Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes
Por:
León-Mimila P., Villamil-Ramírez H., Li X.S., Shih D.M., Hui S.T., Ocampo-Medina E., López-Contreras B., Morán-Ramos S., Olivares-Arevalo M., Grandini-Rosales P., Macías-Kauffer L., González-González I., Hernández-Pando R., Gómez-Pérez F., Campos-Pérez F., Aguilar-Salinas C., Larrieta-Carrasco E., Villarreal-Molina T., Wang Z., Lusis A.J., Hazen S.L., Huertas-Vazquez A., Canizales-Quinteros S.
Publicada:
1 mar 2021
Ahead of Print:
1 ene 2020
Resumen:
Aims. - Trimethylamine N-oxide (TMAO), choline and betaine serum levels
have been associated with metabolic diseases including type 2 diabetes
(T2D) and non-alcoholic fatty liver disease (NAFLD). These associations
could be mediated by insulin resistance. However, the relationships
among these metabolites, insulin resistance and NAFLD have not been
thoroughly investigated. Moreover, it has recently been suggested that
TMAO could play a role in NAFLD by altering bile acid metabolism. We
examined the association between circulating TMAO, choline and betaine
levels and NAFLD in obese subjects.
Methods. - Serum TMAO, choline, betaine and bile acid levels were
measured in 357 Mexican obese patients with different grades of NAFLD as
determined by liver histology. Associations of NAFLD with TMAO, choline
and betaine levels were tested. Moreover, association of TMAO levels
with non-alcoholic steatohepatitis (NASH) was tested separately in
patients with and without T2D.
Results. - TMAO and choline levels were significantly associated with
NAFLD histologic features and NASH risk. While increased serum TMAO
levels were significantly associated with NASH in patients with T2D, in
non-T2D subjects this association lost significance after adjusting for
sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were
associated both with increased TMAO levels and NASH.
Conclusions. - In obese patients, circulating TMAO levels were
associated with NASH mainly in the presence of T2D. Functional studies
are required to evaluate the role of insulin resistance and T2D in this
association, both highly prevalent in NASH patients. (C) 2020 Elsevier
Masson SAS. All rights reserved.
Filiaciones:
León-Mimila P.:
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, United States
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
Villamil-Ramírez H.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
Li X.S.:
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
Shih D.M.:
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, United States
Hui S.T.:
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, United States
Ocampo-Medina E.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
López-Contreras B.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
Morán-Ramos S.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
Cátedras, CONACyT, Mexico City, Mexico
Olivares-Arevalo M.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
Grandini-Rosales P.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
Macías-Kauffer L.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
González-González I.:
Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico
Hernández-Pando R.:
Departamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico
Gómez-Pérez F.:
Departamento de Endocrinología, INCMNSZ, Mexico City, Mexico
Campos-Pérez F.:
Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico
Aguilar-Salinas C.:
Departamento de Endocrinología, INCMNSZ, Mexico City, Mexico
Unidad de Investigación en Enfermedades Metabólicas, INCMNSZ, Mexico City, Mexico
Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Monterrey, Nuevo Leon 64710, Mexico
Larrieta-Carrasco E.:
Departamento de Gastroenterología, INCMNSZ, Mexico City, Mexico
Villarreal-Molina T.:
Laboratorio de Genómica de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico
Wang Z.:
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
Lusis A.J.:
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, United States
Hazen S.L.:
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, United States
Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, United States
Huertas-Vazquez A.:
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, United States
Canizales-Quinteros S.:
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico
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