Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36
journal contributionposted on 2014-04-15, 00:00 authored by Andrew N. Carley, Jian Bi, Xuerong Wang, Jason R. B. Dyck, J. Michael O’Donnell, E. Douglas Lewandowski
Cardiac triacylglycerol (TAG) stores buffer the intracellular availability of long chain fatty acid (LCFA) that act as nuclear receptor ligands, substrate for lipotoxic derivatives, and high energy-yield fuel. The kinetic characteristics of TAG turnover and homeostatic mechanisms linking uptake and storage dynamics in hearts have until now remained elusive. This work examines TAG pool dynamics in the intact beating heart, under normal conditions and in response to acute gene-expression induced changes in CD36. Dynamic mode 13C NMR elucidated multiple kinetic processes in 13C-palmitate incorporation into TAG: an initial, saturable exponential component and a slower linear rate. While previous work indicates the linear component to reflect TAG turnover, we hypothesized the saturable exponential to reflect transport of LCFA across the sarcolemma. Thus, we overexpressed the LCFA transporter, CD36 through cardiac-specific adenoviral infection in vivo. Within 72 hours, CD36 expression was increased 40% in intact hearts, accelerating the exponential phase relative to PBS infused hearts. In response to induced CD36 expression, TAG turnover also increased with elevations in ATGL a modest increase in DGAT1. The results demonstrate a dynamic system of reciprocal gene regulation that couples saturable LCFA uptake across the sarcolemma to TAG synthesis / lipolysis rates.
This work was supported by National Institutes of Health (NIH) grants R37HL49244 and R01HL72702.
Publisher StatementThis research was originally published in Journal of Lipid Research. Carley AN, Bi J, Wang X, Banke NH, Dyck JR, O'Donnell JM, Lewandowski ED. Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36. Journal of Lipid Research. 2012. © the American Society for Biochemistry and Molecular Biology
PublisherAmerican Society for Biochemistry and Molecular Biology