Twist-1 Expression in Human Fat Depots and Changes with Diabetes and Bariatric Surgery

Twist-1 Expression in Human Fat Depots and Changes with Diabetes and Bariatric Surgery Twist-1 is a transcription fac Twist-1 is a transcription factor highly expressed by both adipocytes and immune cells in white adipose tissue (AT) in humans. Low twist-1 is correlated with insulin resistance and obesity. However the expression and role of twist-1 in different cell types and AT depots in obesity and type 2 diabetes (T2DM) is not known. The aim of this study was to determine the expression pattern for twist-1 in subcutaneous (SC) and omental (OM) AT in humans with obesity and T2DM and following bariatric surgery. The correlation between twist-1 and inflammatory markers expression in AT was also examined. Paired biopsies of SC and OM adipose tissues were collected from 16 obese subjects (8 T2DM, 8 controls). Also, paired biopsies were collected from 8 T2DM subjects at the time of bariatric surgery and again after a median of 12.5 months. Twist-1 expression was examined in total adipose tissue, adipocytes and stromal vascular fraction (SVF) by real-time PCR. Protein was determined by immunohistochemistry. Inflammatory cytokines and lipoxygenases (ALOX) were also measured by real-time PCR. In all subjects, twist-1 mRNA in SC was 3.5-, 7.5- and, 24.2-fold higher than in OM in AT, adipocytes and SVF, respectively(p[lt]0.01, by both paired and unpaired Student[apos]s t test). In T2DM subjects OM and SC expression of twist-1 was 2-4-fold lower (p[lt]0.05). These results were paralleled by similar differences in protein expression. In SC of T2DM compared to controls, twist-1 was 4-fold lower in SVF (p[lt]0.01) and not changed in adipocytes while in OM expression was 16-fold lower in adipocytes (p[lt]0.001) and similar in SVF. Interestingly, twist-1 expression was significantly increased in OM but not SC AT in T2DM subjects following bariatric surgery. Twist-1 expression was significantly and negatively correlated with expression of inflammatory genes IL-12a, IL-6 and all ALOX 12,15a and 15b in all of the subjects. Also, in 24 h cultured human AT explants twist-1 expression was 2.2-fold lower (p[lt]0.05) after treatment with 10-50[mu]M IL-12. These new results suggest that twist-1 is a negative modulator and marker of inflammation in both the adipocyte and immune cell components of AT in human obesity and T2DM. JERRY L. NADLER, QIAN MA, JOSHUA J. BROTMAN, ANCA D. DOBRIAN 1583-P Norfolk, VA Integrated Physiology - Adipocyte Biology