{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Dhar-Mascareno M"],"funding":["NCI NIH HHS"],"pagination":["314-24"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4771697"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["30(3)"],"pubmed_abstract":["Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY(705)Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-γ (PPAR γ) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance."],"journal":["Molecular endocrinology (Baltimore, Md.)"],"pubmed_title":["Hexim1, a Novel Regulator of Leptin Function, Modulates Obesity and Glucose Disposal."],"pmcid":["PMC4771697"],"funding_grant_id":["R15CA169984","R15 CA169984"],"pubmed_authors":["Dhar-Mascareno M","Rouille Y","Mascareno EJ","Ramirez SN","Rozenberg I","Kral JG"],"additional_accession":[]},"is_claimable":false,"name":"Hexim1, a Novel Regulator of Leptin Function, Modulates Obesity and Glucose Disposal.","description":"Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY(705)Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-γ (PPAR γ) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance.","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Mar","modification":"2025-04-25T19:08:13.949Z","creation":"2019-03-27T02:10:09Z"},"accession":"S-EPMC4771697","cross_references":{"pubmed":["26859361"],"doi":["10.1210/me.2015-1211"]}}