Vascular effects of disrupting endothelial mTORC1 signaling in obesity

Area of Science:

• Cardiovascular Biology
• Metabolic Disease Research
• Endothelial Function

Background:

• The mechanistic target of rapamycin complex 1 (mTORC1) pathway is crucial for cardiovascular health.
• Dysregulation of mTORC1 signaling is linked to cardiovascular diseases.
• Obesity-associated endothelial dysfunction highlights the need to understand vascular signaling pathways.

Purpose of the Study:

• To investigate the role of vascular mTORC1 signaling in obesity-induced endothelial dysfunction.
• To determine if elevated mTORC1 signaling in obesity is a cause or consequence of endothelial impairment.
• To assess the necessity of endothelial mTORC1 signaling for maintaining vascular function during obesity.

Main Methods:

• Utilized mouse models fed high-fat/high-sucrose diets to induce obesity.
• Examined aortic endothelial function and vascular mTORC1 signaling in obese mice.
• Analyzed endothelial cells and visceral adipose vessels from obese human subjects.
• Employing genetic manipulation to delete the Raptor subunit of mTORC1 in endothelial cells.

Main Results:

• Chronic high-fat diet feeding in mice led to endothelial dysfunction and increased vascular mTORC1 signaling.
• Obese human endothelial cells and adipose vessels showed a trend toward elevated mTORC1 signaling.
• Genetic deletion of endothelial mTORC1 (Raptor) did not prevent or rescue diet-induced endothelial dysfunction.
• Endothelial mTORC1 deficiency did not reverse endothelial dysfunction caused by high-fat/high-sucrose diet.

Conclusions:

• Vascular mTORC1 signaling is upregulated in obesity.
• Despite increased signaling, vascular mTORC1 activation is not required for the development of obesity-related endothelial dysfunction.
• Targeting vascular mTORC1 may not be a viable strategy for treating obesity-induced endothelial impairment.