Role of dietary-induced obesity on the sting pathway and related liver inflammation
Embargo Date
2027-11-10
OA Version
Citation
Abstract
The prevalence of obesity has become a large epidemic worldwide. The combination of poor dietary choices and a sedentary lifestyle can lead to the development of obesity. Excessive food and calorie intake can lead to fat accumulation in the human body. More importantly, the accumulation of fat surrounding vital organs like the liver can result in liver inflammation and fibrosis. This study will focus on how liver inflammation and interactions with immune cells can lead to Metabolic Associated Fatty Liver Disease (MAFLD) and further liver failure. Under a normal state, the innate immune system provides the liver with the necessary release of immune cells to repair damaged tissue and clear harmful pathogens. During metabolic dysfunction present in MAFLD, immune cells like neutrophils can become overstimulated. This overstimulation leads to excessive release of the protease neutrophil elastase. In many cases, accumulation of NE resulted in increases in extracellular matrix (ECM), collagen, and proinflammatory cytokines, leading to liver fibrosis. In contrast, studies have shown that NE knockout provided a protective and recovery effect that reduced the damaging effects of obesogenic diets. A potential explanation for this phenomenon can be the association between neutrophil elastase and inflammatory pathways like the cGAS-STING pathway. During this study, Western blotting was utilized to visualize and quantify changes in several biomarkers of STING signaling. Samples were used derived from 4 different groups of mice categorized by diet. The wild-type high-fat diet (HFD) and wild-type high-fat/high-fructose diet (HFHFD) groups were compared with the normal chow diet (NCD) group to detect changes related to metabolic status. The neutrophil elastase knockout/HFHFD group was compared to the wild-type group of the same diet to investigate whether the elimination of NE significantly affected inflammation. The results revealed that regulation of the inflammatory STING pathway is primarily influenced by dietary status while showing prominent recovery in the NEKO group, suggesting that neutrophil elastase removal can prevent the overstimulation of inflammatory processes in metabolic dysfunction.
Description
2024