Vascular effects of disrupting endothelial mTORC1 signaling in obesity. Am J Physiol Regul Integr Comp Physiol 2021 Aug 01;321(2):R228-R237
Date
07/01/2021Pubmed ID
34189960Pubmed Central ID
PMC8409911DOI
10.1152/ajpregu.00113.2021Scopus ID
2-s2.0-85112009191 (requires institutional sign-in at Scopus site) 4 CitationsAbstract
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 used 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 mo 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 mo) 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.
Author List
Reho JJ, Guo DF, Beyer AM, Wegman-Points L, Pierce GL, Rahmouni KAuthors
Andreas M. Beyer PhD Professor in the Medicine department at Medical College of WisconsinJohn J. Reho Research Scientist II in the Physiology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAorta, Thoracic
Case-Control Studies
Diet, High-Fat
Dietary Sucrose
Disease Models, Animal
Endothelium, Vascular
Humans
Male
Mechanistic Target of Rapamycin Complex 1
Mesenteric Arteries
Mice
Mice, Inbred C57BL
Mice, Knockout
Obesity
Regulatory-Associated Protein of mTOR
Signal Transduction
Subcutaneous Fat
Vasodilation
