Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase

FEBS Lett. 1994 Oct 10;353(1):33-6. doi: 10.1016/0014-5793(94)01006-4.

Abstract

In vivo, hormone-sensitive lipase (HSL) is known to be phosphorylated on two sites termed the regulatory and basal sites. However, the intracellular role of the basal site or the identity of the protein kinase phosphorylating this site has not been established. We show that 5-amino-4-imidazolecarboxamide ribonucleoside (AICAR) markedly activates cellular AMP-activated protein kinase (AMPK) in a time- and dose-dependent manner. As expected for an agent that activates AMPK intracellularly, AICAR had no effect on the basal activity of HSL. However, preincubation of adipocytes with AICAR led to a reduced response of these cells to the lipolytic agent isoprenaline. AICAR was also shown to profoundly inhibit lipogenesis through increased phosphorylation of acetyl-CoA carboxylase (ACC). Thus it appears that in addition to regulating lipogenesis, AMPK also plays an important antilipolytic role by regulating HSL in rat adipocytes.

MeSH terms

  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase / antagonists & inhibitors
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Aminoimidazole Carboxamide / analogs & derivatives*
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Enzyme Activation
  • In Vitro Techniques
  • Lipids / biosynthesis*
  • Lipolysis / drug effects*
  • Multienzyme Complexes / metabolism*
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases*
  • Rats
  • Ribonucleotides / pharmacology*

Substances

  • Lipids
  • Multienzyme Complexes
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase
  • AICA ribonucleotide