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Genome-Wide Association Study of Diabetogenic Adipose Morphology in the GENetics of Adipocyte Lipolysis (GENiAL) Cohort.
Lundbäck, Veroniqa; Kulyté, Agné; Arner, Peter; Strawbridge, Rona J; Dahlman, Ingrid.
Afiliación
  • Lundbäck V; Lipid laboratory, Endocrinology Unit, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Kulyté A; Lipid laboratory, Endocrinology Unit, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Arner P; Lipid laboratory, Endocrinology Unit, Department of Medicine Huddinge, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • Strawbridge RJ; Institute of Health and Wellbeing, University of Glasgow, College of Medicine, Veterinarian and Life Sciences, G12 8RZ Glasgow, UK.
  • Dahlman I; Department of Medicine Solna, Karolinska Institutet, 171 77 Stockholm, Sweden.
Cells ; 9(5)2020 04 27.
Article en En | MEDLINE | ID: mdl-32349335
An increased adipocyte size relative to the size of fat depots, also denoted hypertrophic adipose morphology, is a strong risk factor for the future development of insulin resistance and type 2 diabetes. The regulation of adipose morphology is poorly understood. We set out to identify genetic loci associated with adipose morphology and functionally evaluate candidate genes for impact on adipocyte development. We performed a genome-wide association study (GWAS) in the unique GENetics of Adipocyte Lipolysis (GENiAL) cohort comprising 948 participants who have undergone abdominal subcutaneous adipose biopsy with a determination of average adipose volume and morphology. The GWAS identified 31 genetic loci displaying suggestive association with adipose morphology. Functional evaluation of candidate genes by small interfering RNAs (siRNA)-mediated knockdown in adipose-derived precursor cells identified six genes controlling adipocyte renewal and differentiation, and thus of potential importance for adipose hypertrophy. In conclusion, genetic and functional studies implicate a regulatory role for ATL2, ARHGEF10, CYP1B1, TMEM200A, C17orf51, and L3MBTL3 in adipose morphology by their impact on adipogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Diabetes Mellitus Tipo 2 / Obesidad Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Cells Año: 2020 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adipocitos / Diabetes Mellitus Tipo 2 / Obesidad Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Cells Año: 2020 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Suiza