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Obesity (Silver Spring). 2014 Aug;22(8):1807-13. doi: 10.1002/oby.20758. Epub 2014 Apr 10.

COL6A3 expression in adipocytes associates with insulin resistance and depends on PPARγ and adipocyte size.

Author information

1
Department of Clinical Science, University of Bergen, Bergen, Norway; KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.

Abstract

OBJECTIVE:

COL6A3 may modulate adipose tissue function in obesity and insulin resistance. A role for human adipocytes linking COL6A3 with insulin resistance warrants exploration.

METHODS:

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 μmol kg(-1) min(-1) , respectively) (1), or by HOMA-IR and TG/HDL ratio (2).

RESULTS:

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).

CONCLUSION:

Increased adipocyte COL6A3 expression associates with insulin resistance in humans, which may involve impaired PPARγ-mediated adipocyte development.

PMID:
24719315
DOI:
10.1002/oby.20758
[Indexed for MEDLINE]
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