A recent study in PNAS investigated whether inorganic nitrates can prevent steatosis of liver using cell and animal models.
Increasing age and unhealthy dietary habits are risk factors for obesity and type 2 diabetes, both of which contribute to the development and progression of cardiovascular disease. Additionally, obesity and type 2 diabetes can also induce steatosis of liver (fatty liver disease), a condition characterized by the accumulation of fat in the liver.
Over time, a fatty liver has the potential of progressing into a more serious complication such as liver cirrhosis (scarring and fibrosis) or cancer, both of which are life-threatening conditions. Researchers are actively investigating and identifying novel methods of reducing the risk of liver steatosis. This is particularly important considering that the condition is highly prevalent, affecting up to 25% of all Americans and moreover, there is currently no approved therapeutic drug available for fatty liver disease.
In a recent study, published in PNAS, researchers from the Karolinska Institutet in Sweden investigated the potential benefits of inorganic nitrates on liver steatosis. Specifically, they used human liver cells, as well as a 3-dimensional liver model, to show that nitrate treatment significantly reduced metabolic- and drug-induced steatosis.
Furthermore, the authors demonstrated that mice given a high-fat and sugar-rich Western diet supplemented with nitrate exhibited a significantly reduced proportion of fat in the liver. Moreover, diabetic mice supplemented with nitrates exhibited reduced blood pressure and improved insulin and glucose homeostasis. Collectively, these findings demonstrate that dietary nitrates significantly reduced fatty liver disease in cell models and mice.
In conclusion, the current study suggests that the incorporation of food rich in inorganic nitrates, like leafy green vegetables, may help reduce the risk of fatty liver disease. In the future, the authors plan on conducting clinical trials to validate the potential beneficial role of nitrate supplementation on liver steatosis in a human cohort.
Previous studies have already shown that dietary nitrates from vegetables can improve mitochondrial efficiency, physical endurance, cardiovascular function, and diabetes. These beneficial roles are thought to be mediated through the formation of nitric oxide species, which help reduce oxidative stress and improve cardiac metabolism.
While the exact mechanisms through which nitrates prevent liver steatosis remain to be validated and more comprehensively studied, clinicians and healthcare providers should encourage patients to include green leafy vegetables in their diets in order to reduce the risk of fatty liver disease.
Written by Haisam Shah, BSc
Reference: Cordero-Herrera, I., Kozyra, M., Zhuge, Z., Haworth, S. M., Moretti, C., Peleli, M., … &Kleschyov, A. L. (2019). AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis. Proceedings of the National Academy of Sciences, 116(1), 217-226.