The Expression of Genes Related to Reverse Cholesterol Transport and Leptin Receptor Pathways in Peripheral Blood Mononuclear Cells Are Decreased in Morbid Obesity and Related to Liver Function

Author:

Jiménez-Cortegana Carlos1ORCID,López-Enríquez Soledad1ORCID,Alba Gonzalo1ORCID,Santa-María Consuelo2ORCID,Martín-Núñez Gracia M.3,Moreno-Ruiz Francisco J.4,Valdés Sergio56ORCID,García-Serrano Sara56,Rodríguez-Díaz Cristina7,Ho-Plágaro Ailec7,Fontalba-Romero María I.5ORCID,García-Fuentes Eduardo789ORCID,Garrido-Sánchez Lourdes310,Sánchez-Margalet Víctor111ORCID

Affiliation:

1. Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, 41009 Seville, Spain

2. Department of Biochemistry and Molecular Biology, University of Seville Pharmacy School, 41012 Seville, Spain

3. Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain

4. Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain

5. Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain

6. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 29010 Málaga, Spain

7. Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain

8. CIBER Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, 29010 Málaga, Spain

9. Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain

10. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 29010 Málaga, Spain

11. Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/Virgen Macarena, CSIC, Universidad de Sevilla, 41013 Seville, Spain

Abstract

Obesity is frequently accompanied by non-alcoholic fatty liver disease (NAFLD). These two diseases are associated with altered lipid metabolism, in which reverse cholesterol transport (LXRα/ABCA1/ABCG1) and leptin response (leptin receptor (Ob-Rb)/Sam68) are involved. The two pathways were evaluated in peripheral blood mononuclear cells (PBMCs) from 86 patients with morbid obesity (MO) before and six months after Roux-en-Y gastric bypass (RYGB) and 38 non-obese subjects. In the LXRα pathway, LXRα, ABCA1, and ABCG1 mRNA expressions were decreased in MO compared to non-obese subjects (p < 0.001, respectively). Ob-Rb was decreased (p < 0.001), whereas Sam68 was increased (p < 0.001) in MO. RYGB did not change mRNA gene expressions. In the MO group, the LXRα pathway (LXRα/ABCA1/ABCG1) negatively correlated with obesity-related variables (weight, body mass index, and hip), inflammation (C-reactive protein), and liver function (alanine-aminotransferase, alkaline phosphatase, and fatty liver index), and positively with serum albumin. In the Ob-R pathway, Ob-Rb and Sam68 negatively correlated with alanine-aminotransferase and positively with albumin. The alteration of LXRα and Ob-R pathways may play an important role in NAFLD development in MO. It is possible that MO patients may require more than 6 months following RYBGB to normalize gene expression related to reverse cholesterol transport or leptin responsiveness.

Funder

Instituto de Salud Carlos III

Consejería de Salud y Familias

Consejería de Universidad, Investigación e Innovación

European Regional Development Fund

Margarita Salas Fellowship

Consejería de Transformación Económica, Industria, Conocimiento y Universidades de la Junta de Andalucía

Nicolas Monardes program from the Consejería de Salud de Andalucía

Publisher

MDPI AG

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