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


CONCLUSIONS
Increased adipocyte COL6A3 expression associates with insulin resistance in humans, which may involve impaired PPARγ-mediated adipocyte development.
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.
Simon N
SN
Dankel
Jessica
J
Svärd
Simone
S
Matthä
Melina
M
Claussnitzer
Nora
N
Klöting
Viktoria
V
Glunk
Zinayida
Z
Fandalyuk
Elise
E
Grytten
Margit H
MH
Solsvik
Hans-Jørgen
HJ
Nielsen
Christian
C
Busch
Hans
H
Hauner
Matthias
M
Blüher
Thomas
T
Skurk
Jørn V
JV
Sagen
Gunnar
G
Mellgren
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D002478:Cells, Cultured; D024142:Collagen Type VI / Q000235:genetics; D055785:Gene Knockdown Techniques; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D050177:Overweight / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D024142:Collagen Type VI; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger