Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes
MJ Lee, SK Fried - American Journal of Physiology …, 2012 - journals.physiology.org
MJ Lee, SK Fried
American Journal of Physiology-Endocrinology and Metabolism, 2012•journals.physiology.orgHigh concentrations of TNF within obese adipose tissue increase basal lipolysis and
antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of
glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the
hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs
antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of
lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX) …
antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of
glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the
hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs
antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of
lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX) …
High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX), or DEX + TNF for up to 48 h. TNF not only increased basal lipolysis, it caused resistance to the antilipolytic effects of insulin in human adipocytes. DEX alone did not significantly affect lipolysis. Cotreatment with DEX blocked TNF induction of basal lipolysis and insulin resistance by antagonizing TNF stimulation of PKA-mediated phosphorylation of hormone-sensitive lipase (HSL) at Ser563 and Ser660 and perilipin. TNF did not affect perilipin, HSL, or phosphodiesterase-3B mass but paradoxically suppressed adipose tissue triglyceride lipase expression, and this effect was blocked by DEX. The extent to which GCs can restrain the lipolytic actions of TNF may both diminish the potentially deleterious effects of excess lipolysis and contribute to fat accumulation in obesity.
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