Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior

Barahona, María José; Llanos, Paula; Recabal, Antonia; Escobar-Acuña, Kathleen; Elizondo‐Vega, Roberto; Salgado, Magdiel; Ordenes, Patricio; Uribe, Elena; Sepúlveda, Fernando J.; Araneda, Ricardo C.; García-Robles, María De Los Ángeles

doi:10.1002/glia.23267

“…This does not rule out a potentially important role for tanycytes in influencing these processes, but demonstrates that other cells can compensate for the loss of tanycyte function. It also remains possible that the residual tanycytes, which would be alpha-1 and a subset of alpha-2 subtypes, could be major players in the expected metabolic phenotypes [34,35] Furthermore, we have only tested a limited number of potential environmental conditions, and a more prominent role for tanycytes may be revealed in response to other physiological challenges. Finally, there are many other physiological processes that may be tanycyte-regulated that were not tested in this study.…”

Section: Discussionmentioning

confidence: 99%

Ablation of tanycytes of the arcuate nucleus and median eminence increases visceral adiposity and decreases insulin sensitivity in male mice

Yoo

¹

,

Cha

²

,

Kim³

et al. 2019

Preprint

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Tanycytes are radial glial cells located in the mediobasal hypothalamus. Recent studies have proposed that tanycytes play an important role in hypothalamic control of energy homeostasis, although this has not been directly tested. Here, we report the phenotype of mice in which tanycytes of the arcuate nucleus and median eminence were conditionally ablated. Although the CSF-hypothalamic barrier was rendered more permeable, the blood-hypothalamic barrier was not altered. The metabolic effects of tanycyte ablation were likewise moderate. However, we consistently observed a significant increase in visceral fat distribution accompanying insulin insensitivity, but only in male mice, and without an effect on either body weight or food intake. A high-fat diet accelerated overall body weight gain in tanycyte-ablated mice, but the development of visceral adiposity and insulin insensitivity was attenuated. These results clarify the extent to which tanycytes regulate energy metabolism, and indicate a role for tanycytes in controlling body adiposity. Introduction:Tanycytes are radial glia that line the ventricular wall of the mediobasal hypothalamus. These are divided into alpha-and beta-subtypes, based on their dorsoventral position along the third ventricle. They extend elongated foot processes away from the ventricle, which terminate either on blood vessels in the hypothalamic parenchyma or at the ventral pial surface [1]. Beta-tanycytes reside outside the blood-brain barrier, and directly contact fenestrated capillaries in the median eminence [2]. Their location at the interface between the hypothalamus and circulatory system allows tanycytes to regulate a broad range of processes relevant to hypothalamic physiology. These include control of the blood-hypothalamus barrier [3,4], energy and nutrient sensing [5][6][7], and regulation of neurohormone release [8,9]. Tanycytes also express many markers of neural progenitor cells, and have been reported to show limited neurogenic potential [10][11][12].Recently, there has been growing interest in the potential role of tanycytes in regulating energy metabolism [5,13,14]. Tanycytes have been reported to directly sense glucose and amino acid levels in CSF and blood [15][16][17], to actively transport leptin into the hypothalamus [18], and to regulate production and release of thyroid releasing hormone (TRH) [9,19]. However, these studies have not directly investigated whether tanycytes are indeed necessary for regulating these processes. It has thus far not been possible to selectively ablate tanycytes, and to directly observe the resulting effects on metabolism, or any other physiological process. This has been the major obstacle to an accurate understanding of their roles in normal hypothalamic physiology.The development of transgenic mice that express tamoxifen-inducible tanycytespecific Cre recombinase has made it possible to analyze the acute physiological effects of tanycyte ablation [20]. When crossed to mice expressing Cre-dependent Eno2-lsl-DTA [21], Results: 1. Condition...

