Cancer depends on fatty acids for ATP production: A possible link between cancer and obesity. (November 2022)

• Record Type: Journal Article
• Authors: Lee, Ho; Woo, Sang Myung; Jang, Hyonchol; Kang, Mingyu; Kim, Soo-Youl
• Is Part Of: Seminars in cancer biology. Volume 86(2023)Part 2
• Page Start: 347
• Page End: 357
• Publication Date: 2022-11
• Subjects: Cancer energy metabolism -- Fatty acid oxidation -- ATP production -- Obesity; Cancer -- Periodicals; Neoplasms -- Periodicals; Review Literature; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.semcancer.2022.07.005
• Languages: English
• ISSNs: 1044-579X

Abstract

Abstract: Several metabolic pathways for the supply of adenosine triphosphate (ATP) have been proposed; however, the major source of reducing power for ADP in cancer remains unclear. Although glycolysis is the source of ATP in tumors according to the Warburg effect, ATP levels do not differ between cancer cells grown in the presence and absence of glucose. Several theories have been proposed to explain the supply of ATP in cancer, including metabolic reprograming in the tumor microenvironment. However, these theories are based on the production of ATP by the TCA-OxPhos pathway, which is inconsistent with the Warburg effect. We found that blocking fatty acid oxidation (FAO) in the presence of glucose significantly decreased ATP production in various cancer cells. This suggests that cancer cells depend on fatty acids to produce ATP through FAO instead of glycolysis. We observed that cancer cell growth mainly relies on metabolic nutrients and oxygen systemically supplied through the bloodstream instead of metabolic reprogramming. In a spontaneous mouse tumor model ( Kras G12D ; Pdx1-cre ), tumor growth was 2-fold higher in mice fed a high-fat diet (low-carbo diet) that caused obesity, whereas a calorie-balanced, low-fat diet (high-carbo diet) inhibited tumor growth by 3-fold compared with that in mice fed a control/normal diet. This 5-fold difference in tumor growth between mice fed low-fat and high-fat diets suggests that fat-induced obesity promotes cancer growth, and tumor growth depends on fatty acids as the primary source of energy. Graphical Abstract: ga1 Highlights: All living cells produce ATP in mitochondria using the TCA cycle or fatty acid oxidation (FAO). However, cancer cells do not use carbohydrates for the TCA cycle because of the Warburg effect. Therefore, cancer cells must rely on OxPhos with the ETC using fatty acids supplied from blood vessels to produce ATP.