{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:55:29Z","timestamp":1788566129369,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans. Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program. Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed. Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD (p = 0.02 and p &lt; 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively. Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.<\/jats:p>","DOI":"10.3390\/nu12072141","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T06:08:17Z","timestamp":1595225297000},"page":"2141","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Baseline HOMA IR and Circulating FGF21 Levels Predict NAFLD Improvement in Patients Undergoing a Low Carbohydrate Dietary Intervention for Weight Loss: A Prospective Observational Pilot Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-8814","authenticated-orcid":false,"given":"Mikiko","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Risi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1866-8223","authenticated-orcid":false,"given":"Elisabetta","family":"Camajani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savina","family":"Contini","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnese","family":"Persichetti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Tuccinardi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Diabetes, University Campus Bio-Medico of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Ernesti","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Surgical Endoscopy Unit, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1762-4701","authenticated-orcid":false,"given":"Stefania","family":"Mariani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Lubrano","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Genco","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Surgical Endoscopy Unit, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Spera","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucio","family":"Gnessi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Basciani","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrendo.2017.56","article-title":"Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance","volume":"13","author":"Meex","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.3748\/wjg.v16.i38.4773","article-title":"Hepatic steatosis, low-grade chronic inflammation and hormone\/growth factor\/adipokine imbalance","volume":"16","author":"Tarantino","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1056\/NEJMra1011035","article-title":"Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease","volume":"371","author":"Shulman","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.numecd.2010.05.005","article-title":"Ectopic fat and cardiovascular disease: What is the link?","volume":"20","author":"Gastaldelli","year":"2010","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/ajh.2012.92","article-title":"Associations between trunk, leg and total body adiposity with arterial stiffness","volume":"25","author":"Lee","year":"2012","journal-title":"Am. J. Hypertens"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20","DOI":"10.14797\/mdcj-13-1-20","article-title":"Epicardial Fat in the Maintenance of Cardiovascular Health","volume":"13","author":"Wu","year":"2017","journal-title":"Methodist. Debakey Cardiovasc. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1152\/physrev.00033.2011","article-title":"Pathophysiology of human visceral obesity: An update","volume":"93","author":"Tchernof","year":"2013","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1186\/s12944-017-0572-9","article-title":"A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease","volume":"16","author":"Chen","year":"2017","journal-title":"Lipids Health Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD development and therapeutic strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Risi, R., De Giorgi, F., Tuccinardi, D., Mariani, S., Basciani, S., Lubrano, C., Lenzi, A., and Gnessi, L. (2020). Obesity treatment within the Italian national healthcare system tertiary care centers: What can we learn?. Eat Weight Disord.","DOI":"10.1007\/s40519-020-00936-1"},{"key":"ref_11","first-page":"395","article-title":"Obstructive sleep apnea and bone mineral density in obese patients","volume":"5","author":"Mariani","year":"2012","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lonardo, A., Mantovani, A., Lugari, S., and Targher, G. (2020). Epidemiology and pathophysiology of the association between NAFLD and metabolically healthy or metabolically unhealthy obesity. Ann. Hepatol.","DOI":"10.1016\/j.aohep.2020.03.001"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11886-020-1273-y","article-title":"Association Between Obesity and Cardiovascular Outcomes: Updated Evidence from Meta-analysis Studies","volume":"22","author":"Dwivedi","year":"2020","journal-title":"Curr. Cardiol. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s41366-018-0076-3","article-title":"Ectopic fat obesity presents the greatest risk for incident type 2 diabetes: A population-based longitudinal study","volume":"43","author":"Okamura","year":"2019","journal-title":"Int. J. Obes. (Lond.)"