Obesity and cancer progression: is there a role of fatty acid metabolism?

Abstract

Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine and de novo lipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

Figure 1

Intracellular fatty acid metabolism. A simplified cartoon of fatty acid metabolism pathways. Fatty acids are transported in the circulation as triacylglycerol (TAG) in lipoproteins and hydrolyzed by lipoprotein lipase (LPL) or they are bound to albumin and are transported across the plasma membrane. A CoA is ligated to fatty acid (FA), and the fatty acyl-CoA (FA-CoA) can enter the glycerolipid synthesis pathway for storage or the mitochondria for oxidation. ACS, acyl-CoA synthase; AGPAT, acyl-CoA: acylglycerol-3-phosphate acyltransferase; ATGL, adipose triglyceride lipase; DAG, diacylglycerol; DGAT, diacylglycerol acyltransferase; GPAT, glycerol-3-phosphate acyltransferase; HSL, hormone-sensitive lipase; LPA, lysophosphatidic acid; MAG, monoacylglycerol; MAGL, monoacylglycerol lipase; PA, phosphatidic acid.