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- Title:
COL6A3 expression in adipocytes associates with insulin resistance and depends on PPAR? and adipocyte size.
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- 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
- Abstract:
- COL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration.COL6A3 mRNA in abdominal subcutaneous adipose samples was compared between (1) BMI-matched obese subjects resistant or sensitive to insulin (surgical whole tissue biopsies, n = 30/group), (2) lean/overweight and obese subjects (isolated adipocytes from collagenase-treated surgical biopsies, n = 11/group), (3) developing primary human adipocytes with/without knockdown of the insulin-sensitizing adipogenic gene PPARG (collagenase-treated lipoaspirate, n = 5), and (4) small and large adipocytes from lean/overweight subjects (collagenase-treated surgical biopsies or lipoaspirate, n = 10). Insulin resistance and sensitivity were assessed by euglycemic-hyperinsulinemic clamp (glucose infusion rate <60 and >70 ?mol kg(-1) min(-1) , respectively) (1), or by HOMA-IR and TG/HDL ratio (2).Whole tissue COL6A3 mRNA was 2.6-fold higher in insulin resistant compared to sensitive subjects (P < 0.001). In isolated adipocytes, COL6A3 mRNA correlated positively with BMI (P = 0.007), HOMA-IR (P = 0.039), and TG/HDL (P = 0.004). PPARG knockdown in developing adipocytes increased COL6A3 mRNA 1.5-fold (P = 0.043). The inverse relationship with adipocyte development was further supported by 2.8-fold higher COL6A3 mRNA in small compared to large adipocytes (P = 0.004).Increased adipocyte COL6A3 expression associates with insulin resistance in humans, which may involve impaired PPAR?-mediated adipocyte development.
- Journal title abbreviation:
- Obesity (Silver Spring)
- Year:
- 2014
- Journal volume:
- 22
- Journal issue:
- 8
- Pages contribution:
- 1807-13
- Language:
- eng
- Fulltext / DOI:
- doi:10.1002/oby.20758
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/24719315
- Print-ISSN:
- 1930-7381
- TUM Institution:
- Else Kröner-Fresenius-Zentrum für Ernährungsmedizin - Klinik für Ernährungsmedizin
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