IL‐15 Upregulates GLUT1 while Reducing CPT1 in Cardiomyocytes
Authors: Yim Veronica T , Hennigan Kelly S , Kim Adela M , Tomac Michael P , Abbott Marcia J 
Published: June 2021

Obesity is an exponentially growing epidemic in the United States and is a leading contributor of cardiovascular disease (CVD). Maintenance of lifestyle interventions to prevent and treat obesity, such as diet and exercise, is a challenge. In this regard, targeting the molecular mediators of obesity has become a focus to prevent CVD disease progression. In an undiseased state, the cardiac muscle relies primarily on oxidative processes for energy production. In some cases, CVD can lead to upregulation of glycogenic, rather than oxidative, processes to produce ATP for muscle contraction. The myokine interleukin‐15 (IL‐15) is secreted by skeletal muscle during exercise and has been shown to reduce obesity and related disorders. However, the effects of IL‐15 signaling in cardiomyocytes (CM) remains largely unknown. The objective of the current study was to determine if IL‐15 regulates glucose and/or fatty acid (FA) metabolism in CM. Differentiated CM were treated with 100 ng/mL of IL‐15 for 24 hours. Protein was harvested, from either IL‐15 or vehicle treated cells, and isolated into total, mitochondrial and plasma membrane (PM) fractions. The protein concentration was quantified utilizing a Bradford assay. Subsequently, protein analysis, via Western blotting, was performed. Fifteen micrograms of protein was loaded onto 4–20% polyacrylamide gels for electrophoresis. The proteins were then transferred onto a PVDF membrane. Primary antibodies against GLUT1, GLUT4, and CPT1 (1:1000) were used, followed by secondary antibodies (1:2000). GLUT1 and GLUT4 were analyzed in both total cell fractions and PM fractions, while CPT1 levels were assessed in mitochondrial fractions. The membranes were subjected to enhanced chemiluminescence, imaged and quantified with ImageJ software. A t‐test (P<0.05) was used to determine if IL‐15 had any significant effects on the protein levels of the aforementioned proteins. IL‐15 did not alter total GLUT4, PM GLUT4 or PM GLUT1 (P>0.05). Conversely, IL‐15 treatment resulted in a 367% increase in total GLUT1 protein levels when compared to the vehicle control cells (P<0.05). Of note, IL‐15 decreased mitochondrial CPT1 by nearly 50% (P<0.05). Our data indicate that IL‐15 increases the protein concentration of one of the glucose transporters, GLUT1, and decreases the protein concentration of the mitochondrial FA transporter, CPT1, in CM. Thus, IL‐15 may be responsible for promoting a shift in CM metabolism from FA to glucose utilization. Additional studies are warranted to confirm this proposed shift in metabolism by studying glucose uptake and beta‐oxidation activity in CM. Further, to understand if an IL‐15‐mediated shift in metabolism is beneficial to CM, further studies aimed at assessing cardiac muscle function are required. Taken together, if IL‐15 holds the potential as a treatment for obesity, examination of its functions in various tissues is required.

Support or Funding Information

Chapman University Crean College of Health and Behavioral Sciences Summer Undergraduate Research Fellowship; American Heart Association 16SDG30680003

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.