Effects of sleep fragmentation and high-fat diet on prostate pathology in mouse models
Abstract
Introduction: Benign Prostate Hyperplasia (BPH) poses a significant health burden among aging males, impacting urinary function and quality of life. While the etiology of BPH is multifactorial, emerging evidence suggests that lifestyle factors such as sleep quality and dietary habits play crucial roles in its pathogenesis. Sleep fragmentation, a common occurrence driven by factors like shift work, stress, and age-related sleep disturbances, has drawn attention for its association with various adverse health outcomes. Individuals with BPH may experience sleep fragmentation due to the need to wake up frequently during the night to urinate, further disrupting their sleep patterns. Chronic sleep fragmentation induces systemic inflammation, which may worsen prostatic inflammation, promote fibrosis development and contribute to BPH progression. Moreover, high-fat diet can induce systemic inflammation and alter hormonal profiles, potentially influencing prostate tissue remodeling and hyperplasia. This study aimed to determine the impacts of sleep fragmentation and high-fat diet on BPH-related pathologies using mouse models. We aimed to provide insight into the underlying mechanisms linking lifestyle factors to BPH pathogenesis by characterizing immune cell infiltration, collagen accumulation, and lipid droplet deposition in prostate tissue.
Methods: Sleep fragmentation was conducted on three-month-old black 6 (C57BL/6J) mice in a sleep fragmentation chamber with a rod moving every two minutes during sleep period, from 6am-6pm, for three months. To explore the impact of a high-fat diet on benign prostatic hyperplasia (BPH), two-month-old mice were fed with a high-fat diet comprising 60% fat, 20% protein, and 20% carbohydrates for a duration of 4 months. Control mice were maintained on a standard diet. Immunohistochemistry (IHC) with CD45 antibody was employed to evaluate immune cell infiltration in the anterior, dorsal, ventral, and lateral prostate lobes. Collagen accumulation was assessed using Picrosirius staining (PSR) for sleep fragmentation groups, while lipid droplets were analyzed using Oil Red O staining for high-fat diet groups. Statistical analysis was performed using the Mann-Whitney test.
Results: In mice with sleep fragmentation, significant elevation in CD45-positive immune cells was observed across all prostate regions compared to sham groups (p < 0.05). However, collagen accumulation was not changed significantly. In mice subjected to a high-fat diet, a significant increase in CD45-positive immune cells was observed in all prostate regions compared to controls (p < 0.001). Lipid droplet accumulation was significantly higher in the ventral (2.44-fold, p < 0.05) and anterior prostate (3.19-fold, p < 0.05) compared to sham groups, indicative of metabolic perturbations induced by high-fat diet. Collagen level was only significantly elevated in the lateral lobe (1.28-fold, p<0.05).
Conclusion: Our findings indicate that both sleep fragmentation and high-fat diet contribute to inflammation in mouse models, as evidenced by increased immune cell infiltration and tissue remodeling. Additionally, a high-fat diet induces notable lipid metabolic alterations and influences the development of fibrosis. These results underscore the complex interplay between lifestyle factors and BPH pathogenesis.