Angiotensin II Alters Mitochondrial Membrane Potential and Lipid Metabolism in Rat Colonic Epithelial Cells

Area of Science:

• Gastroenterology
• Mitochondrial Biology
• Metabolic Research

Background:

• The renin-angiotensin system (RAS) is overactive in many conditions, characterized by elevated angiotensin II (Ang II).
• Ang II is known to cause metabolic and mitochondrial dysfunction in various tissues.
• Its specific role in the gastrointestinal (GI) system, particularly colonic epithelial cells, remains largely unexplored.

Purpose of the Study:

• To investigate the effects of Ang II on the metabolism of primary rat colonic epithelial cells.
• To determine if Ang II negatively impacts mitochondrial bioenergetics in colonocytes.
• To explore potential lipid dysregulation induced by Ang II in the colon.

Main Methods:

• Primary rat colonic epithelial cells were treated with varying concentrations of Ang II (1-5000 nM).
• Cellular ATP production and mitochondrial membrane potential (MMP) were measured.
• Untargeted lipidomics was employed to analyze lipid profiles.
• Gene expression of key enzymes in lipid metabolism was assessed.

Main Results:

• Ang II treatment increased cellular ATP production but decreased MMP in colonocytes.
• Despite impaired MMP, cells maintained mitochondrial oxidative phosphorylation and glycolysis, indicating metabolic compensation.
• Lipidomics revealed alterations in sphingosines, ceramides, triglycerides, and phosphatidylcholines at different Ang II concentrations.
• Pyruvate dehydrogenase kinase 2 (PDK2) expression was increased, potentially offering protection against dyslipidemia.

Conclusions:

• Ang II significantly influences colonic epithelial cell metabolism, affecting both energy production and lipid profiles.
• The colonocytes exhibit compensatory mechanisms to maintain bioenergetics despite Ang II-induced mitochondrial dysfunction.
• This research provides the first insights into the role of Ang II in colonic epithelial cell metabolism and lipid regulation.