Acute Antilipolytic Effects of Elevated Levels of Corticosterone in Differentiated Murine White Adipocytes

Glucocorticoids (GC) are a group of steroid hormones that affect white adipose tissue (WAT) lipogenesis (biosynthesis of triglycerides) and lipolysis (hydrolysis of triglycerides). At the cellular level, prolonged GC exposure promotes increases in WAT lipolysis through glucocorticoid receptor (GR) mediated mechanisms; however, elevated GC levels can decrease WAT lipolysis through unknown mechanisms that remain unclear. Evidence suggests that GCs may also have actions independent of GR binding, though how these GR-independent effects impact WAT lipolysis also remains unknown. Therefore, the objective of this study was to assess how elevated GCs impact WAT lipolysis through non-GR-mediated mechanisms. Mature white adipocytes (3T3-L1 cells) were acutely exposed to various GC concentrations (10-200 µM), and lipolytic rates were quantified in the presence or absence of lipolytic pathway inhibitors or siRNA GR. Contradictory to chronic in vitro and in vivo studies, acute (1-4 h), high GC levels (50-200 µM) significantly decreased basal lipolysis. These inhibitory effects persisted when the GR or gene transcription was blocked after 1 h, suggesting GCs inhibition of lipolysis occurred independent of GR-mediated pathways. Interestingly, 1 h of elevated GC exposure decreased hormone sensitive lipase (HSL) activity through a reduction of ser563 phosphorylation. However, this decrease in HSL activity was independent of cAMP signalling, as elevated GCs had no effect on cAMP or PKA activity relative to controls. Ex vivo adipose explant studies also revealed depot-specific suppression of lipolysis by corticosterone. Therefore, elevated GC levels can acutely decrease lipolysis in WAT independent of GR-mediated mechanisms, suggesting an alternative pathway in which GCs act to regulate lipolysis.<b>NEW & NOTEWORTHY</b> This research led to novel findings about acute, non-GR-mediated effects of elevated CORT on lipolysis in WAT. Most work has been done on lower GC levels and chronic durations, and does not fully capture the acute, non-GR-mediated effects of GCs in WAT. These acute, non-GR-mediated effects have been studied in tissues such as smooth muscle and bronchial epithelial cells, but to our knowledge, no study reported on such effects in WAT.