دورية أكاديمية
أعرض في EDS

Systems genetics analysis of human body fat distribution genes identifies adipocyte processes.

التفاصيل البيبلوغرافية
العنوان: Systems genetics analysis of human body fat distribution genes identifies adipocyte processes.
المؤلفون: Reed JN; https://ror.org/0153tk833 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.; https://ror.org/0153tk833 Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Huang J; Novo Nordisk Research Center China, Novo Nordisk A/S, Beijing, China., Li Y; Novo Nordisk Research Center China, Novo Nordisk A/S, Beijing, China., Ma L; https://ror.org/04a9tmd77 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Banka D; https://ror.org/0153tk833 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA., Wabitsch M; Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, Ulm University Medical Centre, Ulm, Germany., Wang T; Novo Nordisk Research Center China, Novo Nordisk A/S, Beijing, China., Ding W; Novo Nordisk Research Center China, Novo Nordisk A/S, Beijing, China., Björkegren JL; https://ror.org/04a9tmd77 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden., Civelek M; https://ror.org/0153tk833 Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA mete@virginia.edu.; https://ror.org/0153tk833 Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
المصدر: Life science alliance [Life Sci Alliance] 2024 May 03; Vol. 7 (7). Date of Electronic Publication: 2024 May 03 (Print Publication: 2024).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]-
مواضيع طبية MeSH: Adipocytes*/metabolism , Body Fat Distribution* , Adipogenesis*/genetics, Humans ; Male ; Female ; Body Mass Index ; Adult ; Gene Regulatory Networks ; Middle Aged ; Bayes Theorem ; Waist-Hip Ratio ; Adipose Tissue/metabolism ; Wnt Signaling Pathway/genetics ; Gene Expression Regulation/genetics ; Systems Biology/methods
مستخلص: Excess abdominal fat is a sexually dimorphic risk factor for cardio-metabolic disease and is approximated by the waist-to-hip ratio adjusted for body mass index (WHR adjBMI ). Whereas this trait is highly heritable, few causal genes are known. We aimed to identify novel drivers of WHR adjBMI using systems genetics. We used two independent cohorts of adipose tissue gene expression and constructed sex- and depot-specific Bayesian networks to model gene-gene interactions from 8,492 genes. Using key driver analysis, we identified genes that, in silico and putatively in vitro, regulate many others. 51-119 key drivers in each network were replicated in both cohorts. In other cell types, 23 of these genes are found in crucial adipocyte pathways: Wnt signaling or mitochondrial function. We overexpressed or down-regulated seven key driver genes in human subcutaneous pre-adipocytes. Key driver genes ANAPC2 and RSPO1 inhibited adipogenesis, whereas PSME3 increased adipogenesis. RSPO1 increased Wnt signaling activity. In differentiated adipocytes, MIGA1 and UBR1 down-regulation led to mitochondrial dysfunction. These five genes regulate adipocyte function, and we hypothesize that they regulate fat distribution.
(© 2024 Reed et al.)
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تواريخ الأحداث: Date Created: 20240503 Date Completed: 20240503 Latest Revision: 20240513
رمز التحديث: 20240513
مُعرف محوري في PubMed: PMC11068934
DOI: 10.26508/lsa.202402603
PMID: 38702075
قاعدة البيانات: MEDLINE
الوصف
تدمد:2575-1077
DOI:10.26508/lsa.202402603