TY - JOUR
T1 - Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome
AU - Jialal, Ishwarlal
AU - Devaraj, Sridevi
AU - Bettaieb, Ahmed
AU - Haj, Fawaz
AU - Adams-Huet, Beverley
N1 - Publisher Copyright:
© 2015.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
KW - Adipose tissue
KW - Fetuin A
KW - Lipopolysaccharide binding protein
KW - Metabolic syndrome
KW - TLR
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U2 - 10.1016/j.atherosclerosis.2015.04.814
DO - 10.1016/j.atherosclerosis.2015.04.814
M3 - Article
C2 - 25978344
AN - SCOPUS:84929155377
SN - 0021-9150
VL - 241
SP - 130
EP - 137
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -