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Pregled bibliografske jedinice broj: 1260068

Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance

Lotta, Luca A; EPIC-InterAct Consortium; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J et al.
Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance // Nature Genetics, 49 (2016), 1; 17-26 doi:10.1038/ng.3714 (međunarodna recenzija, članak, znanstveni)

CROSBI ID: 1260068 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance

Autori
Lotta, Luca A ; EPIC-InterAct Consortium ; Gulati, Pawan ; Day, Felix R ; Payne, Felicity ; Ongen, Halit ; van de Bunt, Martijn ; Gaulton, Kyle J ; Eicher, John D ; Sharp, Stephen J ; Luan, Jian'an ; De Lucia Rolfe, Emanuella ; Stewart, Isobel D ; Wheeler, Eleanor ; Willems, Sara M ; Adams, Claire ; Yaghootkar, Hanieh ; Forouhi, Nita G ; Khaw, Kay-Tee ; Johnson, Andrew D ; Semple, Robert K ; Frayling, Timothy ; Perry, John R B ; Dermitzakis, Emmanouil ; McCarthy, Mark I ; Barroso, Inês ; Wareham, Nicholas J ; Savage, David B ; Langenberg, Claudia ; O'Rahilly, Stephen ; Scott, Robert A ; Cambridge FPLD1 Consortium

Izvornik
Nature Genetics (1061-4036) 49 (2016), 1; 17-26

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Integrative genomic analysis, peripheral adipose storage capacity, human insulin resistance

Sažetak
Insulin resistance is a key mediator of obesity- related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

Izvorni jezik
Engleski



POVEZANOST RADA

Ustanove:
Medicinski fakultet, Zagreb

Profili:

Avatar Url Lea Smirčić-Duvnjak (autor)

Poveznice na cjeloviti tekst rada:

doi

Citiraj ovu publikaciju:

Lotta, Luca A; EPIC-InterAct Consortium; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J et al.
Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance // Nature Genetics, 49 (2016), 1; 17-26 doi:10.1038/ng.3714 (međunarodna recenzija, članak, znanstveni)
Lotta, L., EPIC-InterAct Consortium, Gulati, P., Day, F., Payne, F., Ongen, H., van de Bunt, M., Gaulton, K., Eicher, J. & Sharp, S. (2016) Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance. Nature Genetics, 49 (1), 17-26 doi:10.1038/ng.3714.
@article{article, author = {Lotta, Luca A and Gulati, Pawan and Day, Felix R and Payne, Felicity and Ongen, Halit and van de Bunt, Martijn and Gaulton, Kyle J and Eicher, John D and Sharp, Stephen J and Luan, Jian'an and De Lucia Rolfe, Emanuella and Stewart, Isobel D and Wheeler, Eleanor and Willems, Sara M and Adams, Claire and Yaghootkar, Hanieh and Forouhi, Nita G and Khaw, Kay-Tee and Johnson, Andrew D and Semple, Robert K and Frayling, Timothy and Perry, John R B and Dermitzakis, Emmanouil and McCarthy, Mark I and Barroso, In\^{e}s and Wareham, Nicholas J and Savage, David B and Langenberg, Claudia and O'Rahilly, Stephen and Scott, Robert A}, year = {2016}, pages = {17-26}, DOI = {10.1038/ng.3714}, keywords = {Integrative genomic analysis, peripheral adipose storage capacity, human insulin resistance}, journal = {Nature Genetics}, doi = {10.1038/ng.3714}, volume = {49}, number = {1}, issn = {1061-4036}, title = {Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance}, keyword = {Integrative genomic analysis, peripheral adipose storage capacity, human insulin resistance} }
@article{article, author = {Lotta, Luca A and Gulati, Pawan and Day, Felix R and Payne, Felicity and Ongen, Halit and van de Bunt, Martijn and Gaulton, Kyle J and Eicher, John D and Sharp, Stephen J and Luan, Jian'an and De Lucia Rolfe, Emanuella and Stewart, Isobel D and Wheeler, Eleanor and Willems, Sara M and Adams, Claire and Yaghootkar, Hanieh and Forouhi, Nita G and Khaw, Kay-Tee and Johnson, Andrew D and Semple, Robert K and Frayling, Timothy and Perry, John R B and Dermitzakis, Emmanouil and McCarthy, Mark I and Barroso, In\^{e}s and Wareham, Nicholas J and Savage, David B and Langenberg, Claudia and O'Rahilly, Stephen and Scott, Robert A}, year = {2016}, pages = {17-26}, DOI = {10.1038/ng.3714}, keywords = {Integrative genomic analysis, peripheral adipose storage capacity, human insulin resistance}, journal = {Nature Genetics}, doi = {10.1038/ng.3714}, volume = {49}, number = {1}, issn = {1061-4036}, title = {Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance}, keyword = {Integrative genomic analysis, peripheral adipose storage capacity, human insulin resistance} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE
  • Nature Index

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