Exercise in a Pill: The Latest on Exercise-Mimetics

Guerrieri, Davide; Moon, Hyo Youl; Praag, Henriette van

doi:10.3233/bpl-160043

Cited by 64 publications

(75 citation statements)

References 145 publications

(126 reference statements)

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“…Future studies are urgently needed that combine animal and human exercise research with extensive test batteries to foster our understanding on how exercise can induce neuroplasticity. Identifying the underlying molecular mechanisms will help to design (i) more tailored exercise interventions [149] and (ii) pharmacological agents that can mimic the effects of physical exercise [150].…”

Section: Discussionmentioning

confidence: 99%

Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?

Müller

Duderstadt

Leßmann

et al. 2020

JCM

115

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Accumulating evidence from animal and human studies supports the notion that physical exercise can enhance neuroplasticity and thus reduce the risk of several neurodegenerative diseases (e.g., dementia). However, the underlying neurobiological mechanisms of exercise induced neuroplasticity are still largely unknown. One potential mediator of exercise effects is the neurotrophin BDNF, which enhances neuroplasticity via different pathways (e.g., synaptogenesis, neurogenesis, long-term potentiation). Current research has shown that (i) increased peripheral lactate levels (following high intensity exercise) are associated with increased peripheral BDNF levels, (ii) lactate infusion at rest can increase peripheral and central BDNF levels and (iii) lactate plays a very complex role in the brain’s metabolism. In this review, we summarize the role and relationship of lactate and BDNF in exercise induced neuroplasticity.

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Section: Discussionmentioning

confidence: 99%

Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?

Müller

Duderstadt

Leßmann

et al. 2020

JCM

115

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“…The drug AICAR is mainly known to the public for its potential use in doping, and it has been placed on the list of illegal substances by the World Anti‐Doping Agency. The reason it can be used for doping is that it is an exercise mimetic . After phosphorylation within the cell, AICAR becomes 5‐amino‐4‐imidazolecarboxamide ribose‐monophosphate (ZMP), an analog of AMP.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential drugs for treatment of hepatic lipidosis in cats using an in vitro feline liver organoid system

Haaker

Kruitwagen

Vaandrager

et al. 2019

Veterinary Internal Medicne

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Background: Hepatic lipidosis is increasing in incidence in the Western world, with cats being particularly sensitive. When cats stop eating and start utilizing their fat reserves, free fatty acids (FFAs) increase in blood, causing an accumulation of triacylglycerol (TAG) in the liver.Objective: Identifying potential new drugs that can be used to treat hepatic lipidosis in cats using a feline hepatic organoid system. Animals: Liver organoids obtained from 6 cats.Methods: Eight different drugs were tested, and the 2 most promising were further studied using a quantitative TAG assay, lipid droplet staining, and qPCR. Results: Both T863 (a diacylglycerol O-acyltransferase 1 [DGAT1] inhibitor) and 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR; an adenosine monophosphate kinase activator) decreased TAG accumulation by 55% (P < .0001) and 46% (P = .0003), respectively. Gene expression of perilipin 2 (PLIN2) increased upon the addition of FFAs to the medium and decreased upon treatment with AICAR but not significantly after treatment with T863.Conclusions and Clinical Importance: Two potential drugs useful in the treatment of hepatic lipidosis in cats were identified. The drug T863 inhibits DGAT1, indicating that DGAT1 is the primary enzyme responsible for TAG synthesis from external fatty acids in cat organoids. The drug AICAR may act as a lipid-lowering compound via decreasing PLIN2 mRNA. Liver organoids can be used as an in vitro tool for drug testing in a species-specific system and provide the basis for further clinical testing of drugs to treat steatosis. K E Y W O R D SAICAR, diacylglycerol O-acyltransferase 1 inhibitor, hepatic organoids, perilipin 2, steatosis Abbreviations: AICAR, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside; AMPK, adenosine monophosphate-activated protein kinase; AMPKK, AMPK kinase; CYP3A132, cytochrome 3A132; DAG, diacylglycerol; DGAT, diacylglycerol O-acyltransferase; FFA, free fatty acid; HMBS, hydroxymethylbilane synthase; HPRT-1, hypoxanthine phosphoribosyltransferase 1; LGR5, leucine-rich repeat-containing G protein-coupled receptor 5; NAFLD, non-alcoholic fatty liver disease; PLIN2, perilipin 2; RPS5, ribosomal protein S5; TAG, triacylglycerol; TTR, transthyretin; YWHAZ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta; ZMP, 5-amino-4-imidazolecarboxamide ribose-monophosphate.Maya W. Haaker and Hedwig S. Kruitwagen contributed equally to this work.

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“…An important “master regulator” of muscle physiology is AMP-activated protein kinase (AMPK) (Hardie 2011). Activation of AMPK with an agonist, AICAR, decreased fat mass, increased oxygen consumption, and increased running endurance in sedentary mice by reprogramming muscle fibers to a type I phenotype in a PPARδ-dependent manner (Narkar et al 2008; Guerrieri et al 2017). To determine whether the effects on endurance extended to brain function, we treated mice with AICAR and spatial memory was tested (Kobilo et al 2011b, 2014).…”

Section: Peripheral Organs and Brain Functionmentioning

confidence: 99%

On the Run for Hippocampal Plasticity

Cooper

Moon

Praag

2017

Cold Spring Harb Perspect Med

Self Cite

119

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Accumulating research in rodents and humans indicates that exercise benefits brain function and may prevent or delay onset of neurodegenerative conditions. In particular, exercise modifies the structure and function of the hippocampus, a brain area important for learning and memory. This review addresses the central and peripheral mechanisms underlying the beneficial effects of exercise on the hippocampus. We focus on running-induced changes in adult hippocampal neurogenesis, neural circuitry, neurotrophins, synaptic plasticity, neurotransmitters, and vasculature. The role of peripheral factors in hippocampal plasticity is also highlighted. We discuss recent evidence that systemic factors released from peripheral organs such as muscle (myokines), liver (hepatokines), and adipose tissue (adipokines) during exercise contribute to hippocampal neurotrophin and neurogenesis levels, and memory function. A comprehensive understanding of the body–brain axis is needed to elucidate how exercise improves hippocampal plasticity and cognition.

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Exercise in a Pill: The Latest on Exercise-Mimetics

Cited by 64 publications

References 145 publications

Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?

Lactate and BDNF: Key Mediators of Exercise Induced Neuroplasticity?

Identification of potential drugs for treatment of hepatic lipidosis in cats using an in vitro feline liver organoid system

On the Run for Hippocampal Plasticity

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