COL6A3 expression in adipocytes associates with insulin resistance and depends on PPARγ and adipocyte size. (10th April 2014)

• Record Type: Journal Article
• Authors: Dankel, Simon N.; Svärd, Jessica; Matthä, Simone; Claussnitzer, Melina; Klöting, Nora; Glunk, Viktoria; Fandalyuk, Zinayida; Grytten, Elise; Solsvik, Margit H.; Nielsen, Hans‐Jørgen; Busch, Christian; Hauner, Hans; Blüher, Matthias; Skurk, Thomas; Sagen, Jørn V.; Mellgren, Gunnar
• Is Part Of: Obesity. Volume 22:Number 8(2014:Aug.)
• Page Start: 1807
• Page End: 1813
• Publication Date: 2014-04-10
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20758
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20758-sec-0001" sec-type="section"> <title>Objective</title> <p> <italic>COL6A3</italic> may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking <italic>COL6A3</italic> with insulin resistance warrants exploration.</p> </sec> <sec id="oby20758-sec-0002" sec-type="section"> <title>Methods</title> <p> <italic>COL6A3</italic> mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI‐matched obese subjects resistant or sensitive to insulin (surgical whole tissue biopsies, <italic>n</italic> = 30/group), (2) lean/overweight and obese subjects (isolated adipocytes from collagenase‐treated surgical biopsies, <italic>n</italic> = 11/group), (3) developing primary human adipocytes with/without knockdown of the insulin‐sensitizing adipogenic gene <italic>PPARG</italic> (collagenase‐treated lipoaspirate, <italic>n</italic> = 5), and (4) small and large adipocytes from lean/overweight subjects (collagenase‐treated surgical biopsies or lipoaspirate, <italic>n</italic> = 10). Insulin resistance and sensitivity were assessed by euglycemic‐hyperinsulinemic clamp (glucose infusion rate <60 and >70 μmol kg<sup>−1</sup> min<sup>−1</sup>, respectively) (1), or by HOMA‐IR and TG/HDL ratio (2).</p> </sec> <sec id="oby20758-sec-0003" sec-type="section"> <title>Results</title> <p>Whole tissue <italic>COL6A3</italic> mRNA was 2.6‐fold higher in insulin resistant compared to sensitive subjects (<italic>P</italic> < 0.001). In isolated adipocytes, <italic>COL6A3</italic> mRNA correlated positively with BMI (<italic>P</italic> = 0.007), HOMA‐IR (<italic>P</italic> = 0.039), and TG/HDL (<italic>P</italic> = 0.004). <italic>PPARG</italic> knockdown in developing adipocytes increased <italic>COL6A3</italic> mRNA 1.5‐fold (<italic>P</italic> = 0.043). The inverse relationship with adipocyte development was further supported by 2.8‐fold higher <italic>COL6A3</italic> mRNA in small compared to large adipocytes (<italic>P</italic> = 0.004).</p> </sec> <sec id="oby20758-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Increased adipocyte <italic>COL6A3</italic> expression associates with insulin resistance in humans, which may involve impaired PPARγ‐mediated adipocyte development.</p> </sec> </abstract>