E6. Hypothalamic BMAL1-knockout cell lines for the study of circadian feeding regulation

You may find interesting:

E9. The effect of resveratrol on reducing neointimal growth after femoral artery injury is abolished in AMPKα2 knock-out mice

Liwei Zhou, June Guo, Hangjun Zhang, Scott Heximer, Adria Giacca

Posted by on January 1, 2018

Poster_session_1 Endo

C8. Cardioprotective benefits of combined treatment with glucagon-like peptide-1 receptor agonist and sodium glucose transporter 2 inhibitor in mice

Dorrin Zarrin Khat, Abdul Momen, Muhammad A. Siraj, Sina Hadipour-Lakmehsari, Mark J. Chandy, Mansoor Husain

Posted by on January 1, 2018

Poster_session_2 Cardio

Poster Session 2 - E6

1Matthew N. Clemenzi, 1Erika K. Tse, 1Jennifer A. Chalmers, 1Neruja Loganathan, 1Ashkan Salehi, 1Alexandre Martchenko, 1,2Patricia L. Brubaker, 1,2,3Denise D. Belsham

1 Dept. of Physiology, University of Toronto; 2 Dept. of Medicine, University of Toronto; 3 Dept. of Obstetrics and Gynaecology, University of Toronto

Circadian rhythms drive the timing of daily physiological functions, including food intake. These rhythms depend on core clock genes, including BMAL1. Disruptions of the molecular clock in rodents have been shown to induce obesity and metabolic syndrome. We hypothesize that clock genes, specifically BMAL1, contributes to central energy homeostasis by altering the expression of feeding-related neuropeptides. We have previously demonstrated the rhythmic expression of neuropeptides in clonal neuropeptide Y (NPY)/agouti-related peptide (AgRP)-expressing cells. BMAL1 is hypothesized to play a role in neuropeptide gene expression; thus, hypothalamic cell lines were derived from adult BMAL1-wildtype or knockout (KO) C57BL/6J mice. Hypothalamic primary cultures were immortalized with SV40 T-antigen. Characterization of the mixed neuronal cell line demonstrated a robust expression of several neuropeptides, and the mixed line is currently being subcloned to obtain clonal neuronal cell lines. Our recent results show that bisphenol A (BPA), an endocrine disrupting chemical, alters proopiomelanocortin (POMC) and clock mRNA levels in POMC-expressing neurons. However, preliminary results indicate that BPA-mediated increases in POMC mRNA are not changed in BMAL1-KO cells, suggesting that BMAL1 may not be involved in the control of POMC by BPA. However, endogenous expression of NPY, AgRP, and POMC in the BMAL1-KO line appears to differ significantly from those in the wild-type cell line, suggesting a role for BMAL1 in regulating the basal expression of these neuropeptides. The newly-generated cell lines will serve as models of hypothalamic circadian disruption and will be valuable to define the roles of BMAL1 in specific hypothalamic neurons.