Metabolic-Dysfunction Associated Liver Disease Progresses Independent of Weight in a Rodent Model

Abstract

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is the most prevalent liver disease worldwide with an estimated 25% of U.S. adults having MASLD. MASLD is typically regarded as a diet driven disease, with the Western diet (high fat, high sugar, low fiber) being a major driver. Recently, evidence suggests MASLD can be present regardless of body weight. There is not good evidence on how prevalent this is, but reports suggest it could be as high as nearly 30% of MASLD patients. As such, there is a critical need to better understand MASLD independent of weight to ensure all individuals with the disease are receiving proper diagnosis and treatment. Methods: Young female rats were fed either a Control (AIN-93G) or Western (45% fat, 34% sugar) diet for 8 weeks. Histology, RT-qPCR, and standard biological assays were performed to analyze differences in hepatic function and fatty acid analysis was used to analyze fatty acid deposition in the liver, adipose tissue, and brain. Results: There were no statistically significant differences in the weights of rats consuming a Control or Western diet. However, consuming a Western diet had increased histological evidence of fat deposition and inflammation compared to Control. Rats consuming a Western diet also displayed increased ( p<0.05) hepatic triglyceride content and relative expression of several key genes involved in lipogenesis and oxidative stress. Fatty acid analysis found Western diet rats to have increased (p<0.05) hepatic monounsaturated fatty acid (MUFA) content, while adipose tissue of those same animals had decreased (p<0.05) MUFAs. Conclusions: The Western diet plays a significant role in the development of MASLD independent of differences in weight. This model may serve to better elucidate mechanisms at play in lean MASLD. We are currently conducting additional experiments on the role of alcohol in this phenomenon. WVU Davis College Dean's Opportunity Fund and the UVM Food Systems Research Center. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.