Precision Nutrition for Targeting Lipid Metabolism in Colorectal Cancer

Abstract

Cancer is a multistage and multifactorial condition with genetic and environmental factors modulating tumorogenesis and disease progression. Nevertheless, cancer is preventable, as one third of cancer deaths could be avoided by modifying key risk factors. Nutrients can directly affect fundamental cellular processes and are considered among the most important risk factors in colorectal cancer (CRC). Red and processed meat, poultry consumption, fiber, and folate are the best-known diet components that interact with colorectal cancer susceptibility. In addition, the direct association of an unhealthy diet with obesity and dysbiosis opens new routes in the understanding of how daily diet nutrients could influence cancer prognosis. In the “omics” era, traditional nutrition has been naturally evolved to precision nutrition where technical developments have contributed to a more accurate discipline. In this sense, genomic and transcriptomic studies have been extensively used in precision nutrition approaches. However, the relation between CRC carcinogenesis and nutrition factors is more complex than originally expected. Together with classical diet-nutrition-related genes, nowadays, lipid-metabolism-related genes have acquired relevant interest in precision nutrition studies. Lipids regulate very diverse cellular processes from ATP synthesis and the activation of essential cell-signaling pathways to membrane organization and plasticity. Therefore, a wide range of tumorogenic steps can be influenced by lipid metabolism, both in primary tumours and distal metastasis. The extent to which genetic variants, together with the intake of specific dietary components, affect the risk of CRC is currently under investigation, and new therapeutic or preventive applications must be explored in CRC models. In this review, we will go in depth into the study of co-occurring events, which orchestrate CRC tumorogenesis and are essential for the evolution of precision nutrition paradigms. Likewise, we will discuss the application of precision nutrition approaches to target lipid metabolism in CRC.

Decreased Triacylglycerol Content and Elevated Contents of Cell Membrane Lipids in Colorectal Cancer Tissue: A Lipidomic Study

“…Colorectal cancer (CRC) is one of the most common malignancies worldwide, and its incidence is still increasing [1][2][3][4]. Prevention, treatment and prognosis in CRC cannot be improved any further without a better insight into the pathophysiology of this malignancy [1].…”

“…Based on the comparison of lipid metabolism in various physiological and pathological conditions, identification of critical structures, their functions and interactions with other lipids, proteins, and different metabolites, lipidomics may explain the role of these compounds in metabolic control [1]. Given the important role of lipids at various levels of cell physiology, changes in their metabolism may interfere with a variety of processes, e.g., the control of the plasticity and organization of plasma membranes, or the provision of substrates for ATP synthesis and cell signaling [3]. Some authors have claimed a positive effect of supplementation with various lipids [2,6] or their main structural elements, fatty acids (FAs), in cancer patients [7].…”

“…Some authors have claimed a positive effect of supplementation with various lipids [2,6] or their main structural elements, fatty acids (FAs), in cancer patients [7]. However, the effects of FAs were also shown to depend on the structural group they belong, as well as on their source (de novo synthesis, diet) [3].…”

The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells

“…9 Additionally, clinical studies have revealed a close link between oxidative stress biomarkers and the status and development of CRC. [10][11][12] Nuclear factor erythroid 2-related factor 2 (Nrf2) has long been regarded as an important factor in protecting cells from oxidant stress, due to its regulation of various phase II detoxifying enzymes, such as hemeoxygenase-1 (HO-1), NADP(H):quinone oxidoreductase-1 (NQO1), glutathione S-transferase (GST), UDP-glucuronosyltransferase, and glutamate-cysteine ligase. [13][14][15] Ishaq et al 16 reported that Nrf2 plays a defensive role in HT29 cancer cells by inducing apoptosis via activating caspase-3/7 and protects against oxidative stress-induced genotoxicity.…”

Intestinal microorganisms involved in colorectal cancer complicated with dyslipidosis

“…1,2 High-fat diet can increase the level of saturated fatty acids in peripheral blood and lead to disturbances in lipid metabolism such as hyperlipoidaemia and hypercholesteremia. 3 Epidemiological studies have shown that hyperlipoidaemia and hypercholesteremia can increase the risk of cancer, and hyperlipoidaemia can increase the incidence of CRC. 1 Several investigations have shown that the incidence of lipid metabolism abnormalities in patients with CRC is higher than that in healthy individuals.…”