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Plasma Proteomics Analysis Reveals Dysregulation of Complement Proteins and Inflammation in Acquired Obesity-A Study on Rare BMI-Discordant Monozygotic Twin Pairs.
Sahebekhtiari, Navid; Saraswat, Mayank; Joenväärä, Sakari; Jokinen, Riikka; Lovric, Alen; Kaye, Sanna; Mardinoglu, Adil; Rissanen, Aila; Kaprio, Jaakko; Renkonen, Risto; Pietiläinen, Kirsi H.
Afiliación
  • Sahebekhtiari N; Obesity Research Unit, Research Programs Unit, Diabetes and Obesity Research Program, University of Helsinki, 00014, Helsinki, Finland.
  • Saraswat M; Transplantation Laboratory, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
  • Joenväärä S; HUSLAB, Helsinki University Hospital, 00029, Helsinki, Finland.
  • Jokinen R; Transplantation Laboratory, Faculty of Medicine, University of Helsinki, 00014, Helsinki, Finland.
  • Lovric A; HUSLAB, Helsinki University Hospital, 00029, Helsinki, Finland.
  • Kaye S; Obesity Research Unit, Research Programs Unit, Diabetes and Obesity Research Program, University of Helsinki, 00014, Helsinki, Finland.
  • Mardinoglu A; Science for Life Laboratory, KTH-Royal Institute of Technology, 17121, Stockholm, Sweden.
  • Rissanen A; Obesity Research Unit, Research Programs Unit, Diabetes and Obesity Research Program, University of Helsinki, 00014, Helsinki, Finland.
  • Kaprio J; Science for Life Laboratory, KTH-Royal Institute of Technology, 17121, Stockholm, Sweden.
  • Renkonen R; Department of Biology and Biological Engineering, Chalmers University of Technology, 41296, Gothenburg, Sweden.
  • Pietiläinen KH; Centre for Host-Microbiome Interactions, Dental Institute, King's College London, SE19RT, London, UK.
Proteomics Clin Appl ; 13(4): e1800173, 2019 07.
Article en En | MEDLINE | ID: mdl-30688043
PURPOSE: The purpose of this study is to elucidate the effect of excess body weight and liver fat on the plasma proteome without interference from genetic variation. EXPERIMENTAL DESIGN: The effect of excess body weight is assessed in young, healthy monozygotic twins from pairs discordant for body mass index (intrapair difference (Δ) in BMI > 3 kg m-2 , n = 26) with untargeted LC-MS proteomics quantification. The effect of liver fat is interrogated via subgroup analysis of the BMI-discordant twin cohort: liver fat discordant pairs (Δliver fat > 2%, n = 12) and liver fat concordant pairs (Δliver fat < 2%, n = 14), measured by magnetic resonance spectroscopy. RESULTS: Seventy-five proteins are differentially expressed, with significant enrichment for complement and inflammatory response pathways in the heavier co-twins. The complement dysregulation is found in obesity in both the liver fat subgroups. The complement and inflammatory proteins are significantly associated with adiposity measures, insulin resistance and impaired lipids. CONCLUSIONS AND CLINICAL RELEVANCE: The early pathophysiological mechanisms in obesity are incompletely understood. It is shown that aberrant complement regulation in plasma is present in very early stages of clinically healthy obese persons, independently of liver fat and in the absence of genetic variation that typically confounds human studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Gemelos Monocigóticos / Proteínas del Sistema Complemento / Resistencia a la Insulina / Índice de Masa Corporal / Obesidad Límite: Adult / Female / Humans / Male Idioma: En Revista: Proteomics Clin Appl Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Gemelos Monocigóticos / Proteínas del Sistema Complemento / Resistencia a la Insulina / Índice de Masa Corporal / Obesidad Límite: Adult / Female / Humans / Male Idioma: En Revista: Proteomics Clin Appl Asunto de la revista: BIOQUIMICA Año: 2019 Tipo del documento: Article País de afiliación: Finlandia Pais de publicación: Alemania