title: Tnfα, Cox2 and AdipoQ adipokine gene expression levels are modulated in murine adipose tissues by both nicotine and nACh receptors containing the β2 subunit.
abstract: Studies have provided evidences for the effects of nicotine on adipose tissues, as well as in inflammatory response. We hypothesized that nicotine affects adipokine gene expression in adipose tissues via specific neuronal nicotinic acetylcholine receptors (nAChRs). First, we described the expression of multiple nAChR subunit genes in mouse white and brown adipose tissues (WAT and BAT), and detected differential expression in WAT and BAT (α2>α5>β2 and α2>β2>β4, respectively). Additionally, when nicotine was administered to wild-type mice, it significantly affected the expression of adipokine genes, such as Tnfα, AdipoQ, Haptoglobin and Mcp1 in WAT. Next, we demonstrated that in mice deficient for the β2 nAChR subunit (β2-/- mice), the expression levels of Cox2 and Ngfβ genes in WAT, and Leptin, Cox2, AdipoQ and Haptoglobin in BAT, were significantly altered. Furthermore, interactions between mouse β2 subunit and nicotine treatment affected the expression levels of the adipokine genes Tnfα, Cox2 and AdipoQ in WAT and of AdipoQ in BAT. Finally, analysis of a cellular model of cultured adipocytes demonstrated that application of nicotine after silencing of the β2 nAChR subunit significantly elevated the expression level of Cox2 gene. Together, our data suggest a molecular link between the β2 nACh receptor subunit and the expression levels of specific adipokines, which is also affected by nicotine.
authors.affiliation: The Genetic Institute, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Alona
authors.initials: A
authors.lastname: Gochberg-Sarver
authors.forename: Merav
authors.initials: M
authors.lastname: Kedmi
authors.forename: Mali
authors.initials: M
authors.lastname: Gana-Weisz
authors.forename: Anat
authors.initials: A
authors.lastname: Bar-Shira
authors.forename: Avi
authors.initials: A
authors.lastname: Orr-Urtreger
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D052242:Adiponectin; D051546:Cyclooxygenase 2; D009538:Nicotine; D034741:RNA, Small Interfering; D011978:Receptors, Nicotinic; D014409:Tumor Necrosis Factor-alpha; C499919:Adipoq protein, mouse; C077623:Ptgs2 protein, mouse