ω-3 and ω-6 Polyunsaturated Fatty Acids, Obesity and Cancer

Abstract

Recently, nutraceutical bioactive compounds in foods have been discovered for their potential health benefits regarding the prevention of chronic disorders, such as cancer, and inflammatory, cardiovascular, and metabolic diseases. Dietary omega-3 polyunsaturated fatty acids (ω-3PUFAs), including alpha-linolenic acid, docosapentaenoic acid, and eicosapentaenoic acid, are mostly attractive. They are available for the customers worldwide from commonly used foods and/or as components of commercial food supplements. The anti-inflammatory and hypotriglyceridemic effects of these fatty acids are well known, whereas pro-inflammatory properties have been recognized in their dietary counterparts, the ω-6PUFAs. Both ω-3 and ω-6PUFAs contribute to the production of lipid mediators such as endocannabinoids that are notably involved in control of food intake, energy sensing, and food-related disorders. In this review, we present ω-3 and ω-6PUFAs and their derivatives, endocannabinoids; discuss the anti-obesity effects of ω-3PUFAs; their roles in inflammation and colorectal cancer development; and how their action can be co-preventative and co-therapeutic.

Keywords: CRC; endocannabinoids; fatty acids; obesity; ω-3PUFAs; ω-6PUFAs.

Figure 1

Essential fatty acids and dietary source (AA: arachidonic acid; ALA: α-linolenic acid; DHA: docosahexaenoic acid; EPA: eicosapentaenoic acid; LA: linoleic acid; PUFA: polyunsaturated fatty acid).

Figure 2

A schematic representation of the metabolic/hydrolyzing pathways linking ω-3 and ω-6, endocannabinoids, and inflammatory mediators. The syntheses of DHEA and EPEA, and AEA from ω-3 and ω-6 PUFAs respectively, requires the activity of N-acetyltransferase (NAT) followed by N-acyl phosphatidylethanolamine-specific phospholipase D (NAPEPLD). The synthesis of 2-AG from ω-6 PUFAs requires the subsequent activity of phospholipase Cβ (PLCâ) and diacylglycerol lipase (DAGL). The hydrolysis of the endocannabinoids requires the activity of the fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). The activity of lipoxygenases (LOX), cyclooxygenase (COX), and cytochrome P450 enzymes (CyP450) drives the production of inflammation mediators. AA: arachidonic acid; AEA: anandamide; 2-AG: 2-arachinonoylglycerol; DHA: docosahexaenoic acid; DHEA: N-docosahexaenoyl ethanolamine; EPA: eicosapentaenoic acid; EPEA: N-eicosapentanoyl ethanolamine; Mar1: maresin 1; NPD1: neuroprotectin D1; PUFA: polyunsaturated fatty acid; RvD1: resolvin D1.

Figure 3

Some signaling mechanisms mediating effects of ω-3PUFAs (AMPK: AMP-activated protein kinase; FFAR: free fatty acid receptor; IL-: Interleukin-; MCP-1: Monocyte chemo attractant protein 1; NF-kB: nuclear factor-κB; PGE2: Prostaglandin E2; PPAR: Peroxisome proliferator-activated receptor; PUFA: polyunsaturated fatty acid; TNF-α: Tumor necrosis factor-alpha).