A High Fat Diet Increases Plasma Ceramides and Leads to Depressive‐Like Behavior in Female Rats
Authors: Bronfen‐Quinones Samuel A. N. I. , Ramos‐Ortolaza Dinah L. , Gonzalez Agnes P. , Rodriguez Christine , Appleyard Caroline , Haughey Norman J. , Chompre Gladys 
Published: June 2021

Ceramides are a family of lipids that are present in the cellular membrane. Elevated concentrations of ceramides have been strongly associated with depression in humans. Depression has also been linked to obesity. Since a high‐fat diet increases the chances of obesity, a significant increase in ceramides may be accountable for depression in humans.AIMThe aim of this project is to assess how a high‐fat diet contributes to depressive‐like behavior in rats, and to establish a correlation with ceramide amounts in blood plasma. We hypothesize that a high‐fat diet will influence the production of ceramides in the blood plasma and induce depressive‐like behavior in rats. Given the fact that prevalence of depressive disorders and obesity varies between men and women, we decided to incorporate gender‐based groups in our research model.METHODSThree‐week‐old male and female Sprague Dawley rats were fed on a low‐fat diet (10% fat) for six weeks. At the end of that period, animals were separated in two main groups: an experimental group fed with a high fat diet (60% fat) and a control group continued to be fed with a low‐fat diet. After eight weeks, the Forced Swim Test (FST) was performed to assess depressive‐like behavior in the rats. Blood samples were drawn for analysis of ceramide content.RESULTSFemale rats in a high‐fat diet showed higher immobility time during the FST in comparison to female rats fed with a low‐fat diet (p=0.01), showing depressive‐like behavior. Preliminary data on males showed no significant differences in immobility during the FST when fed with either low or high‐fat diet. Blood analysis showed an increase in ceramides C18:1 and C20:0 only in animals fed with a high‐fat diet. Further analysis showed a significant correlation between the observed increase in ceramides and the increase in immobility. This correlation was observed in the female rats fed with a high fat diet, suggesting that the depressive‐like behavior shown by these animals could be mediated by these ceramides. This is further supported by studies showing increases of ceramides in humans suffering from Major Depressive Disorder.CONCLUSIONTaken together, our results suggest that a high‐fat diet can contribute to depressive‐like behavior in female rats, which could, in turn, be due to increases in ceramide levels. Although the increase in ceramides was also observed in males fed on a high fat diet, technical issues with the FST did not allow us to draw any conclusions regarding depressive‐like behavior in these animals. Additional studies are needed to determine whether higher ceramide levels can contribute to a depressive‐like behavior in male rats as well. Our data suggests a low fat‐diet as a parallel supplementary option together with antidepressants may present itself as an alternative for the treatment of major depressive disorder in humans.Support or Funding InformationSupported by NIGMS/INBRE P20 GM103475‐14 and RCMI G12 MD007579This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.