Brain insulin sensitivity is linked to body fat distribution—the positron emission tomography perspective

Rebelos, Eleni; Nummenmaa, Lauri; Dadson, Prince; Latva‐Rasku, Aino; Nuutila, Pirjo

doi:10.1007/s00259-020-05064-7

Cited by 9 publications

(13 citation statements)

References 11 publications

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“…Since there is no feasible method to evaluate brain insulin resistance in humans at tissue level, addressing brain metabolism in the living human brain and in a relatively minimally invasive manner relies on neuroimaging. Since neuroimaging studies are difficult and expensive to perform, and only few specialized neuroimaging centers exist around the globe, there is a thus far unmet need to translate the findings of one neuroimaging approach to the other [12]. For this reason, in the present study, we addressed whether in our [ 18 F]-FDG/PET dataset, carrying the rs17782313-C allele could have affected the central findings, in parallel to the findings of Tschritter et al As in the aforementioned study, also in our dataset presence of the obesity risk allele rs17782313-C did not lead to differences in BMI or insulin sensitivity (M value).…”

Section: Discussionmentioning

confidence: 99%

“…Our group on the contrary, has consistently found increased brain glucose uptake (BGU) during conditions of euglycemic insulin clamp in obese/insulin resistant individuals [10], and also in individuals carrying a loss-of-function variant of the gene AKT2 that increases the risk for type 2 diabetes [11]. In a recent report, we have tried to underline the problem of lack of a ground truth definition of central insulin resistance, and the need for multiple measurements with different neuroimaging modalities in the same subjects so that the findings of neuroimaging studies can be better understood [12]. In this study, based on the previous findings of Tschritter and colleagues, we wished to evaluate whether in our dataset of brain insulin clamp [ 18 F]FDG/PET studies, presence of the rs17782313-C allele would associate with increased BGU during insulin stimulation.…”

Section: Introductionmentioning

confidence: 99%

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The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

Rebelos

Honka

Ekblad

et al. 2021

JCM

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The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the MC4R gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

Rebelos

Honka

Ekblad

et al. 2021

JCM

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“…Most studies trying to address whether there is central IR in the context of systemic IR have used neuroimaging methods, such as PET, functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG). Therefore, the definition of brain IR has varied depending on the implemented method: i.e., a blunted cerebrocortical insulin effect in obese individuals when compared to lean when MEG is applied [ 106 ]; decreased intranasal insulin-induced suppression of hypothalamic blood flow in fMRI [ 15 ]; or an insulin-induced increase in brain glucose uptake (BGU) in [ 18 F]-FDG-PET studies [ 13 , 99 ]. However, since multiple measures with different neuroimaging modalities are typically not used within a single study, the integration of these results is difficult.…”

Section: Attempts To Define Central Insulin Resistancementioning

confidence: 99%

“…However, many open questions remain, in particular considering the possible relationship between systemic IR and brain glucose uptake (BGU), measured with fluorine-labeled fluorodeoxyglucose positron emission tomography [ 18 F]-FDG-PET, and how these alterations in BGU might affect or reflect neurodegeneration and the neuropathological changes of AD. At present, the association between IR and cerebral changes is being studied both by groups focusing on metabolic disorders in middle-aged or young subjects [ 12 , 13 , 14 , 15 ] and by groups specialized in dementia research [ 6 , 16 , 17 , 18 , 19 , 20 ]. In this review, we aim to combine results from both lines of research in an attempt to clarify the latest results evaluating the association between peripheral IR and brain glucose uptake, with a special emphasis on the interpretation of the differences in findings from [ 18 F]-FDG-PET scans performed in the fasting state and during an insulin-stimulated state, i.e., the hyperinsulinemic euglycemic clamp.…”

Section: Introductionmentioning

confidence: 99%

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Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

Rebelos

Rinne

Nuutila

2021

JCM

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Imaging brain glucose metabolism with fluorine-labelled fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) has long been utilized to aid the diagnosis of memory disorders, in particular in differentiating Alzheimer’s disease (AD) from other neurological conditions causing cognitive decline. The interest for studying brain glucose metabolism in the context of metabolic disorders has arisen more recently. Obesity and type 2 diabetes—two diseases characterized by systemic insulin resistance—are associated with an increased risk for AD. Along with the well-defined patterns of fasting [18F]-FDG-PET changes that occur in AD, recent evidence has shown alterations in fasting and insulin-stimulated brain glucose metabolism also in obesity and systemic insulin resistance. Thus, it is important to clarify whether changes in brain glucose metabolism are just an epiphenomenon of the pathophysiology of the metabolic and neurologic disorders, or a crucial determinant of their pathophysiologic cascade. In this review, we discuss the current knowledge regarding alterations in brain glucose metabolism, studied with [18F]-FDG-PET from metabolic disorders to AD, with a special focus on how manipulation of insulin levels affects brain glucose metabolism in health and in systemic insulin resistance. A better understanding of alterations in brain glucose metabolism in health, obesity, and neurodegeneration, and the relationships between insulin resistance and central nervous system glucose metabolism may be an important step for the battle against metabolic and cognitive disorders.

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The insulin resistant brain: impact on whole-body metabolism and body fat distribution

Heni

2024

Diabetologia

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Insulin exerts its actions not only on peripheral organs but is also transported into the brain where it performs distinct functions in various brain regions. This review highlights recent advancements in our understanding of insulin’s actions within the brain, with a specific emphasis on investigations in humans. It summarises current knowledge on the transport of insulin into the brain. Subsequently, it showcases robust evidence demonstrating the existence and physiological consequences of brain insulin action, while also introducing the presence of brain insulin resistance in humans. This pathophysiological condition goes along with an impaired acute modulation of peripheral metabolism in response to brain insulin action, particularly in the postprandial state. Furthermore, brain insulin resistance has been associated with long-term adiposity and an unfavourable adipose tissue distribution, thus implicating it in the pathogenesis of subgroups of obesity and (pre)diabetes that are characterised by distinct patterns of body fat distribution. Encouragingly, emerging evidence suggests that brain insulin resistance could represent a treatable entity, thereby opening up novel therapeutic avenues to improve systemic metabolism and enhance brain functions, including cognition. The review closes with an outlook towards prospective research directions aimed at further elucidating the clinical implications of brain insulin resistance. It emphasises the critical need to establish feasible diagnostic measures and effective therapeutic interventions. Graphical Abstract

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Brain insulin sensitivity is linked to body fat distribution—the positron emission tomography perspective

Cited by 9 publications

References 11 publications

The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

Brain Glucose Metabolism in Health, Obesity, and Cognitive Decline—Does Insulin Have Anything to Do with It? A Narrative Review

The insulin resistant brain: impact on whole-body metabolism and body fat distribution

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