Using positron emission tomography to study human ketone body metabolism: A review

Bouteldja, Nadia; Andersen, Lone Thing; Møller, Niels; Gormsen, Lars Christian

doi:10.1016/j.metabol.2014.08.001

Cited by 19 publications

(16 citation statements)

References 74 publications

(112 reference statements)

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“…Free fatty acids serve as a substrate for ketosis in the hepatocytes, where the ultimate products KB are secreted. 37 Cerebral KB transfer is regulated by the monocarboxylic acid transporters 1 (MCT1). 36 Our data in TBI subjects are in line with previous findings in healthy volunteers, 32 demonstrating a very close link between brain and blood KB and indicate that circulating plasma ketones are the main source of cerebral KB supplementation following TBI.…”

Section: Modulation Of Brain Kb By Nutritional Ketosismentioning

confidence: 99%

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Bernini

Masoodi

Solari

et al. 2018

J Cereb Blood Flow Metab

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Adaptive metabolic response to injury includes the utilization of alternative energy substrates -such as ketone bodies (KB) -to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n ¼ 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and b-hydroxybutyrate). Nutrition -from fasting vs. stable nutrition state -was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] mmol/L vs. 13.1 [6.5-64.3] mmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] mmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p ¼ 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.

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Section: Modulation Of Brain Kb By Nutritional Ketosismentioning

confidence: 99%

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Bernini

Masoodi

Solari

et al. 2018

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…Ketones such as beta-hydroxybutyrate and acetoacetate are synthesized in the liver from fatty acids during prolonged fasting, starvation and severe carbohydrate restriction. Under such conditions, up to 60 % of brain energy requirements may be derived from ketone metabolism [ 113 ], whereas ketogenic diets can more or less restore brain energy metabolism and prevent epileptic seizures in patients with GLUT1 deficiency who are unable to transport glucose into the brain [ 114 , 115 ]. However, because insulin suppresses the production of ketones, the brain is usually unable to use this source of energy during insulin-induced hypoglycemia [ 116 ].…”

Section: Cerebral Nutrient Transport Capacity and Hypoglycemiamentioning

confidence: 99%

Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies

Rooijackers

Wiegers

Tack

et al. 2015

Cell. Mol. Life Sci.

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Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain’s handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

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“…This predicament reflects the poor understanding of the exact molecular mechanisms involved in the onset and pathogenesis of GBM. An important aspect of the pathogenesis of GBM lies in the malignant transformation resulting from the accumulation of genetic alterations and abnormal intracellular signaling pathways and growth factors (2)(3)(4)(5). Aberrant proliferation of glioma cells is mediated by the combination of growth factors, including vascular endothelial growth factor, brain-derived neurotrophic factor, platelet-derived growth factor, hepatocyte growth factor and transforming growth factor-β (TGF-β) (6,7).…”

Section: Introductionmentioning

confidence: 99%

SIRT6 suppresses glioma cell growth via induction of apoptosis, inhibition of oxidative stress and suppression of JAK2/STAT3 signaling pathway activation

et al. 2015

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Sirtuin 6 (SIRT6) is a member of the mammalian NAD+‑dependent deacetylase sirtuin family that acts to maintain genomic stability and to repress genes. SIRT6 has recently been reported to be a tumor suppressor that controls cancer metabolism, although this effect of SIRT6 is still in dispute. Moreover, the role of SIRT6 in glioma is largely unknown. In the present study, we found that overexpression of SIRT6 using an adenovirus inhibited glioma cell growth and induced marked cell injury in two glioma cell lines (U87‑MG and T98G). Fluorescent terminal deoxyribonucleotidyl transferase (TdT)‑mediated biotin‑16‑dUTP nick‑end labelling (TUNEL) assay showed that SIRT6 overexpression induced obvious apoptosis in the T98G glioma cells. Immunoblotting and immunofluorescent staining demonstrated that SIRT6 overexpression promoted the mitochondrial-to‑nuclear translocation of apoptosis‑inducing factor (AIF), a potent apoptosis inducer. Moreover, we found that SIRT6 overexpression largely reduced oxidative stress and suppressed the activation of the JAK2/STAT3 signaling pathway in glioma cells. Finally, we showed that SIRT6 mRNA and protein levels in human glioblastoma multiforme tissues were significantly lower than the levels in peritumor tissues. In summary, our data suggest that SIRT6 suppresses glioma cell growth via induction of apoptosis, inhibition of oxidative stress and inhibition of the activation of the JAK2/STAT3 signaling pathway. These results indicate that SIRT6 may be a promising therapeutic target for glioma treatment.

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Using positron emission tomography to study human ketone body metabolism: A review

Cited by 19 publications

References 74 publications

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Modulation of cerebral ketone metabolism following traumatic brain injury in humans

Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies

SIRT6 suppresses glioma cell growth via induction of apoptosis, inhibition of oxidative stress and suppression of JAK2/STAT3 signaling pathway activation

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