Glial endozepines and energy balance: Old peptides with new tricks

Abstract

The contribution of neuroglial interactions to the regulation of energy balance has gained increasing acceptance in recent years. In this context, endozepines, endogenous analogs of benzodiazepine derived from diazepam‐binding inhibitor, are now emerging as major players. Produced by glial cells (astrocytes and tanycytes), endozepines have been known for two decades to exert potent anorexigenic effects by acting at the hypothalamic level. However, it is only recently that their modes of action, including the mechanisms by which they modulate energy metabolism, have begun to be elucidated. The data available today are abundant, significant, and sometimes contradictory, revealing a much more complex regulation than initially expected. Several mechanisms of action of endozepines seem to coexist at the central level, particularly in the hypothalamus. The brainstem has also recently emerged as a potential site of action for endozepines. In addition to their central anorexigenic effects, endozepines may also display peripheral effects promoting orexigenic actions, adding to their complexity and raising yet more questions. In this review, we attempt to provide an overview of our current knowledge in this rapidly evolving field and to pinpoint questions that remain unanswered.

Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index

“…Acyl-coenzyme A binding protein (ACBP), also called diazepam-binding inhibitor (DBI) is a phylogenetically ancient protein with two distinct functions 1 , 2 . As an intracellular protein, ACBP/DBI binds, buffers and transports medium-size acyl-coenzyme A molecules, hence contributing to lipid metabolism 3 , 4 . As an extracellular protein, ACBP/DBI binds to γ-aminobutyric acid (GABA) receptors of the A type (GABA A R) 5 , 6 , and at least within the central nervous system, to other neurotransmitter receptors (such as the ODN receptors) as well 7 , 8 .…”

“…As an extracellular protein, ACBP/DBI binds to γ-aminobutyric acid (GABA) receptors of the A type (GABA A R) 5 , 6 , and at least within the central nervous system, to other neurotransmitter receptors (such as the ODN receptors) as well 7 , 8 . Hence, ACBP/DBI participates in paracrine and neuroendocrine signaling 4 .…”

Circulating diazepam‐binding inhibitor in infancy: Relation to markers of adiposity and metabolic health

“…22 Nevertheless, a cross-talk between circulating DBI and the central nervous system concerning the control of energy balance is conceivable, and it is likely that DBI reaches the glial cells as well as hypothalamic regions involved in feeding behavior located outside the blood-brain barrier through so far undefined mechanisms. 23 The lower fat mass exhibited by SGA infants in late infancy could result from an impaired adipogenesis. We recently reported that GPR120 -a key regulator of adipogenesis-is hypermethylated in cord blood of SGA newborns and also in peripheral blood at age 1 year and is associated with lower fat mass at the age of 1 and 2 years.…”

Glial Modulation of Energy Balance: The Dorsal Vagal Complex Is No Exception

“…These isoforms may play a role in receptor-mediated leptin transport from the AP to the NTS [19]. More recently, vagliocytes were reported to express octadecaneuropeptide (ODN), a glial anorexigenic peptide [42]. By contrast, AP is virtually devoid of GFAP+ astrocytes.…”

“…Endozepines are well known endogenous ligands of benzodiazepine (BZ) receptors (see [130] for review). Over the last two decades, evidence has accumulated that strongly suggests that endozepines could act as endogenous modulators of energy balance by acting at the hypothalamic level [42,130]. The icv injection of ODN dose-dependently reduced food intake in fasted and ad libitum-fed rodents [131][132][133][134][135].…”