AMPK in the Ventromedial Nucleus of the Hypothalamus: A Key Regulator for Thermogenesis

Liu, Hailan; Xu, Yong; Hu, Fang

doi:10.3389/fendo.2020.578830

Cited by 15 publications

(16 citation statements)

References 167 publications

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“…Increasing evidence supports a relevant role of AMPK in the physiopathology of the central nervous system (Camici et al, 2020). The roles of AMPK in brain and its cross-talk with many hormones in the hypothalamus to mediate their anorexigenic and orexigenic effects as well as thermogenic influences have been thoroughly reviewed (Huynh et al, 2016;Rosso et al, 2016;Peixoto et al, 2017;Liu et al, 2020).…”

Section: Amp-activated Protein Kinasementioning

confidence: 99%

“…In fact, in these conditions, both the cytosolic 5'-nucleotidase II (NT5C2) and AMP deaminase (AMPD) are allosterically activated by ATP (Figure 2) (Ashby and Holmsen, 1983;Tozzi et al, 2013), therefore AMP is deaminated by AMPD into IMP, which is dephosphorylated into inosine by NT5C2. Conversely, at low energy charge, the accumulation of AMP inside the cell, leads to the activation of a specific AMP-activated protein kinase (AMPK), the main regulator of cellular energy homeostasis (Hardie et al, 2012;Rosso et al, 2016;Peixoto et al, 2017;Liu et al, 2020) (Figure 2). The dephosphorylation of AMP by a high FIGURE 1 | Extra-and intracellular adenosine production.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.

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Section: Amp-activated Protein Kinasementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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“…The hypothalamus integrates sensory input from the internal and external environments and secretes regulatory neuropeptides and monoamines, which continually fine-tune physiological functions and maintain body homeostasis 17,18 . Several studies have demonstrated the thermoregulatory roles of hypothalamus in homeotherms 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Oxytocin Signaling Regulates the Homeostatic Response to Cold Stress in Poikilothermic Vertebrates

Segev

Krispin

Olthof

et al. 2021

Preprint

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When exposed to low temperature, homeothermic vertebrates maintain internal body temperature by activating thermogenesis and by altered metabolism, synchronized by neuroendocrine responses. Although such physiological responses also occur in poikilothermic vertebrates, the prevailing notion is that their reactions are passive. Here, we explored molecular hypothalamic and physiological responses to cold stress in the tropical poikilotherm Nile tilapia (Oreochromis niloticus). We show that cold exposed tilapia exhibit complex homeostatic responses, including increased hypothalamic oxytocin, plasma glucose and cortisol concomitant with reduced plasma lactate and metabolic rate. Pharmacological or genetic blockage of oxytocin signaling further affected metabolic rate in two cold-exposed poikilothermic models. This indicates that oxytocin, a known thermoregulator in homeotherms, actively regulates temperature-related homeostasis in poikilotherms. Overall, our findings show that the brain of poikilotherms actively responds to cold temperature by regulating metabolic physiology. Moreover, we identify oxytocin signaling as an adaptive and evolutionarily conserved metabolic regulator of temperature-related homeostasis.

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“…1 ). In addition to thermogenesis, appetitive, social and sexual behaviours, the VMH has also been well-documented in the regulation of body weight and glucose homeostasis [ 2 , 14 , 64 , 65 ]. Hetherington and Ranson have demonstrated that lesion of the VMH results into a massive obesity and marked adiposity in rats, and another study revealed that VMH lesions blunt CRR to insulin-induced hypoglycemia [ 13 , 66 ].…”

Section: Glucose-sensing Neurons In the Brainmentioning

confidence: 99%

The ventromedial hypothalamic nucleus: watchdog of whole-body glucose homeostasis

Fukuda

Tong

et al. 2022

Cell Biosci

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The brain, particularly the ventromedial hypothalamic nucleus (VMH), has been long known for its involvement in glucose sensing and whole-body glucose homeostasis. However, it is still not fully understood how the brain detects and responds to the changes in the circulating glucose levels, as well as brain-body coordinated control of glucose homeostasis. In this review, we address the growing evidence implicating the brain in glucose homeostasis, especially in the contexts of hypoglycemia and diabetes. In addition to neurons, we emphasize the potential roles played by non-neuronal cells, as well as extracellular matrix in the hypothalamus in whole-body glucose homeostasis. Further, we review the ionic mechanisms by which glucose-sensing neurons sense fluctuations of ambient glucose levels. We also introduce the significant implications of heterogeneous neurons in the VMH upon glucose sensing and whole-body glucose homeostasis, in which sex difference is also addressed. Meanwhile, research gaps have also been identified, which necessities further mechanistic studies in future.

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AMPK in the Ventromedial Nucleus of the Hypothalamus: A Key Regulator for Thermogenesis

Cited by 15 publications

References 167 publications

Metabolic Aspects of Adenosine Functions in the Brain

Metabolic Aspects of Adenosine Functions in the Brain

Oxytocin Signaling Regulates the Homeostatic Response to Cold Stress in Poikilothermic Vertebrates

The ventromedial hypothalamic nucleus: watchdog of whole-body glucose homeostasis

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