Work

Uncoupling Protein 2 and Nitric Oxide Deficiency Favor Glycolytic Pathways and Organ Growth in the Rat Spleen

Year: 2026

Type: article

Abstract: Uncoupling protein 2 (UCP2) is expressed in various tissues throughout the body, but its expression in the spleen exceeds that of other organs. However, the precise function of UCP2 for spleen physiology is unclear. The spleen acts as a hub connecting the nervous system and immune system to cardiovascular and metabolic diseases. Here, we analyzed the impact of hypertension on the spleen and the role of UCP2 in this process. Experiments were performed with UCP2-knockout rats and their wild-type littermates. Hypertension was induced by administering the nitric oxide inhibitor L-NAME via tap water. Genetic depletion of UCP2 increased spleen size (splenomegaly) and strongly impaired the expression of genes coding for mitochondrial proteins. Among them, genes coding for proteins involved in oxidative metabolism, such as pyruvate dehydrogenase alpha 1, and the detoxification of reactive oxygen species were down-regulated. Collectively, these alterations in metabolism favor glycolysis and proliferation. Moreover, NOS3 was among the strongest down-regulated genes in UCP2−/− rats, and the inhibition of nitric oxide synthase by L-NAME mimicked large parts of the expression profile. Neither the depletion of UCP2 nor L-NAME-induced hypertension or combinations thereof affected chronic inflammation. In summary, UCP2 controls fuel consumption in splenic cells in a nitric-oxide-dependent way.

Source: Current Issues in Molecular Biology

DOI: 10.3390/cimb48080775