Neutralization of DBI/ACBP for the prevention of ciliopathy-associated obesity - PubMed
14 hours ago
- #obesity
- #ciliopathy
- #autophagy
- Obesity is a feature of certain ciliopathies, including Alström syndrome caused by ALMS1 deficiency.
- DBI/ACBP was identified as a central driver of ciliopathy-associated obesity through multi-omics network analysis in Alms1-deficient mice.
- ALMS1 deficiency leads to early hepatic dyslipidemia, impaired autophagy, and pathological accumulation of DBI/ACBP before obesity onset.
- Prophylactic neutralization of DBI/ACBP with monoclonal antibodies prevents weight gain and metabolic alterations without restoring autophagy markers.
- DBI/ACBP acts as an obesogenic effector downstream or parallel to defective autophagy.
- Therapeutic benefits can be achieved by targeting autophagy-linked effectors like DBI/ACBP without directly correcting autophagic flux.
- DBI/ACBP serves as a mechanistic link between ciliary dysfunction, altered autophagy, and metabolic disease.