Diesel exhaust exposure leads to disarray in liver function in mice; could also indicate health issues for humans

UCLA Health researchers have discovered significant changes in liver function following exposure to diesel exhaust (DE) in a controlled study involving mice. The study identified disrupted activity in 658 genes and 118 metabolites. These changes led to a higher production of triglycerides, fatty acids, and sugars, largely due to problems with mitochondria, an organelle in the cell responsible for energy production.

The research is published in the journal Particle and Fibre Toxicology.

The researchers also exposed liver cells to diesel particles and confirmed that the particles were sufficient to activate a gene called Pck1, which led to increased glucose production. Taking it one step further, the researchers inhibited Pck1 to tease out its function. This step reduced glucose levels, confirming Pck1’s role in glucose production.

DE emissions play a large role in air pollution and its links to type 2 diabetes, fatty liver disease, cardiovascular diseases, and cancer. Previous research by the same investigators had shown that diesel particles cause mitochondrial dysfunction in liver tissue cells, but the researchers wanted to study the effects in mice. This is the first study to demonstrate the ability of DE exposure to induce mitochondrial dysfunction in vivo.

While there is emerging evidence of a connection between air pollution exposure and metabolic diseases, the exact mechanisms and genes involved are unknown. The researchers say these findings may indicate some of the factors that cause humans to get fatty liver disease and type 2 diabetes after being exposed to DE. Future research will study whether targeting Pck1 could be a feasible intervention against DE-induced type 2 diabetes.

UCLA Health researchers have discovered significant changes in liver function following exposure to diesel exhaust (DE) in a controlled study involving mice. The study identified disrupted activity in 658 genes and 118 metabolites. These changes led to a higher production of triglycerides, fatty acids, and sugars, largely due to problems with mitochondria, an organelle in the cell responsible for energy production.

The research is published in the journal Particle and Fibre Toxicology.

The researchers also exposed liver cells to diesel particles and confirmed that the particles were sufficient to activate a gene called Pck1, which led to increased glucose production. Taking it one step further, the researchers inhibited Pck1 to tease out its function. This step reduced glucose levels, confirming Pck1’s role in glucose production.

DE emissions play a large role in air pollution and its links to type 2 diabetes, fatty liver disease, cardiovascular diseases, and cancer. Previous research by the same investigators had shown that diesel particles cause mitochondrial dysfunction in liver tissue cells, but the researchers wanted to study the effects in mice. This is the first study to demonstrate the ability of DE exposure to induce mitochondrial dysfunction in vivo.

While there is emerging evidence of a connection between air pollution exposure and metabolic diseases, the exact mechanisms and genes involved are unknown. The researchers say these findings may indicate some of the factors that cause humans to get fatty liver disease and type 2 diabetes after being exposed to DE. Future research will study whether targeting Pck1 could be a feasible intervention against DE-induced type 2 diabetes.