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Metabolites
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Brain Substrate Metabolism in Health and Disease
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Brain Substrate Metabolism in Health and Disease

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Nutrition and Metabolism".

Deadline for manuscript submissions: closed (15 August 2023) | Viewed by 7037

Special Issue Editor

Dr. Eleni Rebelos

E-Mail Website
Guest Editor
Turku PET Centre, Turku, Finland
Interests: brain; glucose metabolism; neuroimaging; obesity; insulin resistance; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent decades, we have been facing a global epidemic of obesity, with its prevalence having tripled in the last four decades. Currently, more than 1.9 billion people are overweight, and over 650 million people are obese. Several research lines have shown that in the context of obesity and insulin resistance, brain glucose and free fatty acid uptake are altered. Some reports have also suggested that an altered brain metabolism in the context of systemic insulin resistance may contribute to further worsening of whole-body homeostasis.

On the other hand, brain glucose metabolism alterations are also well described in the context of mild cognitive impairment and Alzheimer’s disease, while it seems that metabolic and neurologic disorders may share common pathophysiologic pathways. Neuroimaging (PET, MRI, fMRI, MRS, MEG) provides unique opportunities to study the human brain non-invasively. This Special Issue welcomes studies performed in humans assessing brain substrate metabolism (assessed with neuroimaging) in the context of metabolic and neurologic disorders. Preclinical research which may shed more light in the brain findings into these disease is also welcome.

Dr. Eleni Rebelos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • obesity
  • insulin resistance
  • neuroimaging
  • positron emission tomography
  • Alzheimer’s disease

Published Papers (4 papers)

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Editorial

Jump to: Research, Review

3 pages, 179 KiB  
Editorial
Insulin Resistance and the Brain–Novel Insights Combining Metabolic Research and Neuroscience
by Laura Ekblad and Eleni Rebelos
Metabolites 2022, 12(9), 780; https://doi.org/10.3390/metabo12090780 - 24 Aug 2022
Viewed by 928
Abstract
In the last decades, we have been facing an epidemic of obesity and type 2 diabetes (T2D) [...] Full article
(This article belongs to the Special Issue Brain Substrate Metabolism in Health and Disease)

