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Hypothalamic miRNAs: emerging roles in energy balance control.

Schneeberger M, Gomez-Valadés AG, Ramirez S, Gomis R, Claret M - Front Neurosci (2015)

Bottom Line: However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood.MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism.In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain ; Department of Endocrinology and Nutrition, School of Medicine, Hospital Clínic, University of Barcelona Barcelona, Spain ; CIBER de Diabetes y Enfermedades Metabólicas Asociadas Barcelona, Spain.

ABSTRACT
The hypothalamus is a crucial central nervous system area controlling appetite, body weight and metabolism. It consists in multiple neuronal types that sense, integrate and generate appropriate responses to hormonal and nutritional signals partly by fine-tuning the expression of specific batteries of genes. However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood. MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism. In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

No MeSH data available.


Related in: MedlinePlus

Hypothalamic miRNAs control energy balance. (A) Divergent effects of Dicer deletion on survival of hypothalamic neurons. Loss of Dicer in POMC neurons during embryonic development does not interfere with neuronal lineage establishment but leads to post-natal neurodegeneration. In contrast, lack of Dicer in the adult does not interfere with POMC neuron viability. Both experimental manipulations cause hyperphagia and obesity in mice, although the underlying mechanisms are different. (B) Proposed mechanisms of action of miR-200a and miR-103 in neuronal insulin and leptin signaling pathways. This graphical summary is based on reports by Schneeberger et al. (2012), Greenman et al. (2013), Crepin et al. (2014) and Vinnikov et al. (2014). InsR, insulin receptor; LepR, leptin receptor.
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Figure 2: Hypothalamic miRNAs control energy balance. (A) Divergent effects of Dicer deletion on survival of hypothalamic neurons. Loss of Dicer in POMC neurons during embryonic development does not interfere with neuronal lineage establishment but leads to post-natal neurodegeneration. In contrast, lack of Dicer in the adult does not interfere with POMC neuron viability. Both experimental manipulations cause hyperphagia and obesity in mice, although the underlying mechanisms are different. (B) Proposed mechanisms of action of miR-200a and miR-103 in neuronal insulin and leptin signaling pathways. This graphical summary is based on reports by Schneeberger et al. (2012), Greenman et al. (2013), Crepin et al. (2014) and Vinnikov et al. (2014). InsR, insulin receptor; LepR, leptin receptor.

Mentions: In the hypothalamus, Dicer transcript expression is regulated by nutrient availability, pathophysiological conditions of nutrient excess and genetic obesity. Fasting up-regulates Dicer, while the expression of other transcripts implicated in miRNA biogenesis were unaltered. In contrast, genetic and induced rodent models of energy excess exhibited decreased expression of Dicer in the hypothalamus (Schneeberger et al., 2012). These results suggested, for the first time, a potential physiological role for Dicer and miRNA biogenesis in the regulation of systemic energy homeostasis. Consistent with this, adult deletion of Dicer in the ARC caused hyperphagia and obesity, a phenotype that was not the consequence of neuronal cell death (Figure 2A) (Vinnikov et al., 2014).


Hypothalamic miRNAs: emerging roles in energy balance control.

Schneeberger M, Gomez-Valadés AG, Ramirez S, Gomis R, Claret M - Front Neurosci (2015)

Hypothalamic miRNAs control energy balance. (A) Divergent effects of Dicer deletion on survival of hypothalamic neurons. Loss of Dicer in POMC neurons during embryonic development does not interfere with neuronal lineage establishment but leads to post-natal neurodegeneration. In contrast, lack of Dicer in the adult does not interfere with POMC neuron viability. Both experimental manipulations cause hyperphagia and obesity in mice, although the underlying mechanisms are different. (B) Proposed mechanisms of action of miR-200a and miR-103 in neuronal insulin and leptin signaling pathways. This graphical summary is based on reports by Schneeberger et al. (2012), Greenman et al. (2013), Crepin et al. (2014) and Vinnikov et al. (2014). InsR, insulin receptor; LepR, leptin receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325937&req=5

Figure 2: Hypothalamic miRNAs control energy balance. (A) Divergent effects of Dicer deletion on survival of hypothalamic neurons. Loss of Dicer in POMC neurons during embryonic development does not interfere with neuronal lineage establishment but leads to post-natal neurodegeneration. In contrast, lack of Dicer in the adult does not interfere with POMC neuron viability. Both experimental manipulations cause hyperphagia and obesity in mice, although the underlying mechanisms are different. (B) Proposed mechanisms of action of miR-200a and miR-103 in neuronal insulin and leptin signaling pathways. This graphical summary is based on reports by Schneeberger et al. (2012), Greenman et al. (2013), Crepin et al. (2014) and Vinnikov et al. (2014). InsR, insulin receptor; LepR, leptin receptor.
Mentions: In the hypothalamus, Dicer transcript expression is regulated by nutrient availability, pathophysiological conditions of nutrient excess and genetic obesity. Fasting up-regulates Dicer, while the expression of other transcripts implicated in miRNA biogenesis were unaltered. In contrast, genetic and induced rodent models of energy excess exhibited decreased expression of Dicer in the hypothalamus (Schneeberger et al., 2012). These results suggested, for the first time, a potential physiological role for Dicer and miRNA biogenesis in the regulation of systemic energy homeostasis. Consistent with this, adult deletion of Dicer in the ARC caused hyperphagia and obesity, a phenotype that was not the consequence of neuronal cell death (Figure 2A) (Vinnikov et al., 2014).

Bottom Line: However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood.MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism.In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain ; Department of Endocrinology and Nutrition, School of Medicine, Hospital Clínic, University of Barcelona Barcelona, Spain ; CIBER de Diabetes y Enfermedades Metabólicas Asociadas Barcelona, Spain.

ABSTRACT
The hypothalamus is a crucial central nervous system area controlling appetite, body weight and metabolism. It consists in multiple neuronal types that sense, integrate and generate appropriate responses to hormonal and nutritional signals partly by fine-tuning the expression of specific batteries of genes. However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood. MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism. In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

No MeSH data available.


Related in: MedlinePlus