ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Molecular Endocrinology -Baltimore- Année : 2015

ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content

Résumé

Individuals who are born small for gestational age (SGA) have a risk to develop various metabolic diseases during their life course. The biological memory of the prenatal state of growth restricted individuals may be reflected in epigenetic alterations in stem cell populations. Mesenchymal stem cells (MSCs) from the Wharton's jelly of umbilical cord tissue are multipotent, and we generated primary umbilical cord MSC isolates from SGA and normal neonates, which were subsequently differentiated into adipocytes. We established chromatin state maps for histone marks H3K27 acetylation and H3K27 trimethylation and tested whether enrichment of these marks was associated with gene expression changes. After validating gene expression levels for 10 significant chromatin immunoprecipitation sequencing candidate genes, we selected acyl-coenzyme A synthetase 1 (ACSL1) for further investigations due to its key roles in lipid metabolism. The ACSL1 gene was found to be highly associated with histone acetylation in adipocytes differentiated from MSCs with SGA background. In SGA-derived adipocytes, the ACSL1 expression level was also found to be associated with increased lipid loading as well as higher insulin sensitivity. ACSL1 depletion led to changes in expression of candidate genes such as proinflammatory chemokines and down-regulated both, the amount of cellular lipids and glucose uptake. Increased ACSL1, as well as modulated downstream candidate gene expression, may reflect the obese state, as detected in mice fed a high-fat diet. In summary, we believe that ACSL1 is a programmable mediator of insulin sensitivity and cellular lipid content and adipocytes differentiated from Wharton's jelly MSCs recapitulate important physiological characteristics of SGA individuals.

Dates et versions

inserm-02454551 , version 1 (24-01-2020)

Identifiants

Citer

Roy Joseph, Jérémie Poschmann, Rami Sukarieh, Peh Gek Too, Sofi Julien, et al.. ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content. Molecular Endocrinology -Baltimore-, 2015, 29 (6), pp.909-920. ⟨10.1210/me.2015-1020⟩. ⟨inserm-02454551⟩

Collections

INSERM
12 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More