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“…Using a similar approach, different laboratories developed viral constructs such as adenoviruses [18,44,45] and recombinant adeno-associated virus (rAAV) [14,46] to target tanycytes. As for CreERT2 mouse lines or TAT-Cre, these vectors have been first validated using fluorescent protein such as GFP [18,19,44,45] or tdTomato [14].…”

Section: Viral Modelmentioning

confidence: 99%

“…Using a similar approach, different laboratories developed viral constructs such as adenoviruses [18,44,45] and recombinant adeno-associated virus (rAAV) [14,46] to target tanycytes. As for CreERT2 mouse lines or TAT-Cre, these vectors have been first validated using fluorescent protein such as GFP [18,19,44,45] or tdTomato [14]. While adenoviruses efficiently target the ependymal layer in every ventricle without diffusing in the parenchyma [18,45], rAAV serotype has to be carefully chosen: indeed, some of them are more prone to target neurons such as AAV2 or AAV8, whereas others will target glial cells such as AAV4 or AAVDJ8 [47,48].…”

Section: Viral Modelmentioning

confidence: 99%

“…So far, viruses have been mainly used to silence genes in tanycytes in order to determine their functions from the cellular level to physiology in the intact organism. In this perspectives, Garcia-Robles laboratory developed adenoviruses expressing different shRNA to silence gene expression in rat tanycytes (i.e., Glut2, Glucokinase, Mct1), in order to study their glucose-sensing properties and their impact on mice physiology [18,44,45]. Alternatively, viruses have also been used to express proteins in tanycytes, such as the calcium sensor GCamP6s in order to evaluate on slices the increase in (Ca 2+ ) i in tanycytes in response to stimuli [14].…”

Section: Viral Modelmentioning

confidence: 99%

“…So far, molecular genetic approaches in tanycyte research have been restricted to the expression of Cre recombinase, shRNA, fluorescent reporters, DREADD receptors, or calcium sensors in tanycytes [10,14,44,49]. However, already available tools are become more versatile and sophisticated and could therefore give us new information about tanycyte biology.…”

Section: Future Improvements and Applicationsmentioning

confidence: 99%

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Targeting Tanycytes: Balance between Efficiency and Specificity

Langlet¹

2020

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Tanycytes are peculiar ependymoglial cells lining the bottom and the lateral wall of the third ventricle. For a decade, the utilization of molecular genetic approaches allowed us to make important discoveries about their diverse physiological functions. Here, I review the current methods used to target tanycytes, focusing on their specificity, their efficiency, their limitations, as well as their potential future improvements.specificity? This mini-review aims to describe the current methods used to selectively target tanycytes and study their function. It will also discuss the specificity, the efficiency, and the limitations of these methods as well as new possibilities for their improvements.

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Tanycyte ablation in the arcuate nucleus and median eminence increases obesity susceptibility by increasing body fat content in male mice

Yoo

¹

,

Cha

²

,

Kim

³

et al. 2020

Glia

View full text Add to dashboard Cite

Tanycytes are radial glial cells located in the mediobasal hypothalamus. Recent studies have proposed that tanycytes play an important role in hypothalamic control of energy homeostasis, although this has not been directly tested. Here, we report the phenotype of mice in which tanycytes of the arcuate nucleus and median eminence were conditionally ablated in adult mice. Although the cerebrospinal fluid‐hypothalamic barrier was rendered more permeable following tanycyte ablation, neither the blood‐hypothalamic barrier nor leptin‐induced pSTAT3 activation in hypothalamic parenchyma were affected. We observed a significant increase in visceral fat distribution accompanying insulin insensitivity in male mice, without significant effect on either body weight or food intake. A high‐fat diet tended to accelerate overall body weight gain in tanycyte‐ablated mice, but the development of visceral adiposity and insulin insensitivity was comparable to wildtype. Thermoneutral housing exacerbated fat accumulation and produced a shift away from fat oxidation in tanycyte‐ablated mice. These results clarify the extent to which tanycytes regulate energy balance, and demonstrate a role for tanycytes in regulating fat metabolism.

show abstract

Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior

Cited by 35 publications

References 46 publications

Ablation of tanycytes of the arcuate nucleus and median eminence increases visceral adiposity and decreases insulin sensitivity in male mice

Ablation of tanycytes of the arcuate nucleus and median eminence increases visceral adiposity and decreases insulin sensitivity in male mice

Targeting Tanycytes: Balance between Efficiency and Specificity

Tanycyte ablation in the arcuate nucleus and median eminence increases obesity susceptibility by increasing body fat content in male mice

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