Unwinding the interplay between brain and liver in the pathophysiology of brain trauma

Although clinical evidence indicates that TBI has profound effects on peripheral metabolism, TBI research has primarily focused on the CNS. The liver plays a major role in control of homeostasis and pathogenesis, affecting synthesis of lipids and proteins used across the body and brain. Fructose consumption is common in the Western Society and a major cause of metabolic syndrome, diabetes, and obesity. Results showed that fructose consumption in rodents for 3 weeks, under the threshold for establishment of metabolic syndrome, exacerbates the deleterious effects of fluid percussion injury on glucose metabolism, inflammation, and cell energy homeostasis. These effects of TBI and fructose seem to engage the hypothalamic neuroendocrine axis by involving the growth hormone system with resulting effects on a metabolic/inflammatory cascade in the periphery. Fructose fed TBI animals had elevated markers of inflammation (TLR4), lipid peroxidation (4HNE), and reduced markers of cell energy homeostasis (uMitCK) as well as reduced insulin signaling proteins (InR, IRS1) and growth hormone signaling proteins (GHR, IGF-1) in the liver. Fructose also potentiated the action of TBI on hepatic lipid droplet accumulation involving lipid-promoting factors (FAS, LXRα, CD36, ABCA1). Studies in cultured hepatocytes validated the action of growth hormone and fructose on the synthesis of FAS and CD36. TBI affects the transcriptomic profiling in the hypothalamus and several differentially expressed genes that are primarily associated to lipid metabolism providing cues for peripheral alterations in TBI pathology. These results reveal that the effects caused by TBI are not limited to the CNS, and that fructose promotes a stage of metabolic dysfunction that potentiates the effects of TBI on systemic metabolism. RNA samples of hypothalamus from Sham and TBI rats (n=5 per group ) were used for RNA-Seq sequenced in paired-end mode by HiSeq 4000 (Illumina Inc., CA, USA)