| Title: |
ADH1B, the adipocyte-enriched alcohol dehydrogenase, plays an essential, cell-autonomous role in human adipogenesis |
| Authors: |
Gautheron, Jérémie; Elsayed, Solaf; Pistorio, Valeria; Lockhart, Sam; Zammouri, Jamila; Auclair, Martine; Koulman, Albert; Meadows, Sarah, R; Lhomme, Marie; Ponnaiah, Maharajah; Si-Bouaz, Redouane; Fabrega, Sylvie; Belkadi, Abdelaziz; O’rahilly, Stephen; Delaunay, Jean-Louis; Aït-Slimane, Tounsia; Fève, Bruno; Vigouroux, Corinne; Ghaffar, Tawhida, y Abdel; O'Rahilly, Stephen; Jéru, Isabelle |
| Contributors: |
Centre de Recherche Saint-Antoine (CRSA); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU); Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition CHU Pitié Salpêtrière (IHU ICAN); CHU Pitié-Salpêtrière AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); جامعة عين شمس - Ain Shams University Cairo (ASU); University of Cambridge Cambridge, UK (CAM); Structure Fédérative de Recherche Necker (UAR 3633 / US24); Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité); Mitochondrie : Régulations et Pathologie; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM); Génétique Humaine des Maladies Infectieuses (Inserm U980); Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM); Weill Cornell Medicine Qatar; CHU Saint-Antoine AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU); Sorbonne Université (SU); ANR-21-CE17-0002,DELFAT,Sauver les greffons hépatiques stéatosiques en modulant l'activité de la nécroptose(2021) |
| Source: |
ISSN: 0027-8424. |
| Publisher Information: |
CCSD; National Academy of Sciences |
| Publication Year: |
2024 |
| Subject Terms: |
Alcohol dehydrogenase 1B (ADH1B) Adipocyte differentiation 9-cis Retinoic Acid Human adipose stem cells (ASCs) REAGENT or RESOURCE SOURCE IDENTIFIER Antibodies Anti-ADH1B Protein Tech; Alcohol dehydrogenase 1B (ADH1B); Adipocyte differentiation; 9-cis Retinoic Acid; [SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Alcohol dehydrogenase 1B (ADH1B) is a primate-specific enzyme which, uniquely among the ADH class 1 family, is highly expressed both in adipose tissue and liver. Its expression in adipose tissue is reduced in obesity and increased by insulin stimulation. Interference with ADH1B expression has also been reported to impair adipocyte function. To better understand the role of ADH1B in adipocytes, we used CRISPR/Cas9 to delete ADH1B in human adipose stem cells (ASC). Cells lacking ADH1B failed to differentiate into mature adipocytes manifested by minimal triglyceride accumulation and a marked reduction in expression of established adipocyte markers. As ADH1B is capable of converting retinol to retinoic acid (RA), we conducted rescue experiments. Incubation of ADH1B-deficient preadipocytes with 9-cis-RA, but not with all-transretinol, significantly rescued their ability to accumulate lipids and express markers of adipocyte differentiation. A homozygous missense variant in ADH1B (p.Arg313Cys) was found in a patient with congenital lipodystrophy of unknown cause. This variant significantly impaired the protein’s dimerization, enzymatic activity, and its ability to rescue differentiation in ADH1B-deficient ASC. The allele frequency of this variant in the Middle Eastern population suggests that it is unlikely to be a fully penetrant cause of severe lipodystrophy. In conclusion, ADH1B appears to play an unexpected, crucial and cell-autonomous role in human adipocyte differentiation by serving as a necessary source of endogenous retinoic acid. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38838011; PUBMED: 38838011 |
| DOI: |
10.1073/pnas.2319301121 |
| Availability: |
https://hal.sorbonne-universite.fr/hal-04603878; https://hal.sorbonne-universite.fr/hal-04603878v1/document; https://hal.sorbonne-universite.fr/hal-04603878v1/file/gautheron-et-al-2024-adh1b-the-adipocyte-enriched-alcohol-dehydrogenase-plays-an-essential-cell-autonomous-role-in.pdf; https://doi.org/10.1073/pnas.2319301121 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.42FDAC76 |
| Database: |
BASE |