Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance

Glial endozepines and energy balance: Old peptides with new tricks

“…However, i.c.v. administration of PK11195 in the third ventricle was recently shown to induce delayed anorexia 8–24 hr postinjection both in NC‐ and HFD‐fed mice, as well as an increase in energy expenditure (Kim et al, 2019). Although this result does not invalidate the previous demonstrations that ODN‐GPCR pharmacological activation triggers anorexia, it shows that additional effects of endozepines on energy homeostasis could involve their action on TSPO.…”

“…In the MBH, the expression of TSPO is restricted to glial cells and is present at particularly high levels within tanycytes and ependymocytes lining the third ventricle. Relatively less abundant TSPO expression is also detected in ARC microglial cells, whereas TSPO is barely detected in GFAP‐positive astrocytes (Kim et al, 2019). Using an immortalized hypothalamic cell line presenting some characteristics overlapping with the characteristics of tanycytes, A2/29 cells, Kim et al have further explored the mechanisms by which central treatment with PK11195 can induce a negative energy balance in mice (S. Kim et al, 2019).…”

Targeting Tanycytes: Balance between Efficiency and Specificity

“…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].…”

“…In this perspective, 3 different constructs have been built using the promoter of Dio2 [14], Tshr [49], and Rax [46] genes. Introduced in AAV or adenoviral vectors that incorporate the ependymal layer without targeting parenchymal cells, these promoters only drive an expression of the protein of interest (i.e., Cre recombinase [14,46] or Gcamp3 [49]) in the tanycyte population. Alternatively, Müller-Fielitz et al [14] com- Fig.…”

“…Some of them are suggested here. The combination of tools targeting only the ependymal layer (e.g., adenoviruses, AAV1/2) and tanycyte marker promoter (e.g., Rax [46], Dio2 [14], Tshr [49]) will allow us to specifically study tanycyte populations and to make significant advances in the understanding of their functions. AAV, adeno-associated virus; ARH, arcuate nucleus; VMH, ventromedial nucleus; DMH, dorsomedial nucleus.…”