Fetuin-A levels are increased in the adipose tissue of diabetic obese humans but not in circulation

• Published in: Lipids in health and disease Vol. 17; no. 1; p. 291
• Main Authors: Khadir, Abdelkrim, Kavalakatt, Sina, Madhu, Dhanya, Hammad, Maha, Devarajan, Sriraman, Tuomilehto, Jaakko, Tiss, Ali
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22-12-2018; BioMed Central; BMC
• Subjects: Adipose tissue; Body fat; Cell culture; Cell lines; Confocal microscopy; Culture media; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Enzyme-linked immunosorbent assay; Exercise; Fetuin-A; Gene expression; Genetic aspects; Immunoblotting; Insulin resistance; Leukocytes (mononuclear); mRNA; Obesity; Peptide hormones; Peripheral blood mononuclear cells; Phenotypes; Physical exercise; Physiological aspects; Studies; Kuwait; Physical exercise; Obesity; Insulin resistance; Fetuin-A; Adipose tissue
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-018-0919-x

The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. In this study, we aimed to assess the circulating levels of fetuin-A and its expression in subcutaneous adipose tissue (SAT) from diabetic and non-diabetic obese subjects and their modulation by exercise.
SAT and blood were obtained from adults obese (diabetic, n=118 and non-diabetic, n=166) before and after a 3-month exercise program (diabetic, n=40 and non-diabetic, n=36, respectively). Plasma fetuin-A was assayed using ELISA. The presence and expression of fetuin-A in SAT, peripheral blood mononuclear cells (PBMCs) and cell lines (3T3-L1, THP-1, HepG2, RAW 264.7) were analysed using confocal microscopy, immunoblotting and qRT-PCR.
Plasma fetuin-A level did not significantly differ between diabetic and non-diabetic obese subjects. However, when the non-diabetic group was divided into metabolically healthy and unhealthy phenotypes, significantly higher fetuin-A level was observed in the unhealthy sub-group. Circulating fetuin-A was mainly associated with glycaemic markers. In SAT, fetuin-A protein level was significantly higher in the diabetic obese subjects but its mRNA was not detected. Similarly, fetuin-A protein was detected in PBMCs, but its mRNA was not. In line with this, the use of various cell lines and culture media indicated that the presence of fetuin-A in SAT and PBMCs was due to its uptake from circulation rather than its endogenous expression. Finally, physical exercise decreased fetuin-A levels in both plasma and SAT in both groups.
Fetuin-A levels increased in association with diabetes in SAT but not in circulation in the obese subjects. Moreover, physical exercise decreased fetuin-A level. Fetuin-A potentially acts as a hepatokine taken up by other tissues, such as adipose tissue.