Research

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12 pages, 818 KiB  
Article
Metabolic Covariance Connectivity of Posterior Cingulate Cortex Associated with Depression Symptomatology Level in Healthy Young Adults
by Zhixin Wang, Chris Baeken and Guo-Rong Wu
Metabolites 2023, 13(8), 920; https://doi.org/10.3390/metabo13080920 - 06 Aug 2023
Viewed by 929
Abstract
Early detection in the development of a Major Depressive Disorder (MDD) could guide earlier clinical interventions. Although MDD can begin at a younger age, most people have their first episode in young adulthood. The underlying pathophysiological mechanisms relating to such an increased risk [...] Read more.
Early detection in the development of a Major Depressive Disorder (MDD) could guide earlier clinical interventions. Although MDD can begin at a younger age, most people have their first episode in young adulthood. The underlying pathophysiological mechanisms relating to such an increased risk are not clear. The posterior cingulate cortex (PCC), exhibiting high levels of brain connectivity and metabolic activity, plays a pivotal role in the pathological mechanism underlying MDD. In the current study, we used the (F-18) fluorodeoxyglucose (FDG) positron emission tomography (PET) to measure metabolic covariance connectivity of the PCC and investigated its association with depression symptomatology evaluated by the Centre for Epidemiological Studies Depression Inventory—Revised (CESD-R) among 27 healthy individuals aged between 18 and 23 years. A significant negative correlation has been observed between CESD-R scale scores and the PCC metabolic connectivity with the anterior cingulate, medial prefrontal cortex, inferior and middle frontal gyrus, as well as the insula. Overall, our findings suggest that the neural correlates of depressive symptomatology in healthy young adults without a formal diagnosis involve the metabolic connectivity of the PCC. Our findings may have potential implications for early identification and intervention in people at risk of developing depression. Full article
(This article belongs to the Special Issue Brain Substrate Metabolism in Health and Disease)
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12 pages, 8817 KiB  
Article
Thermogenic Capacity of Human Supraclavicular Brown Fat and Cold-Stimulated Brain Glucose Metabolism
by Mueez U-Din, Eleni Rebelos, Teemu Saari, Tarja Niemi, Katharina Kuellmer, Olli Eskola, Tobias Fromme, Johan Rajander, Markku Taittonen, Martin Klingenspor, Pirjo Nuutila, Lauri Nummenmaa and Kirsi A. Virtanen
Metabolites 2023, 13(3), 387; https://doi.org/10.3390/metabo13030387 - 05 Mar 2023
Cited by 1 | Viewed by 1959
Abstract
Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation [...] Read more.
Human brain metabolism is susceptible to temperature changes. It has been suggested that the supraclavicular brown adipose tissue (BAT) protects the brain from these fluctuations by regulating heat production through the presence of uncoupling protein 1 (UCP-1). It remains unsolved whether inter-individual variation in the expression of UCP-1, which represents the thermogenic capacity of the supraclavicular BAT, is linked with brain metabolism during cold stress. Ten healthy human participants underwent 18F-FDG PET scanning of the brain under cold stimulus to determine brain glucose uptake (BGU). On a separate day, an excision biopsy of the supraclavicular fat—the fat proximal to the carotid arteries supplying the brain with warm blood—was performed to determine the mRNA expression of the thermogenic protein UCP-1. Expression of UCP-1 in supraclavicular BAT was directly related to the whole brain glucose uptake rate determined under cold stimulation (rho = 0.71, p = 0.03). In sub-compartmental brain analysis, UCP-1 expression in supraclavicular BAT was directly related to cold-stimulated glucose uptake rates in the hypothalamus, medulla, midbrain, limbic system, frontal lobe, occipital lobe, and parietal lobe (all rho ≥ 0.67, p < 0.05). These relationships were independent of body mass index and age. When analysing gene expressions of BAT secretome, we found a positive correlation between cold-stimulated BGU and DIO2. These findings provide evidence of functional links between brain metabolism under cold stimulation and UCP-1 and DIO2 expressions in BAT in humans. More research is needed to evaluate the importance of these findings in clinical outcomes, for instance, in examining the supporting role of BAT in cognitive functions under cold stress. Full article
(This article belongs to the Special Issue Brain Substrate Metabolism in Health and Disease)
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Review

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27 pages, 1696 KiB  
Review
Multinuclear Magnetic Resonance Spectroscopy at Ultra-High-Field: Assessing Human Cerebral Metabolism in Healthy and Diseased States
by Pandichelvam Veeraiah and Jacobus F. A. Jansen
Metabolites 2023, 13(4), 577; https://doi.org/10.3390/metabo13040577 - 19 Apr 2023
Cited by 2 | Viewed by 1874
Abstract
The brain is a highly energetic organ. Although the brain can consume metabolic substrates, such as lactate, glycogen, and ketone bodies, the energy metabolism in a healthy adult brain mainly relies on glucose provided via blood. The cerebral metabolism of glucose produces energy [...] Read more.
The brain is a highly energetic organ. Although the brain can consume metabolic substrates, such as lactate, glycogen, and ketone bodies, the energy metabolism in a healthy adult brain mainly relies on glucose provided via blood. The cerebral metabolism of glucose produces energy and a wide variety of intermediate metabolites. Since cerebral metabolic alterations have been repeatedly implicated in several brain disorders, understanding changes in metabolite levels and corresponding cell-specific neurotransmitter fluxes through different substrate utilization may highlight the underlying mechanisms that can be exploited to diagnose or treat various brain disorders. Magnetic resonance spectroscopy (MRS) is a noninvasive tool to measure tissue metabolism in vivo. 1H-MRS is widely applied in research at clinical field strengths (≤3T) to measure mostly high abundant metabolites. In addition, X-nuclei MRS including, 13C, 2H, 17O, and 31P, are also very promising. Exploiting the higher sensitivity at ultra-high-field (>4T; UHF) strengths enables obtaining unique insights into different aspects of the substrate metabolism towards measuring cell-specific metabolic fluxes in vivo. This review provides an overview about the potential role of multinuclear MRS (1H, 13C, 2H, 17O, and 31P) at UHF to assess the cerebral metabolism and the metabolic insights obtained by applying these techniques in both healthy and diseased states. Full article
(This article belongs to the Special Issue Brain Substrate Metabolism in Health and Disease)
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