Brown adipose tissue (BAT) may play a significant role in energy expenditure in adult humans. We have reported that BAT is highly prevalent in the neck, particularly the supraclavicular (SClv) region of adults (Lee et al. JCEM, 2011;96:2405). Glucocorticoids (GC) play a major role in adipogenesis and energy metabolism, however, the role of GCs on human BAT has not been determined. We aimed to assess the role of GC on BAT expansion and differentiation.
We have established primary culture of brown adipocytes (BA) isolated from biopsies of SClv BAT, and from white adipocytes (WA) from subcutaneous white adipose tissue (WAT) as control (Lee et al. Endocrinology 2011;152:3597). Following the proliferation of preadipocytes to confluence, they are differentiated over the course of 9 days into mature adipocytes. Preadipocytes were grown in the presence of dexamethasone (0, 1.0 or 10µM) during 7 days of proliferation, and cell growth was quantified a non-radioactive cell proliferation assay. Confluent preadipocytes were differentiated for 9 days in the presence of dexamethasone (0, 0.1, 1.0 or 10µM) and gene expression determined using by qPCR.
GC treatment significantly stimulates the proliferation of SClv BA (∆max +30 ± 3%, p<0.05), whilst inhibiting subcutaneous WA (∆max -10 ± 3%, p<0.01), in a dose dependent manner. BA differentiation is characterised by increased expression of Ucp1 (peak of 500-fold), Adrß3 (peak of 20-fold), Dio2 (peak of 50-fold), Cidea (peak of 250-fold) and Pgc1a (peak of 4.5-fold). GC treatment during differentiation further enhanced the expression of several BAT markers, including Ucp1, Cidea and Pgc1a with the strongest effects seen at 10µM dexamethasone.
These results suggest that GC treatment promotes the expansion of BA stem cells whilst inhibiting WA stem cell proliferation, and enhances the expression of classical BAT genes during the differentiation process.
This work is supported by the NHMRC of Australia