Acute dexamethasone-induced increase in cardiac lipoprotein lipase requires activation of both Akt and stress kinases

Girish Kewalramani, Prasanth Puthanveetil, Suk Kim Min, Fang Wang, Vivian Lee, Nathania Hau, Elham Beheshti, Natalie Ng, Ashraf Abrahani, Brian Rodrigues

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Following dexamethasone (DEX), cardiac energy generation is mainly through utilization of fatty acids (FA), with DEX animals demonstrating an increase in coronary lipoprotein lipase (LPL), an enzyme that hydrolyzes lipoproteins to FA. We examined the mechanisms by which DEX augments cardiac LPL. DEX was injected in rats, and hearts were removed, or isolated cardiomyocytes were incubated with DEX (0-8 h), for measurement of LPL activity and Western blotting. Acute DEX induced whole body insulin resistance, likely an outcome of a decrease in insulin signaling in skeletal muscle, but not cardiac tissue. The increase in luminal LPL activity after DEX was preceded by rapid nongenomic alterations, which included phosphorylation of AMPK and p38 MAPK, that led to phosphorylation of heat shock protein (HSP)25 and actin cytoskeleton rearrangement, facilitating LPL translocation to the myocyte cell surface. Unlike its effects in vivo, although DEX activated AMPK and p38 MAPK in cardiomyocytes, there was no phosphorylation of HSP25, nor was there any evidence of F-actin polymerization or an augmentation of LPL activity up to 8 h after DEX. Combining DEX with insulin appreciably enhanced cardiomyocyte LPL activity, which closely mirrored a robust elevation in phosphorylation of HSP25 and F-actin polymerization. Silencing of p38 MAPK, inhibition of PI 3-kinase, or preincubation with cytochalasin D prevented the increases in LPL activity. Our data suggest that, following DEX, it is a novel, rapid, nongenomic phosphorylation of stress kinases that, together with insulin, facilitates LPL translocation to the myocyte cell surface.

Original languageEnglish
Pages (from-to)E137-E147
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number1
StatePublished - Jul 2008


  • Actin cytoskeleton
  • Adenosine monophosphate-activated protein kinase
  • Fatty acids
  • Heart


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