Dr. Bing Li received a five-year NIH U01 award entitled “Determine the Molecular and Metabolic Mechanisms by which A-FABP Links Dysregulated Lipid Metabolism-induced Obesity/Breast Cancer Risk”. This award in combination with four other selected projects and a Coordinating Center will constitute the National Cancer Institute (NCI) Metabolic Dysregulation and Cancer Risk Program, which will focus on metabolic dysregulation as the key process linking obesity with cancer risk.

Epidemiologic studies have confirmed that obesity increases the risk and mortality of breast cancer (BC), but the molecular mechanisms of obesity/BC associations remain largely unknown. Our recent studies demonstrate that the lipid chaperone A-FABP (adipose fatty acid binding protein, also known as FABP4) promotes obesity-associated BC by intracellular regulation of pro-tumor activity in tumor associated macrophages (TAMs) and extracellular enhancement leading to an aggressive phenotype of BC cells. Thus, A-FABP might represent a new factor linking dysregulated lipid metabolism with obesity/BC risk. Moreover, we observed that obesity can be induced by consumption of different types of high-fat diets (HFDs), including saturated fats (e.g. cocoa butter) or unsaturated fats (e.g. olive oil, fish oil). However, cocoa butter HFD-induced obesity was associated with increased A-FABP expression and mammary tumor growth. These observations suggest a novel concept that not all HFD-induced obesity is tumorigenic. Given the undefined links underlying obesity-induced BC risk, we will determine if HFDs rich in saturated fats promote BC risk through A-FABP-mediated immune and metabolic regulation. As such, A-FABP offers a novel therapeutic target and biomarker for obesity-associated BC risk.