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Inhibition of cardiac lipoprotein utilization by transgenic overexpression of Angptl4 in the heart
Abstract
To investigate the role of Angptl4, an inhibitor of lipoprotein lipase that is induced by >3-fold in the heart after rosiglitazone treatment, we generated transgenic mice that overexpress Angptl4 in the heart (MHC-Angptl4). We show that MHC-Angptl4 mice exhibit cardiac-restricted expression of the transgene and inhibition of cardiac lipoprotein lipase (LPL) activity. However, LPL activities in other tissues or that released into plasma by heparin are not affected. In addition, MHC-Angptl4 mice also exhibit hypertriglyceridemia after 6 h of fasting. We use echocardiography to show that MHC-Angptl4 mice develop left-ventricular dysfunction. Comparison of the metabolic profiles of isolated working hearts demonstrates that cardiac impairment in MHC-Angptl4 mice is positively associated with decreased triglyceride (TG) utilization. When bred to transgenic mice that overexpress acyl-CoA synthetase in the heart, a strain that exhibits elevated cardiac TG accumulation, cardiac TG content in double transgenic mice is reversed to that of wild-type mice. Taken together, our data support the hypothesis that induction of Angptl4 in the heart inhibits lipoprotein-derived fatty acid delivery. This mouse model will be useful to elucidate the role of reduced fatty acid supply in the pathogenesis of heart failure and related disorders.
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In mice, overexpression of ANGPTL4 reduces triglyceride uptake into the heart and protects against oxidative stress after either oral fat loading or high-fat diet feeding.
“In mice, overexpression of ANGPTL4 reduces triglyceride uptake into the heart and protects against oxidative stress after either oral fat loading or high-fat diet feeding (27, 79).”
From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [27]
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Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8
Sylvers-Davie, K. L., & Davies, B. S. J. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00195.2021 · Cited by 154
Angptl4 serves as an endogenous inhibitor of intestinal lipid digestion
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Hepatokines—A novel group of exercise factors
Weigert, C., Hoene, M., & Plomgaard, P. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2216-y · Cited by 57
Metadata
- Authors
- Yu, X., Burgess, S. C., Ge, H., Wong, K. K., Nassem, R. H., Garry, D. J., Sherry, A. D., Malloy, C. R., Berger, J. P., & Li, C.
- Affiliations
- Department of Physiology, Touchstone Center for Diabetes Research, Department of Radiology, Mary Nell and Ralph B. Rogers NMR Center, and Departments of Internal Medicine and Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390; and Department of Metabolic Disorders, Merck Research Laboratories, 126 East Lincoln Avenue, Rahway, NJ 07065
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-01-19
- Volume
- 102
- Issue
- 5
- Pages
- 1767-1772
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 94
- References
- 2
- Language
- en
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