From benzodiazepines to fatty acids and beyond: revisiting the role of ACBP/DBI

Alquier, Thierry; Christian‐Hinman, Catherine A.; Alfonso, Julieta; Færgeman, Nils J.

doi:10.1016/j.tem.2021.08.009

Cited by 24 publications

(29 citation statements)

References 107 publications

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“…ACBP/DBI (hereafter referred to as ACBP) is a phylogenetically ancient protein that is usually contained in the cytoplasm of nucleated cells, where it interacts with activated medium-chain fatty acids and participates in lipid metabolism [ 12 , 13 ]. Being a leaderless peptide, it does not undergo conventional protein secretion However, it can be released into the extracellular space through an autophagy-associated pathway [ 9 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABAA receptor

Anagnostopoulos

Motiño

et al. 2022

Cell Death Dis

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Acyl-coenzyme-A-binding protein (ACBP), also known as a diazepam-binding inhibitor (DBI), is a potent stimulator of appetite and lipogenesis. Bioinformatic analyses combined with systematic screens revealed that peroxisome proliferator-activated receptor gamma (PPARγ) is the transcription factor that best explains the ACBP/DBI upregulation in metabolically active organs including the liver and adipose tissue. The PPARγ agonist rosiglitazone-induced ACBP/DBI upregulation, as well as weight gain, that could be prevented by knockout of Acbp/Dbi in mice. Moreover, liver-specific knockdown of Pparg prevented the high-fat diet (HFD)-induced upregulation of circulating ACBP/DBI levels and reduced body weight gain. Conversely, knockout of Acbp/Dbi prevented the HFD-induced upregulation of PPARγ. Notably, a single amino acid substitution (F77I) in the γ2 subunit of gamma-aminobutyric acid A receptor (GABAAR), which abolishes ACBP/DBI binding to this receptor, prevented the HFD-induced weight gain, as well as the HFD-induced upregulation of ACBP/DBI, GABAAR γ2, and PPARγ. Based on these results, we postulate the existence of an obesogenic feedforward loop relying on ACBP/DBI, GABAAR, and PPARγ. Interruption of this vicious cycle, at any level, indistinguishably mitigates HFD-induced weight gain, hepatosteatosis, and hyperglycemia.

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Section: Introductionmentioning

confidence: 99%

An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABAA receptor

Anagnostopoulos

Motiño

et al. 2022

Cell Death Dis

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“…Collectively, these results suggest that lipid droplets undergo dramatic remodelling in response to changing metabolic demands in nutrientrich conditions and Acb1 is required for regulating the remodelling of lipid droplets. Supplement of oleate restores tubular mitochondria structure in cells lacking Acb1 but does not affect lipid droplets, cell growth and cell viability ACBP/Acb1 is able to relieve the inhibitory effect of LCACoAs on fatty acid synthases, acyl-CoA carboxylases and acyl-CoA synthetases [12]. Therefore, it is conceivable that the absence of Acb1 could alter the cellular profile of fatty acids.…”

Section: Acb1 Is Required For Remodelling Lipid Dropletsmentioning

confidence: 99%

“…Emerging evidence shows that ACBP can be secreted into the extracellular environment via the unconventional secretory pathway [15][16][17][18][19][20]. The secreted ACBP and its derivatives have been shown to play crucial roles in regulating neuronal functions, lipogenesis and hormone secretion [12,21]. Despite significant progress in understanding ACBP functions, how ACBP is involved in regulating mitochondrial morphology, mitochondrial functions and lipid droplets has been elusive.…”

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confidence: 99%

The acyl‐CoA‐binding protein Acb1 regulates mitochondria, lipid droplets, and cell proliferation

Liu

Zheng

et al. 2022

FEBS Letters

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Mitochondria are involved in many cellular activities, including energy metabolism and biosynthesis of nucleotides, fatty acids and amino acids. Mitochondrial morphology is a key factor in dictating mitochondrial functions. Here, we report that the acyl-CoA-binding protein (ACBP) Acb1 in the fission yeast Schizosaccharomyces pombe is required for the maintenance of tubular mitochondrial morphology and proper mitochondrial respiration. The absence of Acb1 causes severe mitochondrial fragmentation in a dynaminrelated protein Dnm1-dependent manner and impairs mitochondrial respiration. Moreover, Acb1 regulates the remodelling of lipid droplets in nutrientrich conditions. Importantly, Acb1 promotes cell survival when cells are cultured in nutrient-rich medium. Hence, our findings establish roles of ACBP in regulating mitochondria, lipid droplets and cell viability.

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“…Autophagy and lipophagy, a form of selective autophagy, are regulated by different factors including acyl-coA-binding protein (ACBP). This protein, also known as diazepam binding inhibitor (DBI), is involved in intracellular bioenergetic reactions and serves as an extracellular feedback inhibitor of autophagy [ 19 , 20 , 21 ]. ACBP is conserved in eukaryotes and is expressed by all nucleated cells, underscoring its importance as a cellular metabolic hub.…”

Section: Introductionmentioning

confidence: 99%

“…Within cells, ACBP binds to activated, acyl-coA-bound medium-chain fatty acids and shuttles them between cellular organelles for energy production. While intracellular ACBP has been shown to promote autophagy, lipophagy, and oxidative phosphorylation [ 22 , 23 ], secreted extracellular ACBP inhibits autophagy and stimulates appetite to increase nutrient uptake [ 19 , 20 , 21 , 24 ]. Hence, ACBP can be considered a metabolic and neuroendocrine factor that regulates bioenergetic and cellular functions in a context-dependent manner [ 21 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Distinct Plasma Concentrations of Acyl-CoA-Binding Protein (ACBP) in HIV Progressors and Elite Controllers

Isnard

Royston

Lin

et al. 2022

Viruses

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HIV elite controllers (ECs) are characterized by the spontaneous control of viral replication, and by metabolic and autophagic profiles which favor anti-HIV CD4 and CD8 T-cell responses. Extracellular acyl coenzyme A binding protein (ACBP) acts as a feedback inhibitor of autophagy. Herein, we assessed the circulating ACBP levels in ECs, compared to people living with HIV (PLWH) receiving antiretroviral therapy (ART) or not. We found lower ACBP levels in ECs compared to ART-naïve or ART-treated PLWH (p < 0.01 for both comparisons), independently of age and sex. ACBP levels were similar in ECs and HIV-uninfected controls. The expression of the protective HLA alleles HLA-B*27, *57, or *58 did not influence ACBP levels in ECs. ACBP levels were not associated with CD4 or CD8 T-cell counts, CD4 loss over time, inflammatory cytokines, or anti-CMV IgG titers in ECs. In ART-treated PLWH, ACBP levels were correlated with interleukin (IL)-1β levels, but not with other inflammatory cytokines such as IL-6, IL-8, IL-32, or TNF-α. In conclusion, ECs are characterized by low ACBP plasma levels compared to ART-naïve or ART-treated PLWH. As autophagy is key to anti-HIV CD4 and CD8 T-cell responses, the ACBP pathway constitutes an interesting target in HIV cure strategies.

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From benzodiazepines to fatty acids and beyond: revisiting the role of ACBP/DBI

Cited by 24 publications

References 107 publications

An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABAA receptor

An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABAA receptor

The acyl‐CoA‐binding protein Acb1 regulates mitochondria, lipid droplets, and cell proliferation

Distinct Plasma Concentrations of Acyl-CoA-Binding Protein (ACBP) in HIV Progressors and Elite Controllers

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