Ketogenic Diet and microRNAs Linked to Antioxidant Biochemical Homeostasis

The World Health Organization stands that obesity has nearly tripled since 1975. In 2016, more than 1.9 billion adults were overweight. Of these, over 650 million were obese here a report sentence “Most of the world’s population live in countries where overweight and obesity kills more people than underweight. Obesity is preventable”1. A way is represented by the Ketogenic Diet (KD). KD is safe and the beneficial effects of KD in reducing the bodyweight of obese subjects was already proven2,3. Obesity and epigenetic is a consolidated union4,5 and bariatric surgery induces epigenetic change6. We recently reported the influence of the KD on circulating epigenetic markers called microRNAs (miRs)2. Here we show that 11 miRs controlling the metabolic network previously identified in subjects on KD were almost normalized and closer to lean subjects. Heatmap coming from direct miRs hybridization show that 12 obese subjects on KD normalized the expression levels of hsa-let-7b-5 (8/12) hsa-miR-143-3p (9/12), hsa-miR-148b-3p (10/12), hsa-miR-590-5p (10/12), hsa-miR-520h (8/12) and hsa-miR-644a (9/12) in more than 65% of subjects. 100% was achieved for hsa-miR-548d-3p (12/12). While the 50% was reached for hsa-miR-26a-5p (6/12), and hsa-miR-502-5p (7/12). Any change was seen for hsa-miR-504-5p. The newly hsa-miR-let7e-5p (5/12) and hsa-miR-877 (5/12) identified shown less than 50% of presence with the exception of hsa-miR-30a-5p (8/12). In silico interaction of this latter was found to target 3ʹUTR regions of catalase (CAT) gene that was monitored through western blot analysis. CAT was found decreased after KD regime. String analysis shows that CAT directly or indirectly took physical interaction with Glutathione Peroxidase 7 (GPX7), Tet Methylcytosine Dioxygenase 3 (TET3) and Superoxide Dismutase 2 (SOD2) also targeted by hsa-miR-let7e-5p has-miR520h and hsa-miR-548d-3p respectively. In conclusion, KD is able to regulate miRs linked to antioxidant biochemical pathways. Reference 1. Lopomo A, Burgio E, Migliore, L. Epigenetics of Obesity. Progress in molecular biology and translational science. 2016;140:151-84. Epub 2016/06/12. 2. Cannataro R, Perri M, Gallelli L, Caroleo MC, De Sarro, G., Cione, E. Ketogenic Diet Acts on Body Remodeling and MicroRNAs Expression Profile. Microrna. 2019;8(2):116-26. Epub 2018/11/27. 3. Dashti HM, Mathew TC, Hussein T, Asfar SK, Behbahani A, Khoursheed MA, Al-Sayer HM, Bo-Abbas YY, Al-Zaid NS. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol. 2004 Fall;9(3):200-5. PubMed PMID: 19641727; PubMed Central PMCID: PMC2716748.Tan BL, Norhaizan ME, Liew WP. Nutrients and Oxidative Stress: 4.Izquierdo AG, Crujeiras AB. Obesity-Related Epigenetic Changes After Bariatric Surgery. Frontiers in endocrinology. 2019;10:232. Epub 2019/05/02. 5. Sato F, Tsuchiya S, Meltzer SJ, Shimizu, K. MicroRNAs and epigenetics. The FEBS journal. 2011;278(10):1598-609. Epub 2011/03/15. 6. Hildebrand D, Eberle ME, Wolfle SM, Egler F, Sahin D, Sahr A, et al. Hsa-miR-99b/let-7e/miR-125a Cluster Regulates Pathogen Recognition Receptor-Stimulated Suppressive Antigen-Presenting Cells. Frontiers in immunology. 2018;9:1224. Epub 2018/07/04.