Short-term fructose ingestion affects the brain independently from establishment of metabolic syndrome

Abstract

Chronic fructose ingestion is linked to the global epidemic of metabolic syndrome (MetS), and poses a serious threat to brain function. We asked whether a short period (one week) of fructose ingestion potentially insufficient to establish peripheral metabolic disorder could impact brain function. We report that the fructose treatment had no effect on liver/body weight ratio, weight gain, glucose tolerance and insulin sensitivity, was sufficient to reduce several aspects of hippocampal plasticity. Fructose consumption reduced the levels of the neuronal nuclear protein NeuN, Myelin Basic Protein, and the axonal growth-associated protein 43, concomitant with a decline in hippocampal weight. A reduction in peroxisome proliferator-activated receptor gamma coactivator-1 alpha and Cytochrome c oxidase subunit II by fructose treatment is indicative of mitochondrial dysfunction. Furthermore, the GLUT5 fructose transporter was increased in the hippocampus after fructose ingestion suggesting that fructose may facilitate its own transport to brain. Fructose elevated levels of ketohexokinase in the liver but did not affect SIRT1 levels, suggesting that fructose is metabolized in the liver, without severely affecting liver function commensurable to an absence of metabolic syndrome condition. These results advocate that a short period of fructose can influence brain plasticity without a major peripheral metabolic dysfunction.

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

“…Increased fructose ingestion correlates with the development of metabolic diseases such as obesity, insulin resistance, T2DM, nonalcoholic fatty liver disease, hypertension, hyperuricemia, and dyslipidemia [ 90 , 93 , 94 ]. Furthermore, results from animal studies suggest that high fructose intake may be linked to cognitive decline derived from insulin resistance, reduced neurogenesis, mitochondrial dysfunction, and a reduction of hippocampal plasticity [ 89 , 90 , 93 , 95 , 96 , 97 , 98 ]. Epidemiological studies have also suggested an association between the consumption of a Western diet (high in saturated fats and added sugars) with cognitive dysfunction in humans [ 99 , 100 ].…”

“…In the brain, GLUT5/Glut5 is expressed in microglia [ 106 ], cerebellar Purkinje cells [ 107 , 108 ], the human BBB [ 103 ], rat hippocampus [ 95 , 109 ], rat cerebral cortex [ 107 , 108 ], rat olfactory bulb [ 108 ], rat optic tract and its terminal fields [ 107 ], and in rat vestibular and cochlear nuclei [ 107 ]. GLUT5 is the sole hexose transporter found in microglia [ 110 ].…”

Brain Trauma Disrupts Hepatic Lipid Metabolism: Blame It on Fructose?

“…After the acclimatization period, the animals were randomly assigned to either regular or fructose (15% w/v) drinking water. It was previously established that 15% fructose for 3 weeks is a suitable stimulus to elicit metabolic disturbances in rats . At 3 weeks of fructose intervention, all animals were subjected to either sham or fluid percussion injury (FPI).…”

Chronic Consumption of Fructose Induces Behavioral Alterations by Increasing Orexin and Dopamine Levels in the Rat Brain

“…Chronic feeding with fructose (4–16 weeks) was reported to induce apoptosis, reduce hippocampal neurogenesis [ 13 ], and impair hypothalamic leptin sensitivity [ 14 ], while increasing oxidative stress and neuroinflammation, and causing down-regulation of the cholinergic system in the hippocampus and cerebral cortex of rats [ 15 ]. Interestingly, recent studies have suggested that shorter periods (1–2 weeks) of fructose intake induce autophagy in rat cerebral cortex, reduce both the hippocampal weight and the expression of molecules related to cellular plasticity, and significantly increase markers of inflammation and oxidative damage in young and adult rats [ 16 , 17 , 18 ].…”