title: The expression of genes involved in jejunal lipogenesis and lipoprotein synthesis is altered in morbidly obese subjects with insulin resistance.
abstract: The dyslipidemia associated with type 2 diabetes mellitus (T2DM) is an important risk factor for atherosclerotic cardiovascular disease. However, until now little attention has been paid to the role that the intestine might have. The aim of this research was to determine the relation between insulin resistance and intestinal de novo lipogenesis/lipoprotein synthesis in morbidly obese subjects and to study the effect of insulin on these processes. Jejunal mRNA expression of the different genes involved in the intestinal de novo lipogenesis/lipoprotein synthesis was analyzed in three groups of morbidly obese subjects: Group 1 with low insulin resistance (MO-low-IR), group 2 with high insulin resistance (MO-high-IR), and group 3 with T2DM and treatment with metformin (MO-metf-T2DM). In addition, intestinal epithelial cells (IECs) from MO-low-IR were incubated with different doses of insulin/glucose. In Group 2 (MO-high-IR), the jejunal mRNA expression levels of apo A-IV, ATP-citrate lyase (ACLY), pyruvate dehydrogenase (lipoamide) beta (PDHB), and sterol regulatory element-binding protein-1c (SREBP-1c) were significantly higher and acetyl-CoA carboxylase alpha (ACC1) and fatty-acid synthase lower than in Group 1 (MO-low-IR). In Group 3 (MO-metf-T2DM), only the ACLY and PDHB mRNA expressions were significantly higher than in Group 1 (MO-low-IR). The mRNA expression of most of the genes studied was significantly linked to insulin and glucose levels. The incubation of IEC with different doses of insulin and glucose produced a higher expression of diacylglycerol acyltransferase 2, microsomal triglyceride transfer protein, apo A-IV, SREBP-1c, and ACC1 when both, glucose and insulin, were at a high concentration. However, with only high insulin levels, there were higher apo A-IV, PDHB and SREBP-1c expressions, and a lower ACLY expression. In conclusion, the jejunum of MO-high-IR has a decreased mRNA expression of genes involved in de novo fatty-acid synthesis and an increase of genes involved in acetyl-CoA and lipoprotein synthesis. This effect is attenuated by metformin. In addition, the expression of most of the genes studied was found to be regulated by insulin.
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gutierrez-Repiso
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.|CIBERDEM, Instituto de Salud Carlos III, Málaga, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Rodriguez-Pacheco
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Garcia-Arnes
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.|CIBERDEM, Instituto de Salud Carlos III, Málaga, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Valdes
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Gonzalo
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.|CIBERDEM, Instituto de Salud Carlos III, Málaga, Spain.|CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Soriguer
authors.affiliation: Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario, Málaga, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Moreno-Ruiz
authors.affiliation: Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario, Málaga, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Rodriguez-Cañete
authors.affiliation: Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario, Málaga, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Gallego-Perales
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Alcain-Martinez
authors.affiliation: Unidad de Gestión Clínica de Aparato Digestivo, Hospital Regional Universitario, Málaga, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Vazquez-Pedreño
authors.affiliation: Departamento de Bioquímica Médica, Biología Molecular e Inmunología, Facultad de Medicina, Universidad de Sevilla, Sevilla, Spain.|CABIMER-Centro de Biología Molecular y Medicina Regenerativa (CSIC-Universidad de Sevilla-UPO-Junta de Andalucia), Sevilla, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Lopez-Enriquez
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Regional Universitario/Universidad de Málaga, Málaga, Spain.|CIBERDEM, Instituto de Salud Carlos III, Málaga, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Garcia-Serrano
authors.affiliation: CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain.|Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Garrido-Sanchez
authors.affiliation: CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain.|Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Garcia-Fuentes
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007333:Insulin Resistance; D007583:Jejunum / Q000378:metabolism*; D050155:Lipogenesis / Q000235:genetics*; D008074:Lipoproteins / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D008074:Lipoproteins; D012333:RNA, Messenger