ACBP is an appetite stimulator across phylogenetic barriers

Madeo, Frank; Tavernarakis, Nektarios; Pedro, José Manuel Bravo-San; Kroemer, Guido

doi:10.15698/cst2020.02.211

Cited by 7 publications

(9 citation statements)

References 10 publications

(14 reference statements)

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“…Thus, ACBP/DBI levels are abnormally low in patients with anorexia nervosa 12 , 21 , but high in patients with obesity 12 , 20 . Thus, ACBP/DBI is among the rare appetite-stimulatory factors that increases in human obesity 20 , 22 , contrasting with many other appetite-stimulatory mediators (as prominently exemplified by ghrelin) that are rather reduced in non-syndromic obesity 23 , 24 . Hence, ACBP/DBI could be causally involved in human obesity, a hypothesis that requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3–9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…ACBP/DBI plays a major role in the control of appetite and metabolism through a phylogenetically conserved pathway that is conserved in yeast, nematodes, insects and mammals (15,20,21,40).…”

Section: Discussionmentioning

confidence: 99%

“…ACBP/DBI plays a major role in the control of appetite and metabolism through a phylogenetically conserved pathway that is conserved in yeast, nematodes, insects, and mammals ( 15 , 20 , 21 , 40 ). Intrigued by the observation that ACBP/DBI is a highly conserved protein that is even encoded by some bacterial genes, as well as by the link between human obesity and the gut microbiome, we investigated the prevalence of ACBP/DBI in intestinal commensals and their potential correlation with the body mass index.…”

Section: Discussionmentioning

confidence: 99%

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Genes Encoding Microbial Acyl Coenzyme A Binding Protein/Diazepam-Binding Inhibitor Orthologs Are Rare in the Human Gut Microbiome and Show No Links to Obesity

Thomas

Asnicar

Kroemer

et al. 2021

Appl Environ Microbiol

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Acyl coenzyme A (CoA) binding protein (ACBP), also called diazepam-binding inhibitor (DBI) is a phylogenetically conserved protein that is expressed by all eukaryotic species as well as by some bacteria. Since elevated ACBP/DBI levels play a major role in the inhibition of autophagy, increase in appetite and lipoanabolism that accompany obesity, we wondered whether ACBP/DBI produced by the human microbiome might affect host weight. We found that the genomes of bacterial commensals rarely contain ACBP/DBI homologues, which are rather encoded by genomes of some pathogenic or environmental taxa that were not prevalent in human feces. Exhaustive bioinformatic analyses of 1,899 gut samples from healthy individuals refuted the hypothesis that bacterial ACBP/DBI might affect the BMI in a physiological context. Thus, the physiological regulation of BMI is unlikely to be affected by microbial ACBP/DBI-like proteins. However, at the speculative level, it remains possible that ACBP/DBI produced by potential pathogenic bacteria might enhance their virulence by inhibiting autophagy and hence subverting innate immune responses. Importance Acyl coenzyme A (CoA) binding protein (ACBP) can be encoded by several organisms across the domains of life, including microbes, and has shown to play major roles in human metabolic processes. However, little is known about its presence in the human gut microbiome and whether its microbial counterpart could also play a role in human metabolism. In the present study, we found that microbial ACBP/DBI sequences were rarely present in the gut microbiome across multiple metagenomic datasets. Microbes that carried ACBP/DBI in the human gut microbiome included Saccharomyces cerevisiae, Lautropia mirabilis and Comamonas kerstersii, but these microorganisms were not associated with body-mass index, further indicating an unconvincing role for microbial ACBP/DBI in human metabolism.

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“…This latter effect involves GABA receptors of the A type (GABAAR) because mice bearing a point mutation (F77I) in the GABAAR 2 subunit that reduces ACBP/DBI binding [ 31 ] fail to increase food intake after ACBP/DBI injection [ 24 ]. Thus, the starvation-induced surge in plasma ACBP/DBI may be part of a “hunger reflex” assuring the maintenance of energy and body mass homeostasis [ 32 , 33 ]. As true for most if not all homeostatic circuitries, this “hunger reflex” would involve a negative feedback loop in which extracellular ACBP/DBI acting on GABAAR would be embedded ( Fig.…”

Section: Acbp/dbi In the Pathogenesis Of Obesitymentioning

confidence: 99%

Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects

Li¹,

Joseph²,

Martins³

et al. 2021

CST

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Eukaryotic cells release the phylogenetically ancient protein acyl coenzyme A binding protein (ACBP, which in humans is encoded by the gene DBI, diazepam binding inhibitor) upon nutrient deprivation. Accordingly, mice that are starved for one to two days and humans that undergo voluntary fasting for one to three weeks manifest an increase in the plasma concentration of ACBP/DBI. Paradoxically, ACBP/DBI levels also increase in obese mice and humans. Since ACBP/DBI stimulates appetite, this latter finding may explain why obesity constitutes a self-perpetuating state. Here, we present a theoretical framework to embed these findings in the mechanisms of weight control, as well as a bioinformatics analysis showing that, irrespective of the human cell or tissue type, one single isoform of ACBP/DBI (ACBP1) is preponderant (~90% of all DBI transcripts, with the sole exception of the testis, where it is ~70%). Based on our knowledge, we conclude that ACBP1 is subjected to a biphasic transcriptional and post-transcriptional regulation, explaining why obesity and fasting both are associated with increased circulating ACBP1 protein levels.

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ACBP is an appetite stimulator across phylogenetic barriers

Cited by 7 publications

References 10 publications

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

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

Genes Encoding Microbial Acyl Coenzyme A Binding Protein/Diazepam-Binding Inhibitor Orthologs Are Rare in the Human Gut Microbiome and Show No Links to Obesity

Elevated plasma levels of the appetite-stimulator ACBP/DBI in fasting and obese subjects

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