For better or worse: FFAR1 and FFAR4 signaling in cancer and diabetes

Abstract

Increased energy intake can lead to obesity, which increases the risk for the development of diabetes and cancer. Free fatty acids regulate numerous cellular processes, like insulin secretion, inflammation, proliferation, and cell migration. Dysregulation of these cellular functions by increased lipid intake plays a significant role in the development of diseases like diabetes and cancer. Free fatty acid receptors 1 and 4 (FFAR1 and FFAR4) are two free fatty acid receptors under increasing investigation for their roles in diabetes and more recently also cancer. Both receptors bind medium-to long-chain, saturated and omega-3 unsaturated fatty acids. Increasing evidence shows that enhanced FFAR1 and FFAR4 signaling reduces diabetes symptoms but enhances tumor growth and migration of various cancer types like melanoma and prostate cancer. This review gives an overview of the role of FFAR1 and FFAR4 in diabetes and cancer and discusses their potential to function as targets for treatment.