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COL6A3 is regulated...
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McCulloch, Laura JUniversity of Exeter Medical School, Exeter, UK
(author)
COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity.
- Article/chapterEnglish2015
Publisher, publication year, extent ...
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The Endocrine Society,2015
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LIBRIS-ID:oai:gup.ub.gu.se/206159
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https://gup.ub.gu.se/publication/206159URI
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https://doi.org/10.1210/en.2014-1042DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-112737URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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Fibrosis of adipose tissue (AT) increases AT rigidity, reduces its expandability and contributes to metabolic dysfunction. Collagen type VI, alpha3 (COL6A3) encodes one subunit of a fibrotic extracellular matrix (ECM) protein highly expressed in rodent AT. Knock-out of collagen VI in rodent AT led to a significant improvement in metabolic health in obese, diabetic (ob/ob) mice however, it is unknown whether this collagen has the same metabolic significance in human AT. We therefore aimed to undertake a comprehensive assessment of COL6A3 in relation to human AT and obesity. Characterisation of COL6A3 in human AT showed 5 fold higher expression in the stromalvascular fraction compared with adipocyte expression and significantly higher expression in subcutaneous than omental AT. In both depots COL6A3 expression appeared to be lowered in obesity, whilst diet and surgery-induced weight loss increased COL6A3 expression in subcutaneous AT. Leptin treatment caused a dose dependent decrease in COL6A3 expression although no effect was seen with insulin or glucose treatment and no difference observed in subjects with diabetes. In addition, we found that the collagen expression profile in humans differs significantly from rodents as COL6A3 does not appear to be the predominant collagen in adipose, muscle or liver. Our findings oppose those initially seen in rodent studies and most importantly, demonstrate a direct regulation of COL6A3 by leptin. This highlights the importance of a paracrine leptin signalling pathway in human AT and suggests an additional mechanism by which leptin can regulate ECM composition and with it AT expandability.
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Rawling, Tom JUniversity of Exeter Medical School, Exeter, UK
(author)
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Sjöholm, Kajsa,1971Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,The Sahlgrenska Academy at University of Gothenburg, Sweden(Swepub:gu)xsjohk
(author)
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Franck, NiclasLinköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet(Swepub:liu)nicfr01
(author)
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Nitter, Simon E
(author)
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Price, Emily JUniversity of Exeter Medical School, Exeter, UK
(author)
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Knight, BridgetUniversity of Exeter Medical School, UK
(author)
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Liversedge, Neil HRoyal Devon and Exeter NHS Foundation Trust, UK
(author)
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Mellgren, GunnarUniversity of Bergen and Hormone Laboratory, Haukeland University Hospital, Norway
(author)
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Nyström, FredrikÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för kardiovaskulär medicin,Hälsouniversitetet,Endokrinmedicinska kliniken(Swepub:liu)freny92
(author)
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Carlsson, Lena M S,1957Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,The Sahlgrenska Academy at University of Gothenburg, Sweden(Swepub:gu)xcarle
(author)
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Kos, KatarinaUniversity of Exeter Medical School, Exeter, UK
(author)
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Dankel, Simon NUniversity of Bergen and Hormone Laboratory, Haukeland University Hospital, Norway
(author)
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University of Exeter Medical School, Exeter, UKInstitutionen för medicin, avdelningen för molekylär och klinisk medicin
(creator_code:org_t)
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In:Endocrinology: The Endocrine Society156:1, s. 134-461945-71700013-7227
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McCulloch, Laura ...
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Rawling, Tom J
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Sjöholm, Kajsa, ...
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Franck, Niclas
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Nitter, Simon E
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Price, Emily J
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Knight, Bridget
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Liversedge, Neil ...
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Mellgren, Gunnar
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Nyström, Fredrik
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Kos, Katarina
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Dankel, Simon N
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