Journal article
Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding
Cardiovascular research, Vol.82(2), pp.351-360
05/01/2009
DOI: 10.1093/cvr/cvp017
PMCID: PMC2675931
PMID: 19147655
Abstract
Aims
Diet-induced obesity is associated with increased myocardial fatty acid (FA) utilization, insulin resistance, and cardiac dysfunction. The study was designed to test the hypothesis that impaired glucose utilization accounts for initial changes in FA metabolism.
Methods and results
Ten-week-old C57BL6J mice were fed a high-fat diet (HFD, 45% calories from fat) or normal chow (4% calories from fat). Cardiac function and substrate metabolism in isolated working hearts, glucose uptake in isolated cardiomyocytes, mitochondrial function, insulin-stimulated protein kinase B (Akt/PKB) and Akt substrate (AS-160) phosphorylation, glucose transporter 4 (GLUT4) translocation, pyruvate dehydrogenase (PDH) activity, and mRNA levels for metabolic genes were determined after 2 or 5 weeks of HFD. Two weeks of HFD reduced basal rates of glycolysis and glucose oxidation and prevented insulin stimulation of glycolysis in hearts and reduced insulin-stimulated glucose uptake in cardiomyocytes. Insulin-stimulated Akt/PKB and AS-160 phosphorylation were preserved, and PDH activity was unchanged. GLUT4 content was reduced by 55% and GLUT4 translocation was significantly attenuated. HFD increased FA oxidation rates and myocardial oxygen consumption (MVO2), which could not be accounted for by mitochondrial uncoupling or by increased expression of peroxisome proliferator activated receptor-α (PPAR-α) target genes, which increased only after 5 weeks of HFD.
Conclusion
Rates of myocardial glucose utilization are altered early in the course of HFD because of reduced GLUT4 content and GLUT4 translocation despite normal insulin signalling to Akt/PKB and AS-160. The reciprocal increase in FA utilization is not due to PPAR-α-mediated signalling or mitochondrial uncoupling. Thus, the initial increase in myocardial FA utilization in response to HFD likely results from impaired glucose transport that precedes impaired insulin signalling.
Details
- Title: Subtitle
- Mechanisms for increased myocardial fatty acid utilization following short-term high-fat feeding
- Creators
- Jordan J Wright - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USAJaetaek Kim - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USAJonathan Buchanan - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USASihem Boudina - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USASandra Sena - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USAKyriaki Bakirtzi - 3 Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USAOlesya Ilkun - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USAHeather A Theobald - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USARobert C Cooksey - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USAKostantin V Kandror - 3 Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USAE. Dale Abel - 1 Division of Endocrinology, Metabolism and Diabetes and Program in Molecular Medicine, University of Utah School of Medicine, 15 N 2030 East, Bldg 533, Rm 3110B, Salt Lake City, UT 84112, USA
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.82(2), pp.351-360
- DOI
- 10.1093/cvr/cvp017
- PMID
- 19147655
- PMCID
- PMC2675931
- NLM abbreviation
- Cardiovasc Res
- ISSN
- 0008-6363
- eISSN
- 1755-3245
- Publisher
- Oxford University Press
- Language
- English
- Date published
- 05/01/2009
- 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
- 9984024533702771
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