title: The human brain produces fructose from glucose.
abstract: Fructose has been implicated in the pathogenesis of obesity and type 2 diabetes. In contrast to glucose, CNS delivery of fructose in rodents promotes feeding behavior. However, because circulating plasma fructose levels are exceedingly low, it remains unclear to what extent fructose crosses the blood-brain barrier to exert CNS effects. To determine whether fructose can be endogenously generated from glucose via the polyol pathway (glucose → sorbitol → fructose) in human brain, 8 healthy subjects (4 women/4 men; age, 28.8 ± 6.2 years; BMI, 23.4 ± 2.6; HbA1C, 4.9% ± 0.2%) underwent1H magnetic resonance spectroscopy scanning to measure intracerebral glucose and fructose levels during a 4-hour hyperglycemic clamp (plasma glucose, 220 mg/dl). Using mixed-effects regression model analysis, intracerebral glucose rose significantly over time and differed from baseline at 20 to 230 minutes. Intracerebral fructose levels also rose over time, differing from baseline at 30 to 230 minutes. The changes in intracerebral fructose were related to changes in intracerebral glucose but not to plasma fructose levels. Our findings suggest that the polyol pathway contributes to endogenous CNS production of fructose and that the effects of fructose in the CNS may extend beyond its direct dietary consumption.
authors.affiliation: Section of Endocrinology and.
authors.forename: Janice J
authors.initials: JJ
authors.lastname: Hwang
authors.affiliation: Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Lihong
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Section of Endocrinology and.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hamza
authors.affiliation: Yale Center for Analytical Sciences, Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Dai
authors.affiliation: Section of Endocrinology and.
authors.forename: Renata
authors.initials: R
authors.lastname: Belfort-DeAguiar
authors.affiliation: Section of Endocrinology and.
authors.forename: Gary
authors.initials: G
authors.lastname: Cline
authors.affiliation: Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rothman
authors.affiliation: Department of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Graeme
authors.initials: G
authors.lastname: Mason
authors.affiliation: Section of Endocrinology and.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D005632:Fructose / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D066244:Proton Magnetic Resonance Spectroscopy; D012044:Regression Analysis; D013012:Sorbitol / Q000378:metabolism; D055815:Young Adult
chemical_list: D005632:Fructose; D013012:Sorbitol; D005947:Glucose