Research Article

Ketogenic Diet Acts on Body Remodeling and MicroRNAs Expression Profile

Author(s): Roberto Cannataro, Mariarita Perri, Luca Gallelli, Maria Cristina Caroleo, Giovambattista De Sarro and Erika Cione*

Volume 8, Issue 2, 2019

Page: [116 - 126] Pages: 11

DOI: 10.2174/2211536608666181126093903


Background: The Ketogenic Diet (KD) promotes metabolic changes and optimizes energy metabolism. It is unknown if microRNAs (miRs) are influenced by KD in obese subjects. The screening of circulating miRs was performed with the FDA approved platform n-counter flex and blood biochemical parameters were dosed by ADVIA 1800.

Objectives: The aim of this study was to evaluate mir profile under 6 weeks of biphasic KD in obese subjects. We enrolled 36 obese subjects (18 females and 18 males) in stage 1 of Edmonton Obesity Staging System (EOSS) parameter.

Result: Any correlation was found between biochemical parameter and three miRs, hsa-let-7b-5p, hsa-miR-143-3p and hsa-miR-504-5p influenced in an equal manner in both sexes. The KD resulted safe and ameliorate both biochemical and anthropometric factors in obese subjects re-collocating them into stage 0 of EOSS parameters.

Conclusion: The miRs herein identified under KD might be a useful tool to monitor low carbohydrate nutritional regimens which reflect indirectly the regulatory biochemical mechanisms and cell signaling that orchestrate metabolic and signaling pathways.

Keywords: Anthropometric parameters, ketogenic diet program, microRNAs, body weight, obesity, metabolism.

