Adiponectin increases LPL activity via RhoA/ROCK-mediated actin remodelling in adult rat cardiomyocytes

Riya Ganguly, Kristin Schram, Xiangping Fang, Minsuk Kim, Brian Rodrigues, Farah S.L. Thong, Gary Sweeney

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Cardiomyocyte substrate utilization is important in maintaining optimal cardiac function. Adiponectin has been shown to confer cardioprotective effects in part via regulating glucose and fatty acid uptake and oxidation in cardiomyocytes. Here we investigated mechanisms whereby adiponectin mediates a particular metabolic effect by focusing on lipoprotein lipase (LPL), an enzyme that increases free fatty acid availability to the heart by breakdown of chylomicrons and verylow-density lipoproteins in circulation.Weused primary adult rat cardiomyocytesanddemonstrate that adiponectin increased LPL translocation to the cell surface where it could be released at least partly in its active form, as evidenced by measuring basal and heparin-releasable LPL activity. Furthermore, these effects of adiponectin were mediated via remodeling of the actin cytoskeleton. We quantitatively assessed the filamentous to globular actin ratio and show that increased stress fiber formation, visualized by rhodamine-phalloidin immunofluorescence, in response to adiponectin, is achieved via stimulating Ras homolog gene family A (RhoA) activity, determined using G-LISA™RhoAactivation assay kit.Wealso demonstrate that adiponectin induces phosphorylation and inhibition of cofilin, leading to a reduction in actin treadmilling. Increased cofilin phosphorylation and stress fiber formation in response to adiponectin were prevented by inhibition of either RhoA or its downstream kinase Rho-associated protein kinase. Importantly, inhibition of cytoskeletal remodeling prevented adiponectin-stimulated plasma membrane LPL content detected by immunofluorescence and also subsequent LPL activity. In summary, we show that adiponectin mediates actin cytoskeleton remodeling to translocate LPL and allow subsequent activation.

Original languageEnglish
Pages (from-to)247-254
Number of pages8
JournalEndocrinology
Volume152
Issue number1
DOIs
StatePublished - Jan 2011

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