Title |
COL6A3 is regulated by leptin in human adipose tissue and reduced in obesity.
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Published in |
Molecular Endocrinology, January 2015
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DOI | 10.1210/en.2014-1042 |
Pubmed ID | |
Authors |
Laura J McCulloch, Tom J Rawling, Kajsa Sjöholm, Niclas Franck, Simon N Dankel, Emily J Price, Bridget Knight, Neil H Liversedge, Gunnar Mellgren, Fredrik Nystrom, Lena M Carlsson, Katarina Kos |
Abstract |
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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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 2% |
Unknown | 65 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 14 | 21% |
Researcher | 7 | 11% |
Student > Doctoral Student | 6 | 9% |
Student > Bachelor | 6 | 9% |
Professor | 4 | 6% |
Other | 13 | 20% |
Unknown | 16 | 24% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 20 | 30% |
Medicine and Dentistry | 12 | 18% |
Biochemistry, Genetics and Molecular Biology | 10 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
Social Sciences | 2 | 3% |
Other | 3 | 5% |
Unknown | 17 | 26% |