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Open AccessArticle

Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System, Visceral Adipose Tissue, and ROS Production

Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
Department of Medical, Surgical and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy
Department of History, Society and Studies on Humanity, University of Salento, 73100 Lecce, Italy
Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
CEINGE Biotecnologie Avanzate S.C. a r.l., 80131 Napoli, Italy
Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80100 Naples, Italy
Department of Experimental Medicine, Section of Human Physiology and Unit of Dietetics and Sports Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80100 Naples, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2019, 8(12), 643;
Received: 16 November 2019 / Revised: 11 December 2019 / Accepted: 11 December 2019 / Published: 13 December 2019
Background: Caloric restriction is a valid strategy to reduce the visceral adipose tissue (VAT) content in obese persons. Hypocretin-1 (orexin-A) is a neuropeptide synthesized in the lateral hypothalamus that strongly modulates food intake, thus influencing adipose tissue accumulation. Therapeutic diets in obesity treatment may combine the advantages of caloric restriction and dietary ketosis. The current study aimed to evaluate the effect of a very low calorie ketogenic diet (VLCKD) in a population of obese patients. Methods: Adiposity parameters and orexin-A serum profiling were quantified over an 8 week period. The effect of the VLCKD on reactive oxygen species (ROS) production and cell viability was evaluated, in vitro, by culturing Hep-G2 cells in the presence of VLCKD sera. Results: Dietary intervention induced significant effects on body weight, adiposity, and blood chemistry parameters. Moreover, a selective reduction in VAT was measured by dual-energy X-ray absorptiometry. Orexin-A levels significantly increased after dietary treatment. Hep-G2 cell viability was not affected after 24, 48, and 72 h incubation with patients’ sera, before and after the VLCKD. In the same model system, ROS production was not significantly influenced by dietary treatment. Conclusion: The VLCKD exerts a positive effect on VAT decrease, ameliorating adiposity and blood chemistry parameters. Furthermore, short-term mild dietary ketosis does not appear to have a cytotoxic effect, nor does it represent a factor capable of increasing oxidative stress. Finally, to the best of our knowledge, this is the first study that shows an effect of the VLCKD upon the orexinergic system, supporting the usefulness of such a therapeutic intervention in promoting obesity reduction in the individual burden of this disease. View Full-Text
Keywords: VLCK diet; orexin-A; visceral adipose tissue VLCK diet; orexin-A; visceral adipose tissue
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Valenzano, A.; Polito, R.; Trimigno, V.; Di Palma, A.; Moscatelli, F.; Corso, G.; Sessa, F.; Salerno, M.; Montana, A.; Di Nunno, N.; Astuto, M.; Daniele, A.; Carotenuto, M.; Messina, G.; Cibelli, G.; Monda, V. Effects of Very Low Calorie Ketogenic Diet on the Orexinergic System, Visceral Adipose Tissue, and ROS Production. Antioxidants 2019, 8, 643.

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