Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction

Ayanna S Augustus; Jonathan Buchanan; Tae-Sik Park; Kumiko Hirata; Hye-lim Noh; Jie Sun; Shunichi Homma; Jeanine D'armiento; E. Dale Abel; Ira J Goldberg

doi:10.1074/jbc.M509890200

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Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction

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Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction

Ayanna S Augustus, Jonathan Buchanan, Tae-Sik Park, Kumiko Hirata, Hye-lim Noh, Jie Sun, Shunichi Homma, Jeanine D'armiento, E. Dale Abel and Ira J Goldberg

The Journal of biological chemistry, Vol.281(13), pp.8716-8723

03/31/2006

DOI: 10.1074/jbc.M509890200

PMID: 16410253

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Abstract

Long-chain fatty acids (FAs) are the predominant energy substrate utilized by the adult heart. The heart can utilize unesterified FA bound to albumin or FA obtained from lipolysis of lipoprotein-bound triglyceride (TG). We used heart-specific lipoprotein lipase knock-out mice (hLpL0) to test whether these two sources of FA are interchangeable and necessary for optimal heart function. Hearts unable to obtain FA from lipoprotein TG were able to compensate by increasing glucose uptake, glycolysis, and glucose oxidation. HLpL0 hearts had decreased expression of pyruvate dehydrogenase kinase 4 and increased cardiomyocyte expression of glucose transporter 4. Conversely, FA oxidation rates were reduced in isolated perfused hLpL0 hearts. Following abdominal aortic constriction expression levels of genes regulating FA and glucose metabolism were acutely up-regulated in control and hLpL0 mice, yet all hLpL0 mice died within 48 h of abdominal aortic constriction. Older hLpL0 mice developed cardiac dysfunction characterized by decreased fractional shortening and interstitial and perivascular fibrosis. HLpL0 hearts had increased expression of several genes associated with transforming growth factor-beta signaling. Thus, long term reduction of lipoprotein FA uptake is associated with impaired cardiac function despite a compensatory increase in glucose utilization.

Details

Title: Subtitle: Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction
Creators: Ayanna S Augustus
Jonathan Buchanan
Tae-Sik Park
Kumiko Hirata
Hye-lim Noh
Jie Sun
Shunichi Homma
Jeanine D'armiento
E. Dale Abel
Ira J Goldberg
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.281(13), pp.8716-8723
DOI: 10.1074/jbc.M509890200
PMID: 16410253
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 03/31/2006
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024421102771

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