scholarly journals Ingested Ketone Ester Leads to a Rapid Rise of Acetyl-CoA and Competes with Glucose Metabolism in the Brain of Non-Fasted Mice

2021 ◽  
Vol 22 (2) ◽  
pp. 524
Author(s):  
Laurent Suissa ◽  
Pavel Kotchetkov ◽  
Jean-Marie Guigonis ◽  
Emilie Doche ◽  
Ophélie Osman ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Neurological Diseases ◽  
Feedback Mechanism ◽  
Strongly Correlated ◽  
Acetyl Coa ◽  
First Time ◽  
The Brain ◽  
Ketone Ester

The role of ketone bodies in the cerebral energy homeostasis of neurological diseases has begun to attract recent attention particularly in acute neurological diseases. In ketogenic therapies, ketosis is achieved by either a ketogenic diet or by the administration of exogenous ketone bodies. The oral ingestion of the ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, is a new method to generate rapid and significant ketosis (i.e., above 6 mmol/L) in humans. KE is hydrolyzed into β-hydroxybutyrate (βHB) and its precursor 1,3-butanediol. Here, we investigate the effect of oral KE administration (3 mg KE/g of body weight) on brain metabolism of non-fasted mice using liquid chromatography in tandem with mass spectrometry. Ketosis (Cmax = 6.83 ± 0.19 mmol/L) was obtained at Tmax = 30 min after oral KE-gavage. We found that βHB uptake into the brain strongly correlated with the plasma βHB concentration and was preferentially distributed in the neocortex. We showed for the first time that oral KE led to an increase of acetyl-CoA and citric cycle intermediates in the brain of non-fasted mice. Furthermore, we found that the increased level of acetyl-CoA inhibited glycolysis by a feedback mechanism and thus competed with glucose under physiological conditions. The brain pharmacodynamics of this oral KE strongly suggest that this agent should be considered for acute neurological diseases.

The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

2019 ◽  
Vol 128 (06/07) ◽  
pp. 388-394
Author(s):  
Helge Müller-Fielitz ◽  
Markus Schwaninger
Keyword(s):  
Energy Homeostasis ◽  
Genetic Manipulation ◽  
Heart Function ◽  
Feedback Regulation ◽  
Target Organs ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis ◽  
Hpt Axis ◽  
The Brain

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

Information-based analysis of the coupling between brain and heart reactions to olfactory stimulation

2021 ◽  
pp. 1-11
Author(s):  
Najmeh Pakniyat ◽  
Mohammad Hossein Babini ◽  
Vladimir V. Kulish ◽  
Hamidreza Namazi
Keyword(s):  
Time Series ◽  
Biomedical Science ◽  
Strongly Correlated ◽  
Eeg Signals ◽  
Ecg Signals ◽  
Olfactory Stimuli ◽  
Electrocardiogram Ecg ◽  
First Time ◽  
Electroencephalogram Eeg ◽  
The Brain

BACKGROUND: Analysis of the heart activity is one of the important areas of research in biomedical science and engineering. For this purpose, scientists analyze the activity of the heart in various conditions. Since the brain controls the heart’s activity, a relationship should exist among their activities. OBJECTIVE: In this research, for the first time the coupling between heart and brain activities was analyzed by information-based analysis. METHODS: Considering Shannon entropy as the indicator of the information of a system, we recorded electroencephalogram (EEG) and electrocardiogram (ECG) signals of 13 participants (7 M, 6 F, 18–22 years old) in different external stimulations (using pineapple, banana, vanilla, and lemon flavors as olfactory stimuli) and evaluated how the information of EEG signals and R-R time series (as heart rate variability (HRV)) are linked. RESULTS: The results indicate that the changes in the information of the R-R time series and EEG signals are strongly correlated (ρ=-0.9566). CONCLUSION: We conclude that heart and brain activities are related.

scholarly journals Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

2016 ◽  
Vol 310 (2) ◽  
pp. E103-E115 ◽  
Author(s):  
Lionel Carneiro ◽  
Sarah Geller ◽  
Xavier Fioramonti ◽  
Audrey Hébert ◽  
Cendrine Repond ◽  
...  
Keyword(s):  
Food Intake ◽  
Ketone Body ◽  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Body Level ◽  
Homeostasis Regulation ◽  
The Impact ◽  
Body Concentration

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

scholarly journals Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

2020 ◽  
Vol 21 (22) ◽  
pp. 8767
Author(s):  
Nicole Jacqueline Jensen ◽  
Helena Zander Wodschow ◽  
Malin Nilsson ◽  
Jørgen Rungby
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Brain Metabolism ◽  
Ketone Bodies ◽  
Current Knowledge ◽  
Ketogenic Diets ◽  
Cognitive Benefits ◽  
The Brain

