The liver-brain axis regulates metabolic homeostasis, with glucose metabolism playing a key role. Liver dysfunction, such as fibrosis, may impact brain metabolism and consequently, brain function. Positron emission tomography (PET) imaging provides a non-invasive approach to study glucose metabolism in both organs. A recent longitudinal PET/CT study utilizing 2-deoxy-2-18F-fluoro-d-glucose (18FFDG) amongst other radiotracers revealed significant metabolic changes in the liver in a mouse model of liver fibrosis. Here, we retrospectively analyzed those data to quantify potential associated changes in brain glucose metabolism. Eleven male C57BL/6N mice underwent repeated PET imaging with 18FFDG at baseline, pre-fibrosis, fibrosis, and remission stages. Cerebral glucose metabolism was assessed using standardized uptake value (SUV), blood glucose-corrected SUV (SUVgluc), and kinetic modeling (Patlak and two-tissue compartment models) for calculation of the glucose metabolic rate (MRGlu). Both SUVgluc and MRGlu significantly decreased during pre-fibrosis and fibrosis on whole brain level and recovered at remission. SUVgluc statistical parametric mapping identified multiple brain areas with reduced glucose metabolism, which was confirmed by regional analysis showing progressive reduction in SUVgluc. Correlation analyses confirmed SUVgluc as a reliable surrogate for MRGlu, unlike uncorrected SUV. Liver 18FFDG uptake increased during fibrosis and normalized at remission, mirroring changes in blood glucose concentrations. 18FFDG PET imaging revealed that liver fibrosis alters glucose metabolism in both liver and brain, emphasizing the potential of molecular imaging for future assessment of metabolic interaction between liver and brain. 18FFDG uptake in terms of SUVgluc strongly correlated with MRGlu from kinetic modeling, supporting its utility as a valid surrogate parameter to quantify cerebral glucose metabolism in mice.
Wanek et al. (Thu,) studied this question.