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Palermo, A., Tuccinardi, D., Defeudis, G., Watanabe, M., D\u2019Onofrio, L., Lauria, A.P., Napoli, N., Pozzilli, P., and Manfrini, S. (2016). BMI and BMD: The potential interplay between obesity and bone fragility. Int. J. Environ. Res. Public Health, 13.","DOI":"10.3390\/ijerph13060544"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41415-019-0611-1","article-title":"Review of obesity and periodontitis: An epidemiological view","volume":"227","author":"Arboleda","year":"2019","journal-title":"Br. Dent J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver, European Association for the Study of Diabetes, and European Association for the Study of Obesity (2016). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J. Hepatol., 64, 1388\u20131402.","DOI":"10.1016\/j.jhep.2015.11.004"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2018.12.036","article-title":"Noninvasive Assessment of Liver Disease in Patients With Nonalcoholic Fatty Liver Disease","volume":"156","author":"Castera","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1016\/j.cgh.2017.10.037","article-title":"Association Between Obesity and Discordance in Fibrosis Stage Determination by Magnetic Resonance vs Transient Elastography in Patients With Nonalcoholic Liver Disease","volume":"16","author":"Caussy","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.dld.2009.08.002","article-title":"Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease","volume":"42","author":"Lee","year":"2010","journal-title":"Dig. Liver Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s12072-016-9772-z","article-title":"Non-invasive diagnosis of hepatic steatosis","volume":"11","author":"Stern","year":"2017","journal-title":"Hepatol. Int."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Gangitano, E., Francomano, D., Addessi, E., Toscano, R., Costantini, D., Tuccinardi, D., Mariani, S., Basciani, S., and Spera, G. (2018). Mangosteen extract shows a potent insulin sensitizing effect in obese female patients: A prospective randomized controlled pilot study. Nutrients, 10.","DOI":"10.20944\/preprints201804.0049.v1"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1007\/s00535-017-1415-1","article-title":"Current and future pharmacological therapies for NAFLD\/NASH","volume":"53","author":"Sumida","year":"2018","journal-title":"J. Gastroenterol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cicero, A.F.G., Colletti, A., and Bellentani, S. (2018). Nutraceutical Approach to Non-Alcoholic Fatty Liver Disease (NAFLD): The Available Clinical Evidence. Nutrients, 10.","DOI":"10.3390\/nu10091153"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Tozzi, R., Risi, R., Tuccinardi, D., Mariani, S., Basciani, S., Spera, G., Lubrano, C., and Gnessi, L. (2020). Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature. Obes. Rev.","DOI":"10.1111\/obr.13024"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1073\/pnas.1922344117","article-title":"Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease","volume":"117","author":"Luukkonen","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1007\/s40618-019-01061-2","article-title":"Very-low-calorie ketogenic diet (VLCKD) in the management of metabolic diseases: Systematic review and consensus statement from the Italian Society of Endocrinology (SIE)","volume":"42","author":"Caprio","year":"2019","journal-title":"J. Endocrinol. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"242","DOI":"10.4103\/jpgm.JPGM_16_17","article-title":"Ketogenic diet in endocrine disorders: Current perspectives","volume":"63","author":"Gupta","year":"2017","journal-title":"J. Postgrad. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bruci, A., Tuccinardi, D., Tozzi, R., Balena, A., Santucci, S., Frontani, R., Mariani, S., Basciani, S., Spera, G., and Gnessi, L. (2020). Very low-calorie ketogenic diet: A safe and effective tool for weight loss in patients with obesity and mild kidney failure. Nutrients, 12.","DOI":"10.3390\/nu12020333"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s12020-014-0355-2","article-title":"Safety and efficacy of a multiphase dietetic protocol with meal replacements including a step with very low calorie diet","volume":"48","author":"Basciani","year":"2015","journal-title":"Endocrine"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Basciani, S., Camajani, E., Contini, S., Persichetti, A., Risi, R., Bertoldi, L., Strigari, L., Prossomariti, G., Watanabe, M., and Mariani, S. (2020). Very-Low-Calorie Ketogenic Diets with Whey, Vegetable or Animal Protein in Patients with Obesity: A Randomized Pilot Study. J. Clin. Endocrinol. Metab.","DOI":"10.1210\/clinem\/dgaa336"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s12967-019-2104-z","article-title":"The management of very low-calorie ketogenic diet in obesity outpatient clinic: A practical guide","volume":"17","author":"Muscogiuri","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"808","DOI":"10.2337\/dc15-1942","article-title":"Very Low-Calorie Diet and 6 Months of Weight Stability in Type 2 Diabetes: Pathophysiological Changes in Responders and Nonresponders","volume":"39","author":"Steven","year":"2016","journal-title":"Diabetes Care"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.cmet.2018.01.005","article-title":"An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans","volume":"27","author":"Mardinoglu","year":"2018","journal-title":"Cell. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.2337\/dc10-0856","article-title":"Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes","volume":"33","author":"Lazo","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-physiol-021115-105339","article-title":"Understanding the Physiology of FGF21","volume":"78","author":"Fisher","year":"2016","journal-title":"Annu. Rev. Physiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.cmet.2007.05.002","article-title":"Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states","volume":"5","author":"Badman","year":"2007","journal-title":"Cell. