Journal article
Vascular Effects of Disrupting Endothelial mTORC1 (Mechanistic Target of Rapamycin Complex 1) Signaling in Obesity
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.321(2), pp.R228-R237
06/30/2021
DOI: 10.1152/ajpregu.00113.2021
PMCID: PMC8409911
PMID: 34189960
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) signaling complex is emerging as a critical regulator of cardiovascular function with alterations in this pathway implicated in cardiovascular diseases. In this study, we utilized animal models and human tissues to examine the role of vascular mTORC1 signaling in the endothelial dysfunction associated with obesity. In mice, obesity induced by high fat/high sucrose diet feeding for ~2 months resulted in aortic endothelial dysfunction without appreciable changes in vascular mTORC1 signaling. On the other hand, chronic high fat diet feeding (45% or 60% kcal: ~9 months) in mice resulted in endothelial dysfunction associated with elevated vascular mTORC1 signaling. Endothelial cells and visceral adipose vessels isolated from obese humans display a trend toward elevated mTORC1 signaling. Surprisingly, genetic disruption of endothelial mTORC1 signaling through constitutive or tamoxifen inducible deletion of endothelial Raptor (critical subunit of mTORC1) did not prevent or rescue the endothelial dysfunction associated with high fat diet feeding in mice. Endothelial mTORC1 deficiency also failed to reverse the endothelial dysfunction evoked by a high fat/high sucrose diet in mice. Taken together, these data show increased vascular mTORC1 signaling in obesity, but this vascular mTORC1 activation appears not to be required for the development of endothelial impairment in obesity.
Details
- Title: Subtitle
- Vascular Effects of Disrupting Endothelial mTORC1 (Mechanistic Target of Rapamycin Complex 1) Signaling in Obesity
- Creators
- John J Reho - Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesDeng-Fu Guo - Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Obesity Research and Education Initiative, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesAndreas M Beyer - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesLauren Wegman-Points - Department of Health and Human Physiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesGary L Pierce - Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Department of Health and Human Physiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United StatesKamal Rahmouni - Department of Neuroscience and Pharmacology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Obesity Research and Education Initiative, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States, Iowa City Veterans Affairs Health Care System, Iowa City, Iowa, United States
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.321(2), pp.R228-R237
- DOI
- 10.1152/ajpregu.00113.2021
- PMID
- 34189960
- PMCID
- PMC8409911
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Grant note
- DOI: 10.13039/100006108, name: HHS | NIH | National Center for Advancing Translational Sciences, award: UL1TR002537; DOI: 10.13039/100000050, name: HHS | NIH | National Heart, Lung, and Blood Institute, award: HL084207; DOI: 10.13039/100000738, name: U.S. Department of Veterans Affairs, award: BX004249
- Language
- English
- Date published
- 06/30/2021
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology; Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984094984002771
Metrics
15 Record Views