A novel role for central <scp>ACBP</scp>/<scp>DBI</scp> as a regulator of long‐chain fatty acid metabolism in astrocytes

Bouyakdan, Khalil; Taïb, Bouchra; Budry, Lionel; Zhao, Shangang; Rodaros, Demetra; Neess, Ditte; Mandrup, Susanne; Færgeman, Nils J.; Alquier, Thierry

doi:10.1111/jnc.13035

Cited by 55 publications

(58 citation statements)

References 52 publications

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“…Acyl CoA binding protein can be found primarily around the outside of the tissue and is likely present in the dura mater region of the meninges. This protein is also known as the diazepam binding inhibitor (GABA receptor modulator), which has been implicated in regulating neurogenesis in the brain stem cells [21] and long-chain fatty acid metabolism in astrocytes [22]. The localization to the meninges is further supported by the 2-D ion images shown at the bottom of Figure 2c.…”

Section: Resultsmentioning

confidence: 87%

3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma

Anderson

Plas

Rose

et al. 2016

Journal of Proteomics

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Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions.

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Section: Resultsmentioning

confidence: 87%

3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma

Anderson

Plas

Rose

et al. 2016

Journal of Proteomics

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“…Once transported into the cell, LCFAs are esterified by acyl-CoA-binding protein (ACBP), a protein that is ubiquitously expressed in tissues with high lipid turnover. Interestingly, ACBP is expressed in the hypothalamus and may play a role in the LCFA sensing by hypothalamic astrocytes (25). …”

Section: Neuronal Uptake Of Lipids and Fasmentioning

confidence: 99%

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

2017

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Metabolic disorders, particularly aberrations in lipid homeostasis, such as obesity, type 2 diabetes mellitus, and hypertriglyceridemia often manifest together as the metabolic syndrome (MetS). Despite major advances in our understanding of the pathogenesis of these disorders, the prevalence of the MetS continues to rise. It is becoming increasingly apparent that intermediary metabolism within the central nervous system is a major contributor to the regulation of systemic metabolism. In particular, lipid metabolism within the brain is tightly regulated to maintain neuronal structure and function and may signal nutrient status to modulate metabolism in key peripheral tissues such as the liver. There is now a growing body of evidence to suggest that fatty acid (FA) sensing in hypothalamic neurons via accumulation of FAs or FA metabolites may signal nutritional sufficiency and may decrease hepatic glucose production, lipogenesis, and VLDL-TG secretion. In addition, recent studies have highlighted the existence of liver-related neurons that have the potential to direct such signals through parasympathetic and sympathetic nervous system activity. However, to date whether these liver-related neurons are FA sensitive remain to be determined. The findings discussed in this review underscore the importance of the autonomic nervous system in the regulation of systemic metabolism and highlight the need for further research to determine the key features of FA neurons, which may serve as novel therapeutic targets for the treatment of metabolic disorders.

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“…The anorexigenic effect of endozepines does not depend on CBR or PBR signaling, but solely on ODN-GPCR signaling, since it is blunted by co-treatment with a selective ODN-GPCR antagonist (do Rego et al, 2007; Lanfray et al, 2013). Although, DBI mRNA and immunoreactivity has been found both in neurons and astrocytes (Alho et al, 1985, 1989; Tonon et al, 1990; Bouyakdan et al, 2015), DBI is mainly expressed in non-neuronal cells, such as ependymocytes, tanycytes, and proteoplasmic astrocytes (Tong et al, 1991; Lanfray et al, 2013; Bouyakdan et al, 2015). Consistent with a role of glial endozepines as anorexigenic factors, food deprivation reduces the mRNA expression of DBI in ependymocytes bordering the third and lateral ventricle as well as in median eminence tanycytes and arcuate protoplasmic astrocytes (Compère et al, 2010; Lanfray et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

et al. 2017

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Endozepines are endogenous ligands for the benzodiazepine receptors and also target a still unidentified GPCR. The endozepine octadecaneuropeptide (ODN), an endoproteolytic processing product of the diazepam-binding inhibitor (DBI) was recently shown to be involved in food intake control as an anorexigenic factor through ODN-GPCR signaling and mobilization of the melanocortinergic signaling pathway. Within the hypothalamus, the DBI gene is mainly expressed by non-neuronal cells such as ependymocytes, tanycytes, and protoplasmic astrocytes, at levels depending on the nutritional status. Administration of ODN C-terminal octapeptide (OP) in the arcuate nucleus strongly reduces food intake. Up to now, the relevance of extrahypothalamic targets for endozepine signaling-mediated anorexia has been largely ignored. We focused our study on the dorsal vagal complex located in the caudal brainstem. This structure is strongly involved in the homeostatic control of food intake and comprises structural similarities with the hypothalamus. In particular, a circumventricular organ, the area postrema (AP) and a tanycyte-like cells forming barrier between the AP and the adjacent nucleus tractus solitarius (NTS) are present. We show here that DBI is highly expressed by ependymocytes lining the fourth ventricle, tanycytes-like cells, as well as by proteoplasmic astrocytes located in the vicinity of AP/NTS interface. ODN staining observed at the electron microscopic level reveals that ODN-expressing tanycyte-like cells and protoplasmic astrocytes are sometimes found in close apposition to neuronal elements such as dendritic profiles or axon terminals. Intracerebroventricular injection of ODN or OP in the fourth ventricle triggers c-Fos activation in the dorsal vagal complex and strongly reduces food intake. We also show that, similarly to leptin, ODN inhibits the swallowing reflex when microinjected into the swallowing pattern generator located in the NTS. In conclusion, we hypothesized that ODN expressing cells located at the AP/NTS interface could release ODN and modify excitability of NTS neurocircuitries involved in food intake control.

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A novel role for central ACBP/DBI as a regulator of long‐chain fatty acid metabolism in astrocytes

Cited by 55 publications

References 52 publications

3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma

3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma

Lipid Processing in the Brain: A Key Regulator of Systemic Metabolism

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

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