, Heba
AU - Simpson, Evan R.
AU - Brown, Kristy A.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat. The regulation of aromatase in the breast adipose stromal cell in response to inflammatory mediators is under the control of complex signaling pathways, including metabolic pathways involving LKB1/AMPK, p53, HIF1α and PKM2. Interventions aimed at modifying weight, including diet and exercise, are associated with changes in adipose tissue inflammation and estrogen production that are likely to impact breast cancer risk. This review will present an overview of these topics.
AB - Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis. This occurs not only in the visceral and subcutaneous fat, but also in the breast fat. The regulation of aromatase in the breast adipose stromal cell in response to inflammatory mediators is under the control of complex signaling pathways, including metabolic pathways involving LKB1/AMPK, p53, HIF1α and PKM2. Interventions aimed at modifying weight, including diet and exercise, are associated with changes in adipose tissue inflammation and estrogen production that are likely to impact breast cancer risk. This review will present an overview of these topics.
UR - http://www.scopus.com/inward/record.url?scp=84996946601&partnerID=8YFLogxK
U2 - 10.1016/j.coph.2016.11.003
DO - 10.1016/j.coph.2016.11.003
M3 - Review Article
AN - SCOPUS:84996946601
SN - 1471-4892
VL - 31
SP - 90
EP - 96
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
ER -