COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity

2.50
Hdl Handle:
http://hdl.handle.net/11287/593941
Title:
COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity
Authors:
McCulloch, Laura J.; Rawling, T. J.; Sjoholm, K.; Franck, N.; Dankel, S. N.; Price, E. J.; Knight, Bridget; Liversedge, Neil H.; Mellgren, G.; Nystrom, F.; Carlsson, L. M.; Kos, K.
Abstract:
Fibrosis of adipose tissue (AT) increases AT rigidity, reduces its expandability, and contributes to metabolic dysfunction. Collagen type VI, alpha3 (COL6A3) encodes 1 subunit of a fibrotic extracellular matrix protein highly expressed in rodent AT. Knockout 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. Characterization of COL6A3 in human AT showed 5-fold higher expression in the stromalvascular fraction compared with adipocyte expression and significantly higher expression in subcutaneous AT (SCAT) than omental AT. In both depots, COL6A3 expression appeared to be lowered in obesity, whereas diet- and surgery-induced weight loss increased COL6A3 expression in SCAT. 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, because 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 signaling pathway in human AT and suggests an additional mechanism by which leptin can regulate extracellular matrix composition and, with it, AT expandability.
Citation:
Endocrinology. 2015 Jan;156(1):134-46.
Publisher:
Endocrine Society
Journal:
Endocrinology
Issue Date:
1-Jan-2015
URI:
http://hdl.handle.net/11287/593941
DOI:
10.1210/en.2014-1042
PubMed ID:
25337653
Additional Links:
http://press.endocrine.org/doi/10.1210/en.2014-1042?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmed
Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
eng
ISSN:
1945-7170
Appears in Collections:
2015 RD&E publications; Obstetrics, Gynaecology & Maternity Services; Honorary contracts publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMcCulloch, Laura J.en
dc.contributor.authorRawling, T. J.en
dc.contributor.authorSjoholm, K.en
dc.contributor.authorFranck, N.en
dc.contributor.authorDankel, S. N.en
dc.contributor.authorPrice, E. J.en
dc.contributor.authorKnight, Bridgeten
dc.contributor.authorLiversedge, Neil H.en
dc.contributor.authorMellgren, G.en
dc.contributor.authorNystrom, F.en
dc.contributor.authorCarlsson, L. M.en
dc.contributor.authorKos, K.en
dc.date.accessioned2016-01-19T12:37:40Zen
dc.date.available2016-01-19T12:37:40Zen
dc.date.issued2015-01-01en
dc.identifier.citationEndocrinology. 2015 Jan;156(1):134-46.en
dc.identifier.issn1945-7170en
dc.identifier.pmid25337653en
dc.identifier.doi10.1210/en.2014-1042en
dc.identifier.urihttp://hdl.handle.net/11287/593941en
dc.description.abstractFibrosis of adipose tissue (AT) increases AT rigidity, reduces its expandability, and contributes to metabolic dysfunction. Collagen type VI, alpha3 (COL6A3) encodes 1 subunit of a fibrotic extracellular matrix protein highly expressed in rodent AT. Knockout 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. Characterization of COL6A3 in human AT showed 5-fold higher expression in the stromalvascular fraction compared with adipocyte expression and significantly higher expression in subcutaneous AT (SCAT) than omental AT. In both depots, COL6A3 expression appeared to be lowered in obesity, whereas diet- and surgery-induced weight loss increased COL6A3 expression in SCAT. 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, because 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 signaling pathway in human AT and suggests an additional mechanism by which leptin can regulate extracellular matrix composition and, with it, AT expandability.en
dc.language.isoengen
dc.publisherEndocrine Societyen
dc.relation.urlhttp://press.endocrine.org/doi/10.1210/en.2014-1042?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%3dpubmeden
dc.titleCOL6A3 is regulated by leptin in human adipose tissue and reduced in obesityen
dc.typeJournal Articleen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.identifier.journalEndocrinologyen

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