Highlights
- •Increased secretion of Fetuin A and LBP from adipose tissue of MetS subjects, which correlates with insulin resistance.
- •The study documents increased secretion of DAMP, HMGB1 and increased TLR2 and TLR4 protein in subcutaneous adipose.
- •We demonstrate increased mRNA for Fetuin A, LBP and HMGB1 in mice fat depots and adipocytes.
Abstract
Objective
Adipose Tissue (AT) dysregulation contributes to the pro-inflammatory state and insulin
resistance of Metabolic Syndrome (MetS). We examined AT secretion of the hepatokine,
Fetuin-A, LBP, sCD14 and HMGB-1, and toll-like receptor 2 and 4 protein levels in
MetS and controls.
Design and methods
Secreted levels of Fetuin-A, LBP, HMGB-1 and sCD14 and TLR2 and TLR4 protein in AT
of controls and MetS patients were assayed. Also mRNA and protein for Fetuin-A, LBP,
sCD14 and HMGB-1 were studied in subcutaneous fat depot of mice and during adipocyte
differentiation.
Results
Secretion of Fetuin-A, LBP and HMGB-1 from AT were significantly increased in MetS
(n = 28) compared to controls (n = 25), even after adjustment for adiposity. There
were no significant differences in sCD14. Both LBP and Fetuin-A correlated significantly
with HOMA-IR and increased significantly with increasing features of MetS. There was
a significant increase in AT TLR2 and TLR4 protein in MetS compared to controls. Expression
of Fetuin-A and LBP were significantly higher in subcutaneous white adipose tissue of HFD fed mice as
well as in ob/ob mice compared to C57BL6/J control mice (n = 6 per group). Additionally
mRNA and protein levels of FetA, LBP and HMGB-1 increased during differentiation of 3T3-L1 adipocytes.
Conclusions
We make the novel observation of increased secretion of Fetuin A, LBP and HMGB-1 from
AT and hypothesize that these engage TLRs in AT and other tissues contributing to
the pro-inflammatory state and insulin resistance of MetS.
Keywords
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Article Info
Publication History
Published online: April 30, 2015
Accepted:
April 24,
2015
Received in revised form:
April 24,
2015
Received:
February 20,
2015
Identification
Copyright
Published by Elsevier Inc.
