Adipogenic and lipolytic effects of chronic glucocorticoid exposure

Abstract

Glucocorticoids have been proposed to be both adipogenic and lipolytic in action within adipose tissue, although it is unknown whether these actions can occur simultaneously. Here we investigate both the in vitro and in vivo effects of corticosterone (Cort) on adipose tissue metabolism. Cort increased 3T3-L1 preadipocyte differentiation in a concentration-dependent manner, but did not increase lipogenesis in adipocytes. Cort increased lipolysis within adipocytes in a concentration-dependent manner (maximum effect at 1-10 μM). Surprisingly, removal of Cort further increased lipolytic rates (∼320% above control, P < 0.05), indicating a residual effect on basal lipolysis. mRNA and protein expression of adipose triglyceride lipase and phosphorylated status of hormone sensitive lipase (Ser563/Ser660) were increased with 48 h of Cort treatment. To test these responses in vivo, Sprague-Dawley rats were subcutaneously implanted with wax pellets with/without Cort (300 mg). After 10 days, adipose depots were removed and cultured ex vivo. Both free fatty acids and glycerol concentrations were elevated in fed and fasting conditions in Cort-treated rats. Despite increased lipolysis, Cort rats had more visceral adiposity than sham rats (10.2 vs. 6.9 g/kg body wt, P < 0.05). Visceral adipocytes from Cort rats were smaller and more numerous than those in sham rats, suggesting that adipogenesis occurred through preadipocyte differentiation rather than adipocyte hypertrophy. Visceral, but not subcutaneous, adipocyte cultures from Cort-treated rats displayed a 1.5-fold increase in basal lipolytic rates compared with sham rats (P < 0.05). Taken together, our findings demonstrate that chronic glucocorticoid exposure stimulates both lipolysis and adipogenesis in visceral adipose tissue but favors adipogenesis primarily through preadipocyte differentiation.

Angiopoietin-like 4 (Angptl4) Protein Is a Physiological Mediator of Intracellular Lipolysis in Murine Adipocytes

“…Glucocorticoid levels fluctuate throughout the day in accordance with this, displaying their largest peak in the morning following an overnight fast (12). Although the involvement of glucocorticoid action in fasting-induced WAT lipolysis has been described (13,14), the extent to which glucocorticoids regulate intracellular adipocyte lipolysis and the mechanisms by which this occurs remain to be determined.…”

Depot- and sex-specific effects of maternal obesity in offspring’s adipose tissue

“…Several lines of evidence prompted us to explore whether sensitivity of WAT to glucocorticoid (GC) was modified in offspring. First, GC alone or in interaction with insulin regulates the differentiation of preadipocytes and lipogenic genes (Campbell et al 2011). Second, a close link between chronic excess of plasma GC levels and/or increased GC sensitivity within WAT (i.e.…”

The effects of high fat diet on the basal activity of the hypothalamus–pituitary–adrenal axis in mice

“…The HFD increases lipoprotein lipase activity (Petit et al 2007), which would direct circulating triglycerides toward peripheral adipose tissues for storage. Corticosterone impairs glucose tolerance (Karatsoreos et al 2010) and is a lipolytic hormone (Campbell et al 2011). Therefore downregulation of 11b-HSD-1 expression would protect the adipose tissue from further insulin resistance.…”