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

scholarly journals Neural Underpinnings of Obesity: The Role of Oxidative Stress and Inflammation in the Brain

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1018
Author(s):  
Caitlyn A. Mullins ◽  
Ritchel B. Gannaban ◽  
Md Shahjalal Khan ◽  
Harsh Shah ◽  
Md Abu B. Siddik ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Energy Homeostasis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Obesity Prevalence ◽  
Beneficial Effects ◽  
The Brain

Obesity prevalence is increasing at an unprecedented rate throughout the world, and is a strong risk factor for metabolic, cardiovascular, and neurological/neurodegenerative disorders. While low-grade systemic inflammation triggered primarily by adipose tissue dysfunction is closely linked to obesity, inflammation is also observed in the brain or the central nervous system (CNS). Considering that the hypothalamus, a classical homeostatic center, and other higher cortical areas (e.g. prefrontal cortex, dorsal striatum, hippocampus, etc.) also actively participate in regulating energy homeostasis by engaging in inhibitory control, reward calculation, and memory retrieval, understanding the role of CNS oxidative stress and inflammation in obesity and their underlying mechanisms would greatly help develop novel therapeutic interventions to correct obesity and related comorbidities. Here we review accumulating evidence for the association between ER stress and mitochondrial dysfunction, the main culprits responsible for oxidative stress and inflammation in various brain regions, and energy imbalance that leads to the development of obesity. Potential beneficial effects of natural antioxidant and anti-inflammatory compounds on CNS health and obesity are also discussed.

scholarly journals The Antiobesity Effects of Centrally Administered Neuromedin U and Neuromedin S Are Mediated Predominantly by the Neuromedin U Receptor 2 (NMUR2)

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3101-3109 ◽  
Author(s):  
Andrea Peier ◽  
Jennifer Kosinski ◽  
Kimberly Cox-York ◽  
Ying Qian ◽  
Kunal Desai ◽  
...  
Keyword(s):  
Food Intake ◽  
Energy Homeostasis ◽  
Central Administration ◽  
Diet Induced Obesity ◽  
Inhibit Food Intake ◽  
Selective Agonists ◽  
Treatment Of Obesity ◽  
The Brain ◽  
Deficient Mice

Neuromedin U (NMU) and neuromedin S (NMS) are structurally related neuropeptides that have been reported to modulate energy homeostasis. Pharmacological data have shown that NMU and NMS inhibit food intake when administered centrally and that NMU increases energy expenditure. Additionally, NMU-deficient mice develop obesity, whereas transgenic mice overexpressing NMU are lean and hypophagic. Two high-affinity NMU/NMS receptors, NMUR1 and NMUR2, have been identified. NMUR1 is predominantly expressed in the periphery, whereas NMUR2 is predominantly expressed in the brain, suggesting that the effects of centrally administered NMU and NMS are mediated by NMUR2. To evaluate the role of NMUR2 in the regulation of energy homeostasis, we characterized NMUR2-deficient (Nmur2−/−) mice. Nmur2−/− mice exhibited a modest resistance to diet-induced obesity that was at least in part due to reduced food intake. Acute central administration of NMU and NMS reduced food intake in wild-type but not in Nmur2−/− mice. The effects on activity and core temperature induced by centrally administered NMU were also absent in Nmur2−/− mice. Moreover, chronic central administration of NMU and NMS evoked significant reductions in body weight and sustained reductions in food intake in mice. In contrast, Nmur2−/− mice were largely resistant to these effects. Collectively, these data demonstrate that the anorectic and weight-reducing actions of centrally administered NMU and NMS are mediated predominantly by NMUR2, suggesting that NMUR2-selective agonists may be useful for the treatment of obesity.

The role of amylin in the control of energy homeostasis

2010 ◽  
Vol 298 (6) ◽  
pp. R1475-R1484 ◽  
Author(s):  
Thomas A. Lutz
Keyword(s):  
Energy Homeostasis ◽  
Area Postrema ◽  
Body Weight Gain ◽  
Direct Action ◽  
Central Administration ◽  
Experimental Conditions ◽  
Hypothalamic Area ◽  
Chronic Infusion ◽  
The Brain

