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Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.
Izquierdo, Andrea G; Carreira, Marcos C; Boughanem, Hatim; Moreno-Navarrete, Jose M; Nicoletti, Carolina F; Oliver, Paula; de Luis, Daniel; Nonino, Carla B; Portillo, Maria P; Martinez-Olmos, Miguel A; Fernandez-Real, Jose M; Tinahones, Francisco J; Martinez, J Alfredo; Macias-González, Manuel; Casanueva, Felipe F; Crujeiras, Ana B.
Afiliación
  • Izquierdo AG; Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), Santiago de Compostela, Spain.
  • Carreira MC; Endocrine Division, Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.
  • Boughanem H; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
  • Moreno-Navarrete JM; Endocrine Division, Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.
  • Nicoletti CF; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
  • Oliver P; Molecular Endocrinology Group, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain.
  • de Luis D; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
  • Nonino CB; Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, University of Malaga (IBIMA), Malaga, Spain.
  • Portillo MP; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
  • Martinez-Olmos MA; Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona (IdIBGi) and Universitat de Girona, Girona, Spain.
  • Fernandez-Real JM; Department of Internal Medicine, Laboratory of Nutrigenomic Studies, Ribeirao Preto Medical School (FMRP) University of Sao Paulo (USP), Sao Paulo, Brazil.
  • Tinahones FJ; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
  • Martinez JA; Nutrigenomics and Obesity Group, University of the Balearic Islands and Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
  • Macias-González M; Center of Investigation of Endocrinology and Nutrition, Medicine School and Department of Endocrinology and Investigation, Hospital Clinico Universitario, University of Valladolid, Valladolid, Spain.
  • Casanueva FF; Department of Internal Medicine, Laboratory of Nutrigenomic Studies, Ribeirao Preto Medical School (FMRP) University of Sao Paulo (USP), Sao Paulo, Brazil.
  • Crujeiras AB; CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Madrid, Spain.
Eur J Clin Invest ; 52(2): e13685, 2022 Feb.
Article en En | MEDLINE | ID: mdl-34582564
BACKGROUND: Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. AIM: To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). MATERIALS AND METHODS: DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n = 32) or visceral (VAT; n = 32) adipose tissue, and PBMCs (n = 34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6 months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. RESULTS: As compared with normal weight, VAT from patients with obesity showed higher ACE2 methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. CONCLUSION: Obesity-related VAT shows hypermethylation and downregulation of the ACE2 gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucocitos Mononucleares / Grasa Intraabdominal / Grasa Subcutánea / Receptores de Coronavirus / Enzima Convertidora de Angiotensina 2 / Obesidad Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Clin Invest Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucocitos Mononucleares / Grasa Intraabdominal / Grasa Subcutánea / Receptores de Coronavirus / Enzima Convertidora de Angiotensina 2 / Obesidad Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: Eur J Clin Invest Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido