E Pardina1, R Ferrer2, J Rossell1, D Ricart-Jané1, K A Méndez-Lara3,4, J A Baena-Fustegueras5, A Lecube6,7,8, J Julve3,4,8, J Peinado-Onsurbe1. 1. Departament de Bioquímica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain. 2. Unitat d'Hormones, Servei de Bioquímica, Hospital Universitari de la Vall d'Hebron, Barcelona, Spain. 3. Institut de Recerca de l'Hospital de La Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques de l'Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain. 4. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Spain. 5. Unitat de Cirurgia, Hospital Arnau de Vilanova, Lleida, Spain. 6. Departament d'Endocrinologia i Nutrició, Hospital Universitari Arnau de Vilanova, Universitat de Lleida, Lleida, Spain. 7. Unitat de Recerca en Diabetes i Metabolisme, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain. 8. CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Barcelona, Spain.
Abstract
BACKGROUND: The notion that hepatic expression of genes involved in lipid metabolism is altered in obese patients is relatively new and its relationship with hepatic steatosis and cardiometabolic alterations remains unclear. OBJECTIVE: We assessed the impact of Roux-en-Y gastric bypass surgery (RYGB) on the expression profile of genes related to metabolic syndrome in liver biopsies from morbidly obese individuals using a custom-made, focused cDNA microarray, and assessed the relationship between the expression profile and hepatic steatosis regression. MATERIALS AND METHODS: Plasma and liver samples were obtained from patients at baseline and 12 months after surgery. Samples were assayed for chemical and gene expression analyses, as appropriate. Gene expression profiles were assessed using custom-made, focused TaqMan low-density array cards. RESULTS: RYGB-induced weight loss produced a favorable reduction in fat deposits, insulin resistance (estimated by homeostasis model assessment of insulin resistance (HOMA-IR)), and plasma and hepatic lipid levels. Compared with the baseline values, the gene expression levels of key targets of lipid metabolism were significantly altered: CD36 was significantly downregulated (-40%; P=0.001), whereas APOB (+27%; P=0.032) and SCARB1 (+37%; P=0.040) were upregulated in response to surgery-induced weight reduction. We also observed a favorable reduction in the expression of the PAI1 gene (-80%; P=0.007) and a significant increase in the expression of the PPARA (+60%; P=0.014) and PPARGC1 genes (+36%; P=0.015). Notably, the relative fold decrease in the expression of the CD36 gene was directly associated with a concomitant reduction in the cholesterol (Spearman's r=0.92; P=0.001) and phospholipid (Spearman's r=0.76; P=0.04) contents in this tissue. CONCLUSIONS: For the first time, RYGB-induced weight loss was shown to promote a favorable downregulation of CD36 expression, which was proportional to a favorable reduction in the hepatic cholesterol and phospholipid contents in our morbidly obese subjects following surgery.
BACKGROUND: The notion that hepatic expression of genes involved in lipid metabolism is altered in obesepatients is relatively new and its relationship with hepatic steatosis and cardiometabolic alterations remains unclear. OBJECTIVE: We assessed the impact of Roux-en-Y gastric bypass surgery (RYGB) on the expression profile of genes related to metabolic syndrome in liver biopsies from morbidly obese individuals using a custom-made, focused cDNA microarray, and assessed the relationship between the expression profile and hepatic steatosis regression. MATERIALS AND METHODS: Plasma and liver samples were obtained from patients at baseline and 12 months after surgery. Samples were assayed for chemical and gene expression analyses, as appropriate. Gene expression profiles were assessed using custom-made, focused TaqMan low-density array cards. RESULTS: RYGB-induced weight loss produced a favorable reduction in fat deposits, insulin resistance (estimated by homeostasis model assessment of insulin resistance (HOMA-IR)), and plasma and hepatic lipid levels. Compared with the baseline values, the gene expression levels of key targets of lipid metabolism were significantly altered: CD36 was significantly downregulated (-40%; P=0.001), whereas APOB (+27%; P=0.032) and SCARB1 (+37%; P=0.040) were upregulated in response to surgery-induced weight reduction. We also observed a favorable reduction in the expression of the PAI1 gene (-80%; P=0.007) and a significant increase in the expression of the PPARA (+60%; P=0.014) and PPARGC1 genes (+36%; P=0.015). Notably, the relative fold decrease in the expression of the CD36 gene was directly associated with a concomitant reduction in the cholesterol (Spearman's r=0.92; P=0.001) and phospholipid (Spearman's r=0.76; P=0.04) contents in this tissue. CONCLUSIONS: For the first time, RYGB-induced weight loss was shown to promote a favorable downregulation of CD36 expression, which was proportional to a favorable reduction in the hepatic cholesterol and phospholipid contents in our morbidly obese subjects following surgery.
