Central Dicer-miR-103/107 controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis

Croizier, Sophie; Park, Soyoung; Maillard, Julien; Bouret, Sébastien G.

doi:10.7554/elife.40429

Cited by 33 publications

(29 citation statements)

References 49 publications

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“…Interestingly, most POMC and AgRP neurons express Dicer . Deletion of Dicer in POMC neurons causes post-natal neurodegeneration resulting in increased appetite, obesity and T2D ( Figure 3 ) [141–143]. In agreement with these observations, brain- and ARC-specific deletion of Dicer causes similar metabolic alterations [144, 145].…”

Section: Epigenetics Of Energy Balance Control In the Hypothalamussupporting

confidence: 59%

The role of epigenetics in hypothalamic energy balance control: implications for obesity

Obri¹,

Claret²

2019

CST

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Despite enormous social and scientific efforts, obesity rates continue to increase worldwide. While genetic factors contribute to obesity development, genetics alone cannot explain the current epidemic. Obesity is essentially the consequence of complex genetic-environmental interactions. Evidence suggests that contemporary lifestyles trigger epigenetic changes, which can dysregulate energy balance and thus contribute to obesity. The hypothalamus plays a pivotal role in the regulation of body weight, through a sophisticated network of neuronal systems. Alterations in the activity of these neuronal pathways have been implicated in the pathophysiology of obesity. Here, we review the current knowledge on the central control of energy balance with a focus on recent studies linking epigenetic mechanisms in the hypothalamus to the development of obesity and metabolic disorders.

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Section: Epigenetics Of Energy Balance Control In the Hypothalamussupporting

confidence: 59%

The role of epigenetics in hypothalamic energy balance control: implications for obesity

Obri¹,

Claret²

2019

CST

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“…In addition, since melanocortin signaling and Kiss1 neurons have been shown to interplay for the regulation of puberty (Manfredi-Lozano et al 2016), a putative role of kisspeptins in such a novel circuitry cannot be discarded. In the same vein, whether miRNA regulatory pathways, with relevant roles in the development of feeding-controlling circuits in the ARC (Croizier et al 2018) and the functional maturation of GnRH neurons (Messina et al 2016), may participate in the metabolic control of puberty is currently being investigated in our laboratory.…”

Section: Metabolic Control Of Puberty In Mammals: Key Hormonal and Nementioning

confidence: 99%

Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition

Vázquez

Velasco

Tena‐Sempere

2019

Journal of Endocrinology

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Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing the reproductive axis. The timing of puberty is genetically determined; yet, puberty is also sensitive to numerous internal and external cues, among which metabolic/nutritional signals are especially prominent. Compelling epidemiological evidence suggests that alterations of the age of puberty are becoming more frequent; the underlying mechanisms remain largely unknown, but the escalating prevalence of obesity and other metabolic/feeding disorders is possibly a major contributing factor. This phenomenon may have clinical implications, since alterations in pubertal timing have been associated to adverse health outcomes, including higher risk of earlier all-cause mortality. This urges for a better understanding of the neurohormonal basis of normal puberty and its deviations. Compelling evidence has recently documented the master role of hypothalamic neurons producing kisspeptins, encoded by Kiss1, in the neuroendocrine pathways controlling puberty. Kiss1 neurons seemingly participate in transmitting the regulatory actions of metabolic cues on pubertal maturation. Key cellular metabolic sensors, as the mammalian target of rapamycin (mTOR), AMP-activated protein kinase (AMPK) and the fuel-sensing deacetylase, SIRT1, have been recently shown to participate also in the metabolic modulation of puberty. Recently, we have documented that AMPK and SIRT1 operate as major molecular effectors for the metabolic control of Kiss1 neurons and, thereby, puberty onset. Alterations of these molecular pathways may contribute to the perturbation of pubertal timing linked to conditions of metabolic stress in humans, such as subnutrition or obesity and might become druggable targets for better management of pubertal disorders.

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“…Specifically, Dicer KO in hypothalamic POMC neurons induces obesity and hyperglycemia caused by hyperphagia in combination with declined energy expenditure [ 10 , 11 ]. Moreover, aging witnesses a decline in Dicer level in the hypothalamus, leading to differentiation of Pomc -expressing progenitors into AgRP/NPY phenotype and subsequent metabolic dysregulation, which is possibly mediated by mir-107/103 [ 21 ]. Thus, it is assumable that, through specific miRNAs like mir-103 in POMC neurons, Dicer positively promotes catabolic metabolism.…”

Section: Regulation Of Catabolism By Dicer In the Central Nervous mentioning

confidence: 99%

Function of Dicer with regard to Energy Homeostasis Regulation, Structural Modification, and Cellular Distribution

Tong

Han

et al. 2020

International Journal of Endocrinology

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As a type III ribonuclease (RNase III) specifically cleaving double-stranded RNA substrates into short fragments, Dicer is indispensable in a range of physi/pathologic processes, e.g., nutrient deprivation, hypoxia, or DNA damage. Therefore, much interest has been paid to the research of this protein as well as its products like microRNAs (miRNAs). The close relationship between Dicer levels and fluctuations of nutrient availability suggests that the protein participates in the regulation of systemic energy homeostasis. Through miRNAs, Dicer regulates the hypothalamic melanocortin-4 system and central autophagy promoting energy expenditure. Moreover, by influencing canonical energy sensors like adenosine monophosphate-activated protein kinase (AMPK) or mammalian target of rapamycin (mTOR), Dicer favors catabolism in the periphery. Taken together, Dicer might be targeted in the control of energy dysregulation. However, factors affecting its RNase activity should be noted. Firstly, modulation of structural integrity affects its role as a ribonuclease. Secondly, although previously known as a cytosolic endoribonuclease, evidence suggests Dicer can relocalize into the nucleus where it could also produce small RNAs. In this review, we probe into involvement of Dicer in energy homeostasis as well as its structural integrity or cellular distribution which affects its ability to produce miRNAs, in the hope of providing novel insights into its mechanism of action for future application.

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Central Dicer-miR-103/107 controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis

Cited by 33 publications

References 49 publications

The role of epigenetics in hypothalamic energy balance control: implications for obesity

The role of epigenetics in hypothalamic energy balance control: implications for obesity

Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition

Function of Dicer with regard to Energy Homeostasis Regulation, Structural Modification, and Cellular Distribution

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