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Laparoscopic sleeve gastrectomy induces molecular changes in peripheral white blood cells.

Department of Surgery, Hospital del Mar, Barcelona, Spain; Centre de Recerca Experimental Biomèdica Aplicada (CREBA), Lleida, Spain. Electronic address: mbeisani@gmail.com. Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Badalona, Spain. Electronic address: spabmc@ibmb.csic.es. Department of Surgery, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain. Electronic address: paumorenos@gmail.com. Endocrinology and Nutrition Service, Department of Medicine, Universitat Autònoma de Barcelona, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain. Electronic address: emarlo78@gmail.com. Department of Surgery, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain. Electronic address: jtarasco@hotmail.com. Clinical Biochemistry Service, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain. Electronic address: mgranada.germanstrias@gencat.cat. Endocrinology and Nutrition Service, Department of Medicine, Universitat Autònoma de Barcelona, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain. Electronic address: ropuig@gmail.com. Department of Surgery, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain. Electronic address: lolo_cremades@hotmail.com. Endocrinology and Nutrition Service, Department of Medicine, Universitat Autònoma de Barcelona, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain; CIBER de Enfermedades Raras (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: mpuigd@igtp.cat. Program of Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Badalona, Spain. Electronic address: mjorda@igtp.cat. Endocrinology and Nutrition Service, Department of Medicine, Universitat Autònoma de Barcelona, Germans Trias i Pujol University, Hospital and Research Institute, Badalona, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: spelli75@gmail.com. Endocrine, Metabolic and Bariatric Surgery Unit (EAC-BS Center of Excellence), Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: balibrea@gmail.com.

Clinical nutrition (Edinburgh, Scotland). 2020;(2):592-598
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Abstract

BACKGROUND & AIMS Peripheral white blood cells (PWBC) may allow for the development of obesity biomarkers. We aimed to investigate the existence of gene expression and DNA methylation changes in PWBC after a very low calorie diet (VLCD) followed by a laparoscopic sleeve gastrectomy (LSG), and its correlation with surgical outcomes. METHODS From July 2013 to June 2014, 35 consecutive bariatric patients and 33 healthy lean volunteers were recruited. Molecular data was obtained once on the control group and at 3 different times on the LSG group: 1) at baseline; 2) after 2 weeks of VLCD, right before LSG; and 3) 6 months after LSG. The expression of 12 genes in PWBC was analyzed by quantitative real-time polymerase chain reaction: ghrelin (GHRL), visfatin (NAMPT), insulin receptor substrate 1 (IRS1), fat mass and obesity-related gene (FTO), leptin (LEP), peroxisome proliferator-activated receptor gamma (PPARG), adiponectin (ADIPOQ), fatty acid synthase (FASN), melanocortin 4 receptor (MC4R), fas cell surface death receptor (FAS), tumor necrosis factor alpha (TNF) and chemokine (C-C motif) ligand 2 (CCL2). Moreover, DNA methylation of GHRL, NAMPT and FAS promoters was analyzed in PWBC by bisulfite pyrosequencing. RESULTS Seven genes (GHRL, NAMPT, IRS1, FTO, FAS, TNF and CCL2) had detectable expression in PWBC. FTO expression at baseline was lower in patients than in controls (p = 0.042), equalizing after LSG. In patients, FAS expression decreased after VLCD (p = 0.01) and stayed low after LSG (p = 0.015). Also, CCL2 expression decreased 50% after LSG compared to pre-surgical levels (p = 0.016). All studied CpG sites in the GHRL gene promoter followed a consistent pattern of DNA methylation/demethylation. No direct correlation between these molecular changes and surgical outcomes was found at 1-year follow-up. CONCLUSIONS FTO expression increased and FAS and CCL2 expression decreased in PWBC after LSG. Molecular changes did not correlate with surgical outcomes.