title: Multiphasic triacylglycerol dynamics in the intact heart during acute in vivo overexpression of CD36.
abstract: 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 (13)C NMR elucidated multiple kinetic processes in (13)C-palmitate incorporation into TAG: an initial, saturable exponential component and a slower linear rate. Although 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 h, CD36 expression was increased 40% in intact hearts, accelerating the exponential phase relative to PBS-infused hearts. TAG turnover also increased with elevations in adipose triglyceride lipase (ATGL) and a modest increase in diacylglycerol acyltransferase 1 (DGAT1), without a significant expansion of the intracellular lipid pools. The results demonstrate a dynamic system of reciprocal gene regulation that couples saturable LCFA uptake across the sarcolemma to TAG synthesis/lipolysis rates.
authors.affiliation: Program in Integrative Cardiac Metabolism, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Carley
authors.forename: Jian
authors.initials: J
authors.lastname: Bi
authors.forename: Xuerong
authors.initials: X
authors.lastname: Wang
authors.forename: Natasha H
authors.initials: NH
authors.lastname: Banke
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.forename: J Michael
authors.initials: JM
authors.lastname: O'Donnell
authors.forename: E Douglas
authors.initials: ED
authors.lastname: Lewandowski
mesh_terms: D000105:Acetyl Coenzyme A / Q000096:biosynthesis; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D007700:Kinetics; D008066:Lipolysis / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D018955:CD36 Antigens; D005227:Fatty Acids; D014280:Triglycerides; D000105:Acetyl Coenzyme A