Abstract
BackgroundThe 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.MethodsSAT 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.ResultsPlasma 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.ConclusionsFetuin-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.
Highlights
The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear
These conflicting results might be related to the different localizations of atherosclerosis and the pleiotropic effects of fetuin-A that are reflected by its dual function as inhibitor of vascular ectopic calcification [21] and its association with insulin resistance, T2D, metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) [6, 22, 23]
Plasma fetuin-A levels are not affected by diabetes in obese but modulated by physical exercise In this study, 166 non-diabetic (67 males and 99 females) and 118 diabetic (64 males and 54 females) subjects were enrolled
Summary
The hepatokine fetuin-A is linked to obesity and type 2 diabetes, but its presence and expression in adipose tissue remain unclear. 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 Metabolic diseases such as obesity and diabetes are characterised by insulin resistance in peripheral tissues [1]. In a prospective study with multi-ethnic population, no overall association between serum fetuin-A and CVD events was found but fetuin-A was associated with CVD risk in subjects with impaired fasting glucose or diabetes [20] These conflicting results might be related to the different localizations of atherosclerosis and the pleiotropic effects of fetuin-A that are reflected by its dual function as inhibitor of vascular ectopic calcification [21] and its association with insulin resistance, T2D, metabolic syndrome and NAFLD [6, 22, 23]
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