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Atherosclerosis. 2015 Jul;241(1):130-7. doi: 10.1016/j.atherosclerosis.2015.04.814. Epub 2015 May 1.

Increased adipose tissue secretion of Fetuin-A, lipopolysaccharide-binding protein and high-mobility group box protein 1 in metabolic syndrome.

Author information

1
Laboratory for Atherosclerosis and Metabolic Research, Department of Pathology, Division of Endocrinology, Diabetes and Metabolism, University of California Davis Medical Center, Sacramento, CA, USA; Medical Services, VA Medical Center, Mather, CA, USA. Electronic address: ishwarlal.jialal@ucdmc.ucdavis.edu.
2
Department of Pathology & Immunology, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA.
3
Department of Nutrition, University of California Davis, Davis, CA, USA.
4
Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

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:

Adipose tissue; Fetuin A; Lipopolysaccharide binding protein; Metabolic syndrome; TLR

[Indexed for MEDLINE]

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