Thyroid hormone responsive Spot 14 increases during differentiation of human adipocytes and its expression is down-regulated in obese subjects

Context: Very limited information is available regarding the function of human thyroid hormone responsive Spot 14 (human S14, hS14) in adipogenesis and human adiposity. Objective: To evaluate hS14 levels during differentiation of human pre-adipocytes, in human fat depots and isolated fat cells. Design: This was a cross-sectional study. Subjects: A total of 161 omental (OM) and 87 subcutaneous (SC) adipose tissue samples obtained during elective surgical procedures from a population who varied widely in terms of obesity. Measurements: hS14 gene expression and protein levels during adipogenesis were assessed by RT-PCR, western blot, and using an automated confocal imaging approach. Results: hS14 gene expression levels were decreased in OM adipose tissue from overweight ( 42.0%) and obese subjects (-56.5%) compared with lean subjects (P<0.05 and P<0.0001, respectively). hS14 mRNA (but not hS14-related) was inversely associated with obesity measures such as body mass index (P = 0.001), percent fat mass (P = 0.001), waist-to-hip ratio (P = 0.020), and systolic blood pressure (P = 0.031). hS14 gene expression and protein levels were up-regulated at the early stages of differentiation of human pre-adipocytes as well as for 3T3-L1 cells. That observation was most prominent in those individual cells exhibiting the more marked differentiation features. hS14 gene expression levels increased by similar to 45000-fold in mature adipocytes. Increased hS14 levels were also found in stromal-vascular cells/pre-adipocytes (3.8-fold, P<0.05) and in adipose tissue samples (1.9-fold, P<0.0001) from SC compared with OM fat depots. Conclusions: These results suggest that hS14 is involved in human adipogenesis, but inversely related to obesity and OM fat accumulation. International Journal of Obesity (2010) 34, 487-499; doi: 10.1038/ijo.2009.263; published online 22 December 2009