Amylin is an important player in the control of nutrient fluxes. Amylin reduces eating via a meal size effect by promoting meal-ending satiation. This effect seems to depend on a direct action in the area postrema (AP), which is an area rich in amylin receptors. Subsequent to the activation of AP neurons, the neural signal is conveyed to the forebrain via relays involving the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (lPBN) to the lateral hypothalamic area (LHA) and other hypothalamic nuclei. While the NTS and lPBN seem to be necessary for amylin's eating inhibitory effect, the role of the LHA has not yet been fully investigated. Amylin may also act as an adiposity signal. Plasma levels of amylin are higher in obese individuals, and chronic infusion of amylin into the brain reduces body weight gain and adiposity; chronic infusion of an amylin receptor antagonist into the brain increases body adiposity. Amylin increases energy expenditure in rats; this effect occurs under various experimental conditions after peripheral and central administration. Together, these animal data, but also clinical data in humans, indicate that amylin is a promising candidate for the treatment of obesity; effects are most pronounced when amylin is combined with leptin. Finally, recent findings indicate that amylin acts as a neurotrophic factor in specific brain stem areas. Whether this effect may be relevant under physiological conditions requires further studies.

scholarly journals Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

1974 ◽  
Vol 138 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Neil B. Ruderman ◽  
Peter S. Ross ◽  
Michael Berger ◽  
Michael N. Goodman
Keyword(s):  
Glucose Uptake ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Acetyl Coa ◽  
Total Blood ◽  
Diabetic Ketosis ◽  
Pyruvate Oxidation ◽  
Ketone Body Metabolism ◽  
Arteriovenous Difference ◽  
The Brain

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain 's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood –brain barrier may be the rate-limiting step in their metabolism.

scholarly journals Mutual Relationship between Tau and Central Insulin Signalling: Consequences for AD and Tauopathies?

2018 ◽  
Vol 107 (2) ◽  
pp. 181-195 ◽  
Author(s):  
Maud Gratuze ◽  
Aurélie Joly-Amado ◽  
Didier Vieau ◽  
Luc Buée ◽  
David Blum
Keyword(s):  
Tau Protein ◽  
Energy Homeostasis ◽  
Neurodegenerative Disorder ◽  
Insulin Signalling ◽  
Positive Outcome ◽  
Insulin Resistant ◽  
Increased Risk ◽  
Multiple Levels ◽  
The Brain

Alzheimer disease (AD) is a progressive neurodegenerative disorder mainly characterized by cognitive deficits and neuropathological changes such as Tau lesions and amyloid plaques, but also associated with non-cognitive symptomatology. Metabolic and neuroendocrine abnormalities, such as alterations in body weight, brain insulin impairments, and lower brain glucose metabolism, which often precede clinical diagnosis, have been extensively reported in AD patients. However, the origin of these symptoms and their relation to pathology and cognitive impairments remain misunderstood. Insulin is a hormone involved in the control of energy homeostasis both peripherally and centrally, and insulin-resistant state has been linked to increased risk of dementia. It is now well established that insulin resistance can exacerbate Tau lesions, mainly by disrupting the balance between Tau kinases and phosphatases. On the other hand, the emerging literature indicates that Tau protein can also modulate insulin signalling in the brain, thus creating a detrimental vicious circle. The following review will highlight our current understanding of the role of insulin in the brain and its relation to Tau protein in the context of AD and tauopathies. Considering that insulin signalling is prone to be pharmacologically targeted at multiple levels, it constitutes an appealing approach to improve both insulin brain sensitivity and mitigate brain pathology with expected positive outcome in terms of cognition.

scholarly journals Novel Insight Into the Development and Function of Hypopharyngeal Glands in Honey Bees

2021 ◽  
Vol 11 ◽  
Author(s):  
Saboor Ahmad ◽  
Shahmshad Ahmed Khan ◽  
Khalid Ali Khan ◽  
Jianke Li
Keyword(s):  
Honey Bees ◽  
Future Research ◽  
Factors Affecting ◽  
Hypopharyngeal Glands ◽  
And Function ◽  
First Time ◽  
The Brain ◽  
Insight Into ◽  
Made In

Hypopharyngeal glands (HGs) are the most important organ of hymenopterans which play critical roles for the insect physiology. In honey bees, HGs are paired structures located bilaterally in the head, in front of the brain between compound eyes. Each gland is composed of thousands of secretory units connecting to secretory duct in worker bees. To better understand the recent progress made in understanding the structure and function of these glands, we here review the ontogeny of HGs, and the factors affecting the morphology, physiology, and molecular basis of the functionality of the glands. We also review the morphogenesis of HGs in the pupal and adult stages, and the secretory role of the glands across the ages for the first time. Furthermore, recent transcriptome, proteome, and phosphoproteome analyses have elucidated the potential mechanisms driving the HGs development and functionality. This adds a comprehensive novel knowledge of the development and physiology of HGs in honey bees over time, which may be helpful for future research investigations.

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