Identification of ACBP as a potential target in ciliopathic obesity through multi-omics network analysis

Ciliopathies are genetic disorders characterized by defective primary cilia function, with obesity as a clinical manifestation in certain cases, including Alström syndrome, which is caused by ALMS1 mutations. The link between cilia and lipid metabolism remains poorly understood, but evidence suggests a role for impaired autophagy. Autophagy affects both intra- and extracellular levels of ACBP, which can act as an obesogenic factor. Our multi-omics study reveals early hepatic dyslipidemia, impaired autophagy, and hepatic accumulation of ACBP in presymptomatic male mice lacking Alms1 gene. These conditions are consistent with the obesogenic phenotype and with alterations in the gut microbiota that manifest as the mice age and develop obesity. Importantly, reducing excessive ACBP with a neutralizing monoclonal antibody limits weight gain and metabolic defects in Alms1<sup>-/-</sup> mice in an autophagy-independent manner. Altogether, the data support the idea that ciliopathy-associated obesity, particularly Alström syndrome, may be mitigated by ACBP neutralization.

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Journal
Nature Communications
Published
2026-01-09
DOI
https://doi.org/10.1038/s41467-025-66235-4
Citations
1
Primary Topic
Genetic and Kidney Cyst Diseases
Type
article
Field-Weighted Citation Impact
30.93

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article

Identification of ACBP as a potential target in ciliopathic obesity through multi-omics network analysis

Francisco Javier Cubero, María Pérez-Lanzón, Paula Moreno-Cruz, Yulia Alexandrowna Nevzorova et al.
1 citations
Nature Communications
Genetic and Kidney Cyst Diseases
30.93
article

Identification of ACBP as a potential target in ciliopathic obesity through multi-omics network analysis

Francisco Javier Cubero, María Pérez-Lanzón, Paula Moreno-Cruz, Yulia Alexandrowna Nevzorova, Yaiza Corral Nieto, Valentina Sica, Laura Ventura-San Pedro, Oscar J. Pozo, Ana Elena Pérez-Cobas, José Manuel Bravo-San Pedro, Laura Manrique, Amanda Gabrielly Fernández Pereira, Héctor Leal Lassalle, Élida Alechaga, José Manuel Fuentes, Patricia Boya, Rocío Benítez-Fernández, Sylvere Durand, Sonia Belén Paredes
article en
1 citations

Abstract

Ciliopathies are genetic disorders characterized by defective primary cilia function, with obesity as a clinical manifestation in certain cases, including Alström syndrome, which is caused by ALMS1 mutations. The link between cilia and lipid metabolism remains poorly understood, but evidence suggests a role for impaired autophagy. Autophagy affects both intra- and extracellular levels of ACBP, which can act as an obesogenic factor. Our multi-omics study reveals early hepatic dyslipidemia, impaired autophagy, and hepatic accumulation of ACBP in presymptomatic male mice lacking Alms1 gene. These conditions are consistent with the obesogenic phenotype and with alterations in the gut microbiota that manifest as the mice age and develop obesity. Importantly, reducing excessive ACBP with a neutralizing monoclonal antibody limits weight gain and metabolic defects in Alms1<sup>-/-</sup> mice in an autophagy-independent manner. Altogether, the data support the idea that ciliopathy-associated obesity, particularly Alström syndrome, may be mitigated by ACBP neutralization.

Nature CommunicationsVol. 17(1)
Universidad Complutense de Madrid (ES), Centre National de la Recherche Scientifique (FR), University of Fribourg (CH), Inserm (FR), Universitat Pompeu Fabra (ES), Institut Universitaire de France (FR), Université Paris Cité (FR), Instituto Cajal (ES), Université Paris-Saclay (FR), Barcelona Supercomputing Center (ES), Instituto de Salud Carlos III (ES), Institut Gustave Roussy (FR), Hospital General Universitario Gregorio Marañón (ES), Sorbonne Université (FR), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Centre de Recherche des Cordeliers (FR), Hôpital Européen Georges-Pompidou (FR), Centro de Investigación Biomédica en Red (ES), Instituto Ramón y Cajal de Investigación Sanitaria (ES), Hospital Del Mar (ES), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES), Institute of Parasitology (CZ), Universidad de Extremadura (ES), Universitat Politècnica de Catalunya (ES)
Comunidad de Madrid, European Commission, Instituo Cajal, Barcelona Supercomputing Center, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Universidad de Extremadura, Instituto de Salud Carlos III, Agencia Estatal de Investigación, European Social Fund
Good health and well-being
Openalex Percentile: Top 2%
Genetic and Kidney Cyst Diseases
30.93
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