Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes

Am J Physiol Endocrinol Metab. 2012 Nov 1;303(9):E1126-33. doi: 10.1152/ajpendo.00228.2012. Epub 2012 Sep 4.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / genetics
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism
  • Dexamethasone / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / pharmacology*
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance*
  • Lipase / genetics
  • Lipase / metabolism
  • Lipolysis / drug effects*
  • Male
  • Middle Aged
  • Perilipin-1
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Sterol Esterase / genetics
  • Sterol Esterase / metabolism
  • Subcutaneous Fat, Abdominal / cytology
  • Subcutaneous Fat, Abdominal / drug effects*
  • Subcutaneous Fat, Abdominal / metabolism
  • Tissue Culture Techniques
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism*


  • Carrier Proteins
  • Glucocorticoids
  • Insulin
  • Perilipin-1
  • Phosphoproteins
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Dexamethasone
  • Cyclic AMP-Dependent Protein Kinases
  • Sterol Esterase
  • Lipase
  • PNPLA2 protein, human
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • PDE3B protein, human