Mitochondrial Dynamics in the Brain Are Associated With Feeding, Glucose Homeostasis, and Whole-Body Metabolism

Haigh, Jessica L; New, Lauryn E; Filippi, B

doi:10.3389/fendo.2020.580879

Cited by 19 publications

(12 citation statements)

References 202 publications

(316 reference statements)

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“…Besides, NPY is a known regulator of feeding and energy metabolism by affecting mitochondria that, in turn, act as energy sensors in AgRP/NPY hypothalamic neurons. This stimulates appetite and increases energy oxidative metabolism (Billington & Levine, 1992;Haigh et al, 2020;Su et al, 2016). Therefore, NPY can ultimately modulate the activity of key mitochondrial enzymes involved in cellular respiration and oxidative metabolism like CCO, measured here.…”

Section: Introductionmentioning

confidence: 81%

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Méndez-Couz

González-Pardo

Árias

et al. 2021

Preprint

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IntroductionThe neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y2 receptor (Y2R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y2R remain unclear.MethodsHere, we examined the involvement of the hippocampal NPY Y2R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions.ResultsThe acute blockade of NPY Y2R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies.ConclusionsThese findings suggest that the NPY hippocampal system, through its Y2R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y2R modulation of long-term potentiation and long-term depression.HighlightsUnder hippocampal Y2R antagonism, place preference memory retrieval is enhancedSpatial retrieval enhancement under Y2R blockade is correlated with changes in regional brain energy metabolismEnhanced retrieval associated CCO activity increases in the dorsal DG, while decreasing in the ventral CA1, IL cortex and mammillary bodiesY2R exert control over patterns of brain activation that are relevant for spatial memory expression

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Section: Introductionmentioning

confidence: 81%

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Méndez-Couz

González-Pardo

Árias

et al. 2021

Preprint

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“…This occurs mainly in the brain and in particular in the hypothalamus; however, it also involves sensors at the cellular and organelle level in the liver, pancreas, muscles, adipose tissues, and gut [ 30 , 31 ]. Mitochondrial dynamics also play an important role in energy homeostasis due to their ATP producing capacity [ 32 ].…”

Section: Metabolic Inflexibilitymentioning

confidence: 99%

The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation

Virmani¹,

Cirulli²

2022

IJMS

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Mitochondria control cellular fate by various mechanisms and are key drivers of cellular metabolism. Although the main function of mitochondria is energy production, they are also involved in cellular detoxification, cellular stabilization, as well as control of ketogenesis and glucogenesis. Conditions like neurodegenerative disease, insulin resistance, endocrine imbalances, liver and kidney disease are intimately linked to metabolic disorders or inflexibility and to mitochondrial dysfunction. Mitochondrial dysfunction due to a relative lack of micronutrients and substrates is implicated in the development of many chronic diseases. L-carnitine is one of the key nutrients for proper mitochondrial function and is notable for its role in fatty acid oxidation. L-carnitine also plays a major part in protecting cellular membranes, preventing fatty acid accumulation, modulating ketogenesis and glucogenesis and in the elimination of toxic metabolites. L-carnitine deficiency has been observed in many diseases including organic acidurias, inborn errors of metabolism, endocrine imbalances, liver and kidney disease. The protective effects of micronutrients targeting mitochondria hold considerable promise for the management of age and metabolic related diseases. Preventing nutrient deficiencies like L-carnitine can be beneficial in maintaining metabolic flexibility via the optimization of mitochondrial function. This paper reviews the critical role of L-carnitine in mitochondrial function, metabolic flexibility and in other pathophysiological cellular mechanisms.

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“…Healthy and fully functional mitochondria are maintained by unique equilibrium among the processes of mitochondrial biogenesis, removal of damaged mitochondria by mitophagy, and mitochondrial dynamics, which are regulated by mitofusins Mfn1, Mfn2, Drp1, and OPA1. Mitochondrial dynamics in the brain are associated with feeding, glucose homeostasis, and whole-body metabolism, and disorders of mitochondrial fission–fusion proteins are observed in obesity, DM, and neuroinflammation [ 127 ]. Mfn1 has recently emerged as a nutrient sensor in POMC neurons that influences whole-body glucose metabolism as it plays a key role in the central control of insulin release [ 128 ].…”

Section: Mitochondrial Proteostasis In the Diabetic Brainmentioning

confidence: 99%

Toward the Decipherment of Molecular Interactions in the Diabetic Brain

Chomová

2022

Biomedicines

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Diabetes mellitus (DM) has been associated with cognitive complications in the brain resulting from acute and chronic metabolic disturbances happening peripherally and centrally. Numerous studies have reported on the morphological, electrophysiological, biochemical, and cognitive changes in the brains of diabetic individuals. The detailed pathophysiological mechanisms implicated in the development of the diabetic cognitive phenotype remain unclear due to intricate molecular changes evolving over time and space. This review provides an insight into recent advances in understanding molecular events in the diabetic brain, focusing on cerebral glucose and insulin uptake, insulin action in the brain, and the role of the brain in the regulation of glucose homeostasis. Fully competent mitochondria are essential for energy metabolism and proper brain function; hence, the potential contribution of mitochondria to the DM-induced impairment of the brain is also discussed.

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Mitochondrial Dynamics in the Brain Are Associated With Feeding, Glucose Homeostasis, and Whole-Body Metabolism

Cited by 19 publications

References 202 publications

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation

Toward the Decipherment of Molecular Interactions in the Diabetic Brain

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Mitochondrial Dynamics in the Brain Are Associated With Feeding, Glucose Homeostasis, and Whole-Body Metabolism

Cited by 19 publications

References 202 publications

Hippocampal Neuropeptide Y2receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal Neuropeptide Y2receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation

Toward the Decipherment of Molecular Interactions in the Diabetic Brain

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Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism

Hippocampal Neuropeptide Y₂receptor blockade improves spatial memory retrieval and modulates limbic brain metabolism