Central obesity is characterized by low-grade chronic inflammation that is mirrored by alterations of the microenvironment of the visceral adipose tissue. The objective of the present study is to explore the effects of different eating,sleeping, and physical activity pattern and dietary regimens i.e. low-calorie ketogenic diet (LCKD) and low-calorie balanced nonketogenic diet (LCD) - in obese patients proposed for diet therapy or bariatric surgery (Sleeve Gastrectomy) on inflammatory (ESR, CRP, ferritin, white blood cells count ), immunitary (AntiSARS-CoV-2 IgG and IgM, Cell mediated response to SARS CoV-2, lymphocyte and monocyte subpopulations, cytokines) and metabolic (glucose, insulin, lipid profile) indices, on circulating PBMC (peripheral blood mononuclear cells) gene expression Furthermore, in patients undergoing bariatric surgery, the morpho-functional characteristics of the visceral adipose tissue and the polarization of the resident macrophages will be analyzed. The results of this study will allow to define the characteristics of the immune-inflammatory derangement of complicated obesity and to identify therapeutic targets and strategic paths related to the immuno-metabolic aspects closely related to the visceral obesity phenotype that predispose to severe forms of COVID 19. These investigations will provide a detailed and mechanistic evaluation of the effects of different types of eating, sleeping and physical activity pattern (with particular attention to KD), and of bariatric surgery on inflammatory, metabolic and body composition parameters. The comparative study of tissue macrophage polarization with lymphocyte subpopulations and the typing and gene expression of circulating monocytes will provide information on the potential role of monocytes as peripheral indicators of adipose tissue alterations and of therapeutic efficacy
The results of this study will allow us to deepen our knowledge on the etiological factors of the chronic inflammatory and dys-metabolic state of obesity and to provide a detailed and mechanistic evaluation of the effects of the different types of diet, with particular attention to the ketogenic diet, and of bariatric surgery on immunological (innate and adaptive), inflammatory, metabolic and body composition parameters that predispose to COVID-19 severity and that influence immunological response to SARS-CoV2 disease or vaccination.
Tissue analysis together with peripheral blood analysis will provide important data to understand the mechanisms of pro-inflammatory and metabolic alterations that underlie pro-inflammatory feedforward loop of cytokines on innate immune cells resulting in cytokine storm, coagulopathy, and acute respiratory distress syndrome (ARDS). In particular, we will be able to clarify:
1) the correlations between morpho-functional characteristics of the visceral adipose tissue of the obese (size of adipocytes: hypertrophic adipocytes cause a hypoxic-inflammatory state; expression of cytokines and adipokines; expression of "brown", "beige" adipocyte differentiation markers, and "white") and the polarization of macrophages in the same district, obtaining important information on the mechanisms of the altered inflammatory response of the obese visceral tissue;
2) if the tissue characteristics correlate with plasmatic inflammatory and metabolic parameters and with the typing/gene expression of circulating monocytes, helping to clarify important mechanisms responsible for the chronic state of low-grade inflammation and morbidity of the obese.
3) if and how tissue and plasma changes can be influenced by bariatric surgery, and by the dietary regime, suggesting the possibility of choosing preferential therapeutic strategies;
4) the comparative study of the typing of the circulating monocytes with that of the polarization of the tissue macrophages and the microenvironment of the visceral tissue, in basal conditions and after the dietary treatments will allow us to define the potential of the circulating monocytes as mirrors of tissue alterations and as markers of response to various therapies;
5) The results of the clinical follow-up of patients in the short, medium and long term will be able to provide indications on the treatment of choice, among those evaluated, able to obtain and maintain over time the improvement in the body fat distribution and in the metabolic-inflammatory component
BIBLIOGRAPHY
Andersen CJ, et al Adv Nutr. 2016;7(1):66-75. Epub 2016/01/17
Barrea L et al . J Transl Med. 2020;18(1):318. doi: 10.1186/s12967-020-02465-y.
Briguglio M et al Front Med. 2020;7:146. doi: 10.3389/fmed.2020.00146
Caprio M et al J Endocrinol Invest. 2019 May 20. doi: 10.1007/s40618-019-01061-2
Cinkajzlová A, et al, Physiol Res.2017, 22;66(4):641-652. Epub2017 Apr 12De Girolamo. et al .Int J ImmunopatholPharmacol, 2013, 1S: 11-21
Doumouras AG , et al . Ann Intern Med. 2020;173:694-703.
Elliot JG et al. Eur Respir J 2019; 54(6).Forsythe Ce et al, Lipids, 2008, 43:65¿77
Foster DJ et al. Am J Physiol Lung Cell Mol Physiol 2010; 298(3): L392-403.
Gangitano E et al Nutrients. 2021 Mar 20;13(3):1004.
Genco A et al , Obes Surg. 2018, Dec;28(12):3733-3737
Genco A et al , SurgEndosc. 2015, Aug;29(8):2339-43
Genco Aet al , . Obes Surg. 2018, Feb;28(2):405-409.
Huang C et al. Lancet 2020; 395(10223): 497-506.
Kornberg MD et al Wiley Interdiscip Rev Syst Biol Med . 2020 Feb 27;e1486 doi: 10.1002/wsbm.1486.
Lubrano C et al Int J Obes (Lond). 2010 Sep;34(9):1404-14. doi: 10.1038/ijo.2010.54.
Lubrano C et al. https://www.bmj.com/content/368/bmj.m627/rapid-responses 2020
Lubrano C, et al PLoS One. 2012,7(10):e47059
MacDaragh Ryan P Obesity 2020 in press doi.org/10.1002/oby.22843
Mariani S, et al, Endocrine. 2017, Sep;57(3):455-463.
Mattioli AV et al . Nutr Metab Cardiovasc Dis. 2020;30(9):1409¿1417. doi: 10.1016/j.numecd.2020.05.020
Nakajima A et al, PLoS One 2017; 12 (7): e0179696
Neidich SD Int J Obes (Lond). 2017;41(9):1324-30. Epub 2017/06/07
Norbert S Nature Rev Endocrinol 2020 16 341-2
Pecht T et al, PloS One 2016, Jul 21;11(7):e0159350.
Petrangeli.et al J Cell Physiol. 2016, Mar;231(3):668-79.
Pinto A et al, Antioxidants, 2018, 7, 63; doi:10.3390
Poggiogalle E et al 2016 Eat Weight Disord. 2016 Sep;21(3):501-505. doi: 10.1007/s40519-016-0254-
Poggiogalle E, et al..ClinNutr. 2019, Feb 10. pii: S0261-5614(19)30062-7
Poggiogalle E,. Clin Nutr. 2019 Oct;38(5):2430-2435. doi: 10.1016/j.clnu.2019.01.028.
Poitou C, et al, .Arterioscler Thromb Vasc Biol. 2011, Oct;31(10):2322-30.
Rubini A et al Lung. 2015 Dec;193(6):939-45
Watanabe M, et al. Metabolism. 2020;111:154319. Epub 2020/07/28.
Youm YH et al Nat Med. 2015;21(3):263-9. Epub 2015/02/17. doi: 10.1038/nm.3804