Authors: María Eugenia Miquilena-Colina; Elena Lima-Cabello; Sonia Sánchez-Campos; María Victoria García-Mediavilla; Miguel Fernández-Bermejo; Tamara Lozano-Rodríguez; Javier Vargas-Castrillón; Xabier Buqué; Begoña Ochoa; Patricia Aspichueta; Javier González-Gallego; Carmelo García-Monzón Journal: Gut Date: 2011-01-26 Impact factor: 23.059
Authors: Matteo Nicola Dario Di Minno; Antonella Tufano; Anna Rusolillo; Giovanni Di Minno; Giovanni Tarantino Journal: World J Gastroenterol Date: 2010-12-28 Impact factor: 5.742
Authors: Dario Greco; Anna Kotronen; Jukka Westerbacka; Oscar Puig; Perttu Arkkila; Tuula Kiviluoto; Saara Laitinen; Maria Kolak; Rachel M Fisher; Anders Hamsten; Petri Auvinen; Hannele Yki-Järvinen Journal: Am J Physiol Gastrointest Liver Physiol Date: 2008-04-03 Impact factor: 4.052
Authors: Eva Pardina; Roser Ferrer; Joaquín Rivero; Juan A Baena-Fustegueras; Albert Lecube; Jose M Fort; Víctor Vargas; Roberto Catalán; Julia Peinado-Onsurbe Journal: Obesity (Silver Spring) Date: 2011-12-22 Impact factor: 5.002
Authors: Roser Ferrer; Eva Pardina; Joana Rossell; Juan Antonio Baena-Fustegueras; Albert Lecube; José María Balibrea; Enric Caubet; Oscar González; Ramón Vilallonga; Jose Manuel Fort; Julia Peinado-Onsurbe Journal: Obesity (Silver Spring) Date: 2014-08-06 Impact factor: 5.002
Authors: Eva Pardina; Juan A Baena-Fustegueras; Rafael Llamas; Roberto Catalán; Rosa Galard; Albert Lecube; Jose M Fort; Miquel Llobera; Helena Allende; Víctor Vargas; Julia Peinado-Onsurbe Journal: Obes Surg Date: 2009-03-20 Impact factor: 4.129
Authors: Gillian L Fell; Bennet S Cho; Duy T Dao; Lorenzo Anez-Bustillos; Meredith A Baker; Prathima Nandivada; Amy Pan; Alison A O'Loughlin; Paul D Mitchell; Vania Nose; Kathleen M Gura; Mark Puder Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2019-03-05 Impact factor: 4.006
Authors: Karen Alejandra Méndez-Lara; Núria Farré; David Santos; Andrea Rivas-Urbina; Jari Metso; José Luis Sánchez-Quesada; Vicenta Llorente-Cortes; Teresa L Errico; Enrique Lerma; Matti Jauhiainen; Jesús M Martín-Campos; Núria Alonso; Joan Carles Escolà-Gil; Francisco Blanco-Vaca; Josep Julve Journal: Int J Mol Sci Date: 2019-02-02 Impact factor: 5.923
Authors: Linda S May-Zhang; Zhongyi Chen; Noura S Dosoky; Patricia G Yancey; Kelli L Boyd; Alyssa H Hasty; MacRae F Linton; Sean S Davies Journal: Sci Rep Date: 2019-01-23 Impact factor: 4.379
Authors: Antonio Gázquez; María Sánchez-Campillo; Alejandro Barranco; Ricardo Rueda; Jia P Chan; Matthew J Kuchan; Elvira Larqué Journal: Front Nutr Date: 2022-04-12
Authors: Margaret A Stefater; Julian A Pacheco; Kevin Bullock; Kerry Pierce; Amy Deik; Enju Liu; Clary Clish; Nicholas Stylopoulos Journal: J Endocr Soc Date: 2020-01-23