Graphical Abstract
Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab 2003; 88(4): 1617-23.
Brownlow ML, Jung SH, Moore RJ, Bechmann N, Jankord R. Nutritional ketosis affects metabolism and behavior in Sprague-Dawley rats in both control and chronic stress environments. Front Mol Neurosci 2017; 10: 129.
Castaldo G, Palmieri V, Galdo G, et al. Aggressive nutritional strategy in morbid obesity in clinical practice: safety, feasibility, and effects on metabolic and haemodynamic risk factors. Obes Res Clin Pract 2016; 10(2): 169-77.
Dashti HM, Mathew TC, Hussein T, et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol 2004; 9(3): 200-5.
Gibson AA, Seimon RV, Lee CM, et al. Do ketogenic diets really suppress appetite? A systematic review and meta-analysis. Obes Rev 2015; 16(1): 64-76.
Sumithran P, Prendergast LA, Delbridge E, et al. Ketosis and appetite-mediating nutrients and hormones after weight loss. Eur J Clin Nutr 2013; 67(7): 759-64.
Bueno NB, de Melo IS, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr 2013; 110(7): 1178-87.
Paoli A. Ketogenic diet for obesity: friend or foe? Int J Environ Res Public Health 2014; 11(2): 2092-107.
Giordano C, Marchio M, Timofeeva E, Biagini G. Neuroactive peptides as putative mediators of antiepileptic ketogenic diets. Front Neurol 2014; 5: 63.
Stafstrom CE, Rho JM. The ketogenic diet as a treatment paradigm for diverse neurological disorders. Front Pharmacol 2012; 3: 59.
Cross JH. New research with diets and epilepsy. J Child Neurol 2013; 28(8): 970-4.
Woolf EC, Syed N, Scheck AC. Tumor metabolism, the ketogenic diet and beta-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy. Front Mol Neurosci 2016; 9: 122.
Gulyaeva LF, Kushlinskiy NE. Regulatory mechanisms of microRNA expression. J Transl Med 2016; 14(1): 143.
McNaughton SA, Danaher J, Russell AP. Diet and microRNA expression: a systematic review. FASEB J 2017; 31(Suppl. 1): 644-3.
Rothman KJ. BMI-related errors in the measurement of obesity. Int J Obes(Lond) 2008; 32(Suppl. 3): S56-9.
Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ 2011; 183(14): E1059-66.
Norman K, Stobaus N, Pirlich M, Bosy-Westphal A. Bioelectrical phase angle and impedance vector analysis--clinical relevance and applicability of impedance parameters. Clin Nutr 2012; 31(6): 854-61.
Veldman-Jones MH, Brant R, Rooney C, et al. Evaluating robustness and sensitivity of the nanostring technologies ncounter platform to enable multiplexed gene expression analysis of clinical samples. Cancer Res 2015; 75(13): 2587-93.
Cione E, Gallelli L. Direct detection of circulating microRNAs unveiled the absence of microRNA-218-5p in smoker subjects. Am J Respir Crit Care Med 2017; 196(4): 532.
https: // (Accessed on Oct 11, 2017).
Geiss GK, Bumgarner RE, Birditt B, et al. Direct multiplexed measurement of gene expression with color-coded probe pairs. Nat Biotechnol 2008; 26(3): 317-25.
Waggott D, Chu K, Yin S, Wouters BG, Liu FF, Boutros PC. NanoStringNorm: an extensible R package for the pre-processing of nanostring mRNA and miRNA data. Bioinformatics 2012; 28(11): 1546-8.
Shkurnikov MY, Knyazev EN, Fomicheva KA, et al. Analysis of plasma microRNA associated with hemolysis. Bull Exp Biol Med 2016; 160(6): 748-50.
Goday A, Bellido D, Sajoux I, et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes 2016; 6(9): e230.
Rahman M, Muhammad S, Khan MA, et al. The beta-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages. Nat Commun 2014; 5: 3944.
Offermanns S. Hydroxy-carboxylic acid receptor actions in metabolism. Trends Endocrinol Metab 2017; 28(3): 227-36.
Murray AJ, Knight NS, Cole MA, et al. Novel ketone diet enhances physical and cognitive performance. FASEB J 2016; 30(12): 4021-32.
Maiorana A, Manganozzi L, Barbetti F, et al. Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damage. Orphanet J Rare Dis 2015; 10: 120.
Safar FH, Mojiminiyi OA, Al-Rumaih HM, Diejomaoh MF. Computational methods are significant determinants of the associations and definitions of insulin resistance using the homeostasis model assessment in women of reproductive age. Clin Chem 2011; 57(2): 279-85.
Foster DW. Insulin resistance--a secret killer? N Engl J Med 1989; 320(11): 733-4.
Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: underlying causes and modification by exercise training. Compr Physiol 2013; 3(1): 1-58.
Tirosh A, Golan R, Harman-Boehm I, et al. Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial. Diabetes Care 2013; 36(8): 2225-32.
Tome-Carneiro J, Larrosa M, Yanez-Gascon MJ, et al. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res 2013; 72: 69-82.
Ryu MS, Langkamp-Henken B, Chang SM, Shankar MN, Cousins RJ. Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis. Proc Natl Acad Sci USA 2011; 108(52): 20970-5.
Merra G, Gratteri S, De Lorenzo A, et al. Effects of very-low-calorie diet on body composition, metabolic state, and genes expression: a randomized double-blind placebo-controlled trial. Eur Rev Med Pharmacol Sci 2017; 21(2): 329-45.
Pogribny IP. MicroRNAs as biomarkers for clinical studies. Exp Biol Med (Maywood) 2018; 243(3): 283-90.
Yu D, Wu L, Gill P, et al. Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol 2018; 92(2): 845-58.
Brandhorst S, Choi IY, Wei M, et al. A periodic diet that mimics fasting promotes multi-system regeneration, enhanced cognitive performance, and healthspan. Cell Metab 2015; 22(1): 86-99.
Tsang HF, Xue VW, Koh SP, Chiu YM, Ng LP, Wong SC. NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics. Expert Rev Mol Diagn 2017; 17(1): 95-103.
Nielsen T, Wallden B, Schaper C, et al. Analytical validation of the PAM50-based prosigna breast cancer prognostic gene signature assay and ncounter analysis system using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer 2014; 14: 177.
Dweep H, Sticht C, Pandey P, Gretz N. miRWalk--database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform 2011; 44(5): 839-47.
Hamberg M, Backes C, Fehlmann T, et al. MiR Target Link--miRNAs, genes and interaction networks. Int J Mol Sci 2016; 17(4): 564.
Pizzamiglio S, Zanutto S, Ciniselli CM, et al. A methodological procedure for evaluating the impact of hemolysis on circulating microRNAs. Oncol Lett 2017; 13(1): 315-20.
Ameling S, Kacprowski T, Chilukoti RK, et al. Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study. BMC Med Genomics 2015; 8: 61.
Jiang S, Yan W, Wang SE, Baltimore D. Let-7 suppresses B cell activation through restricting the availability of necessary nutrients. Cell Metab 2018; 27(2): 393-403.e4.
Dumortier O, Hinault C, Van Obberghen E. MicroRNAs and metabolism crosstalk in energy homeostasis. Cell Metab 2013; 18(3): 312-24.
Redis RS, Calin GA. SnapShot: non-coding RNAs and metabolism. Cell Metab 2017; 25(1): 220-e1.
Miyazaki S, Taniguchi H, Moritoh Y, et al. Nuclear hormone Retinoid X Receptor (RXR) negatively regulates the glucose-stimulated insulin secretion of pancreatic ss-cells. Diabetes 2010; 59(11): 2854-61.
Kane MA, Folias AE, Pingitore A, et al. Identification of 9-cis-retinoic acid as a pancreas-specific autacoid that attenuates glucose-stimulated insulin secretion. Proc Natl Acad Sci USA 2010; 107(50): 21884-9.
Ikink GJ, Boer M, Bakker ER, Hilkens J. IRS4 induces mammary tumorigenesis and confers resistance to HER2-targeted therapy through constitutive PI3K/AKT-pathway hyperactivation. Nat Commun 2016; 7: 13567.
Ikink GJ, Hilkens J. Insulin receptor substrate 4 (IRS4) is a constitutive active oncogenic driver collaborating with HER2 and causing therapeutic resistance. Mol Cell Oncol 2017; 4(2): e1279722.
Maurer GD, Brucker DP, Bahr O, et al. Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy. BMC Cancer 2011; 11: 315.
Stafford P, Abdelwahab MG, Kim DY, Preul MC, Rho JM, Scheck AC. The ketogenic diet reverses gene expression patterns and reduces reactive oxygen species levels when used as an adjuvant therapy for glioma. Nutr Metab 2010; 7: 74.
Chung HY, Park YK. Rationale, feasibility and acceptability of ketogenic diet for cancer treatment. J Cancer Prev 2017; 22(3): 127-34.
Lee C, Raffaghello L, Brandhorst S, et al. Fasting cycles retard growth of tumors and sensitize a range of cancer cell types to chemotherapySci Translat Med 2012; 4(124): 124ra27
He Z, Yi J, Liu X, et al. MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. Mol Cancer 2016; 15(1): 51.
http: // (Accessed on Feb 15, 2018).
Laxer KD, Trinka E, Hirsch LJ, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav 2014; 37: 59-70.
Kossoff EH, Zupec-Kania BA, Amark PE, et al. Optimal clinical management of children receiving the ketogenic diet: recommendations of the international ketogenic diet study group. Epilepsia 2009; 50(2): 304-17.
Urbain P, Bertz H. Monitoring for compliance with a ketogenic diet: what is the best time of day to test for urinary ketosis? Nutr Metab 2016; 13: 77.

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