Psychological trauma and obesity co-occur frequently and have been identified as major risk factors for psychiatric disorders. Surprisingly, preclinical studies examining how obesity disrupts the ability of the brain to cope with psychological trauma are lacking. The objective of this study was to determine whether an obesogenic Western-like high-fat diet (WD) predisposes rats to posttraumatic stress responsivity. Adolescent Lewis rats (postnatal day, PND, 28) were fed ad libitum for eight weeks with either the experimental WD diet (41.4% kcal from fat) or the control diet (16.5% kcal from fat). We modeled psychological trauma by exposing young adult rats to a cat odor threat. The elevated plus maze and the open field test revealed increased psychological trauma-induced anxiety-like behaviors in the rats that consumed the WD when compared to control animals one-week posttraumatic stress (p < 0.05). Magnetic resonance imaging showed significant hippocampal atrophy (20% reduction) and lateral ventricular enlargement (50% increase) in the animals fed the WD when compared to controls. These volumetric abnormalities were associated with behavioral indices of anxiety, increased leptin and FKBP51 protein levels, and reduced hippocampal blood vessel density. We found asymmetric structural vulnerabilities to the WD, particularly the ventral and left hippocampus and lateral ventricle. This study highlights how WD consumption during adolescence impacts key substrates implicated in posttraumatic stress disorder (PTSD). Understanding how consumption of a WD affects the developmental trajectories of the stress neurocircuitry is critical, as stress susceptibility imposes a marked vulnerability to neuropsychiatric disorders.
Significance Statement: Psychological trauma and obesity are highly prevalent in adolescents. However, preclinical studies investigating how obesity alters psychological trauma responsivity are lacking. In this study, we report that adolescent rats consuming a typical obesogenic Western high-fat diet (WD) display exaggerated posttraumatic stress reactions during early adulthood, along with increased hippocampal expression of the posttraumatic stress biomarker, FKBP51. We reveal distinctive hippocampal and ventricular volumetric abnormalities potentially underlying the effects of the WD in maladaptive stress responsiveness. We anticipate that this study will inform the path to needed biomarkers and interventions for improving the quality of stress and anxiety management, particularly in a growing overweight and obese population.
The Authors report no conflict of interest.
Loma Linda University Seed Grant Funds.