1. An obesogenic feedforward loop involving PPARγ, acyl-CoA binding protein and GABA
- Author
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Gerasimos, Anagnostopoulos, Omar, Motiño, Sijing, Li, Vincent, Carbonnier, Hui, Chen, Valentina, Sica, Sylvère, Durand, Mélanie, Bourgin, Fanny, Aprahamian, Nitharsshini, Nirmalathasan, Romain, Donne, Chantal, Desdouets, Marcelo Simon, Sola, Konstantina, Kotta, Léa, Montégut, Flavia, Lambertucci, Didier, Surdez, Grossetête, Sandrine, Olivier, Delattre, Maria Chiara, Maiuri, José Manuel, Bravo-San Pedro, Isabelle, Martins, and Guido, Kroemer
- Subjects
Diazepam Binding Inhibitor ,PPAR gamma ,Mice ,Receptors, GABA ,Animals ,Coenzyme A ,Carrier Proteins ,Receptors, GABA-A ,Weight Gain ,gamma-Aminobutyric Acid - Abstract
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 (GABA
- Published
- 2022