Angiotensin II Alters Mitochondrial Membrane Potential and Lipid Metabolism in Rat Colonic Epithelial Cells
Darby D. Toth,
Christopher L. Souder,
Sarah Patuel,
Cole D. English,
Isaac Konig,
Emma Ivantsova,
Wendi Malphurs,
Jacqueline Watkins,
Kaylie Anne Costa,
John A. Bowden,
Jasenka Zubcevic,
Christopher J. Martyniuk
Affiliations
Darby D. Toth
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Christopher L. Souder
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Sarah Patuel
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Cole D. English
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Isaac Konig
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Emma Ivantsova
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Wendi Malphurs
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Jacqueline Watkins
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Kaylie Anne Costa
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
John A. Bowden
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
Jasenka Zubcevic
Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH 43614, USA
Christopher J. Martyniuk
Department of Physiological Sciences, Center for Environmental and Human Toxicology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA
An over-active renin-angiotensin system (RAS) is characterized by elevated angiotensin II (Ang II). While Ang II can promote metabolic and mitochondrial dysfunction in tissues, little is known about its role in the gastrointestinal system (GI). Here, we treated rat primary colonic epithelial cells with Ang II (1–5000 nM) to better define their role in the GI. We hypothesized that Ang II would negatively affect mitochondrial bioenergetics as these organelles express Ang II receptors. Ang II increased cellular ATP production but reduced the mitochondrial membrane potential (MMP) of colonocytes. However, cells maintained mitochondrial oxidative phosphorylation and glycolysis with treatment, reflecting metabolic compensation with impaired MMP. To determine whether lipid dysregulation was evident, untargeted lipidomics were conducted. A total of 1949 lipids were detected in colonocytes spanning 55 distinct (sub)classes. Ang II (1 nM) altered the abundance of some sphingosines [So(d16:1)], ceramides [Cer-AP(t18:0/24:0)], and phosphatidylcholines [OxPC(16:0_20:5(2O)], while 100 nM Ang II altered some triglycerides and phosphatidylserines [PS(19:0_22:1). Ang II did not alter the relative expression of several enzymes in lipid metabolism; however, the expression of pyruvate dehydrogenase kinase 2 (PDK2) was increased, and PDK2 can be protective against dyslipidemia. This study is the first to investigate the role of Ang II in colonic epithelial cell metabolism.