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s12020-019-02124-3","article-title":"Liver-derived FGF21 is essential for full adaptation to ketogenic diet but does not regulate glucose homeostasis","volume":"67","author":"Watanabe","year":"2020","journal-title":"Endocrine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.atherosclerosis.2020.03.009","article-title":"Relationship of fibroblast growth factor 21 levels with inflammation, lipoproteins and non-alcoholic fatty liver disease","volume":"299","author":"Tucker","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.2337\/db10-0193","article-title":"Obesity is a fibroblast growth factor 21 (FGF21)-resistant state","volume":"59","author":"Fisher","year":"2010","journal-title":"Diabetes"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"289","DOI":"10.12688\/f1000research.14117.1","article-title":"Defining \u201cFGF21 Resistance\u201d during obesity: Controversy, criteria and unresolved questions","volume":"7","author":"Markan","year":"2018","journal-title":"F1000Res"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4601","DOI":"10.1172\/JCI83349","article-title":"FGF21 and the late adaptive response to starvation in humans","volume":"125","author":"Fazeli","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/ijo.2017.138","article-title":"Plasma FGF21 levels in obese patients undergoing energy-restricted diets or bariatric surgery: A marker of metabolic stress?","volume":"41","author":"Crujeiras","year":"2017","journal-title":"Int. J. Obes. (Lond.)"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1002\/oby.22468","article-title":"Glucose and Lipid Homeostasis and Inflammation in Humans Following an Isocaloric Ketogenic Diet","volume":"27","author":"Rosenbaum","year":"2019","journal-title":"Obesity (Silver Spring)"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1111\/cen.12496","article-title":"Calorie restriction and Roux-en-Y gastric bypass have opposing effects on circulating FGF21 in morbidly obese subjects","volume":"81","author":"Lips","year":"2014","journal-title":"Clin. Endocrinol. (Oxf.)"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1016\/j.molmet.2017.08.004","article-title":"Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury","volume":"6","author":"Desai","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.molmet.2014.09.008","article-title":"Fructose ingestion acutely stimulates circulating FGF21 levels in humans","volume":"4","author":"Dushay","year":"2015","journal-title":"Mol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1865S","DOI":"10.1093\/jn\/130.7.1865S","article-title":"The protein digestibility-corrected amino acid score","volume":"130","author":"Schaafsma","year":"2000","journal-title":"J. Nutr."},{"key":"ref_49","unstructured":"(2017). Dietary Reference Values for Nutrients Summary Report. EFSA, 2017, e15121."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S0002-8223(95)00219-7","article-title":"Potential renal acid load of foods and its influence on urine pH","volume":"95","author":"Remer","year":"1995","journal-title":"J. Am. Diet Assoc."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Masieri, S., Costantini, D., Tozzi, R., De Giorgi, F., Gangitano, E., Tuccinardi, D., Poggiogalle, E., Mariani, S., and Basciani, S. (2018). Overweight and obese patients with nickel allergy have a worse metabolic profile compared to weight matched non-allergic individuals. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202683"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1002\/oby.20519","article-title":"Clinical utility and reproducibility of visceral adipose tissue measurements derived from dual-energy X-ray absorptiometry in White and African American adults","volume":"21","author":"Katzmarzyk","year":"2013","journal-title":"Obes. (Silver Spring)"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"380","DOI":"10.5582\/ddt.2015.01207","article-title":"Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future","volume":"9","author":"Tang","year":"2015","journal-title":"Drug Discov. Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1242\/dmm.001180","article-title":"A comprehensive definition for metabolic syndrome","volume":"2","author":"Huang","year":"2009","journal-title":"Dis. Model. Mech."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Watanabe, M., Tuccinardi, D., Ernesti, I., Basciani, S., Mariani, S., Genco, A., Manfrini, S., Lubrano, C., and Gnessi, L. (2020). Scientific evidence underlying contraindications to the ketogenic diet: An update. Obes. Rev.","DOI":"10.1111\/obr.13053"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/09637486.2016.1186157","article-title":"An observational study of sequential protein-sparing, very low-calorie ketogenic diet (Oloproteic diet) and hypocaloric Mediterranean-like diet for the treatment of obesity","volume":"67","author":"Castaldo","year":"2016","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3389\/fpsyg.2015.00027","article-title":"Ketosis, ketogenic diet and food intake control: A complex relationship","volume":"6","author":"Paoli","year":"2015","journal-title":"Front. Psychol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/oby.2006.14","article-title":"Changes in food cravings during low-calorie and very-low-calorie diets","volume":"14","author":"Martin","year":"2006","journal-title":"Obes. 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