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Abstract Details
Trimethylamine N-Oxide levels are associated with NASH in obese subjects with type 2 diabetes
Diabetes Metab. 2020 Aug 10;S1262-3636(20)30102-6. doi: 10.1016/j.diabet.2020.07.010.Online ahead of print.
Paola León-Mimila1, Hugo Villamil-Ramírez2, Xinmin S Li3, Diana M Shih1, Simon T Hui1, Elvira Ocampo-Medina2, Blanca López-Contreras2, Sofía Morán-Ramos4, Marisol Olivares-Arevalo2, Paula Grandini-Rosales2, Luis Macías-Kauffer2, Israel González-González5, Rogelio Hernández-Pando6, Francisco Gómez-Pérez7, Francisco Campos-Pérez5, Carlos Aguilar-Salinas8, Elena Larrieta-Carrasco9, Teresa Villarreal-Molina10, Zeneng Wang3, Aldons J Lusis1, Stanley L Hazen11, Adriana Huertas-Vazquez12, Samuel Canizales-Quinteros13
Author information
1Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA.
2Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico.
3Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
4Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico; Cátedras, CONACyT, Mexico City, Mexico.
5Clínica Integral de Cirugía para la Obesidad y Enfermedades Metabólicas, Hospital General Dr. Rubén Lénero, Mexico City, Mexico.
6Departamento de Patología Experimental, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City, Mexico.
7Departamento de Endocrinología, INCMNSZ, Mexico City, Mexico.
8Departamento 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.
9Departamento de Gastroenterología, INCMNSZ, Mexico City, Mexico.
10Laboratorio de Enfermedades Cardiovasculares, INMEGEN, Mexico City, Mexico.
11Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA; Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA.
12Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, USA. Electronic address: adrianahuertasv@gmail.com.
13Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM/INMEGEN, Mexico City, Mexico. Electronic address: cani@unam.mx.
Abstract
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 insulin resistance. 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.