Université de Sherbrooke

About: Université de Sherbrooke is a education organization based out in Sherbrooke, Quebec, Canada. It is known for research contribution in the topics: Population & Receptor. The organization has 14922 authors who have published 28783 publications receiving 792511 citations. The organization is also known as: Universite de Sherbrooke & Sherbrooke University.

Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

Abstract: We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer's disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain's main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain's main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal.

Superconductivity in the noncentrosymmetric half-Heusler compound LuPtBi: A candidate for topological superconductivity

Abstract: We report superconductivity in the ternary half-Heusler compound LuPtBi, with ${T}_{c}=1.0$ K and ${H}_{c2}=1.6$ T. The crystal structure of LuPtBi lacks inversion symmetry, hence the material is a noncentrosymmetric superconductor. Magnetotransport data show semimetallic behavior in the normal state, which is evidence for the importance of spin-orbit interaction. The combination of strong spin-orbit coupling and noncentrosymmetric crystal structure make LuPtBi a strong candidate for 3D topological superconductivity.

Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia.

Abstract: Background The cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer's disease (AD). The ketones, acetoacetate and β-hydroxybutyrate, are the brain's main alternative energy substrates to glucose. Objective To gain insight into brain fuel metabolism in mild AD dementia by determining whether the regional CMR and the rate constant of acetoacetate (CMRa and Ka, respectively) reflect the same metabolic deficit reported for cerebral glucose uptake (CMRg and Kg). Methods Mild AD dementia (Mild AD; n = 10, age 76 y) patients were compared with gender- and age-matched cognitively normal older adults (Controls; n = 29, age 75 y) using a PET/MRI protocol and analyzed with both ROI- and voxel-based methods. Results ROI-based analysis showed 13% lower global CMRg in the gray matter of mild AD dementia versus Controls (34.2 ± 5.0 versus 38.3 ± 4.7 μmol/100 g/min, respectively; p = 0.015), with CMRg and Kg in the parietal cortex, posterior cingulate, and thalamus being the most affected (p ≤ 0.022). Neither global nor regional CMRa or Ka differed between the two groups (all p ≥ 0.188). Voxel-based analysis showed a similar metabolic pattern to ROI-based analysis with seven clusters of significantly lower CMRg in the mild AD dementia group (uncorrected p ≤ 0.005) but with no difference in CMRa. Conclusion Regional brain energy substrate hypometabolism in mild AD dementia may be specific to impaired glucose uptake and/or utilization. This suggests a potential avenue for compensating brain energy deficit in AD dementia with ketones.

Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans.

Abstract: Prolonged elevation of plasma specific fatty acids may exert differential effects on glucose-stimulated insulin secretion (GSIS), insulin sensitivity and clearance. We examined the effect of oral ingestion, at regular intervals for 24 h, of an emulsion containing either predominantly monounsaturated (MUFA), polyunsaturated (PUFA) or saturated (SFA) fat or water (control) on GSIS, insulin sensitivity and insulin clearance in seven overweight or obese, non-diabetic humans. Four studies were conducted in each individual in random order, 4–6 weeks apart. Twenty-four hours after initiation of oral ingestion, subjects underwent a 2 h, 20 mmol/l hyperglycaemic clamp to assess GSIS, insulin sensitivity and insulin clearance. Following oral ingestion of any of the three fat emulsions over 24 h, plasma NEFAs were elevated by ∼1.5- to 2-fold over the basal level. Ingestion of any of the three fat emulsions resulted in reduction in insulin clearance, and SFA ingestion reduced insulin sensitivity. PUFA ingestion was associated with an absolute reduction in GSIS, whereas insulin secretion failed to compensate for insulin resistance in subjects who ingested SFA. Oral ingestion of fats with differing degrees of saturation resulted in different effects on insulin secretion and action. PUFA ingestion resulted in an absolute reduction in insulin secretion and SFA ingestion induced insulin resistance. Failure of insulin secretion to compensate for insulin resistance implies impaired beta cell function in the SFA study.