Browsing by Subject "pharmacotherapy"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Mechanisms of the pro-lipolytic and anti-obesity effects of the VGF-derived peptide TLQP-21
    (2015-10) Cero, Cheryl
    Obesity is a major public health problem; in the U.S. nearly one third of the population is obese. The adipose tissue is innervated by the sympathetic nervous system (SNS), which regulates fat mass by playing a key role in initiating lipolysis and regulating lipid mobilization. TLQP-21, a 21 amino acid peptide encoded by the pre-pro-peptide VGF (non acronymic) expressed in the brain and sympathetic neurons innervating the adipose organ. Complement 3a receptor 1, C3aR1, is the target receptor for TLQP-21. Based on previous finding where peripheral TLQP-21 decreases adipocyte diameter and enhance β-adrenergic receptors (β-ARs) lipolysis in adipocytes the hypothesis tested in my thesis is that C3aR1 and β-ARs are required for TLQP-21 anti-obesity effects and the pro-lipolytic effects are mediated by increased mobilization of [Ca2+]i. Departing from the first experimental structural analysis of TLQP-21 in solution and receptor-bound state, we tested our hypothesis using a combined in vitro and in vivo approach. Using 3T3L1 cells and pre-adipocytes as our in vitro model, we determined that TLQP-21 enhances lipolysis via increased intracellular Ca2+ concentration [Ca2+]i, and activation of the MAPK/ERK pathway. The physiological effects of TLQP-21 were investigated in vivo using wild type, β-less (β1, β2, β3-AR KO) and C3aR1 KO mice. Chronic TLQP-21 treatment in obese wild type mice significantly decreased body weight and fat mass promoting an overall healthier metabolic phenotype. Conversely β-less and C3aR1 KO resulted fully resistant to the anti-obesity effects. Herein we identified the mechanism of TLQP-21 pro-lipolytic and anti-obesity effect and could thus be regarded as a novel target for pharmacotherapies of obesity.
  • Thumbnail Image
    Item
    A Student-Initiated, Integrated Pharmacotherapeutics Learner-Centered Course
    (University of Minnesota, College of Pharmacy, 2015) Hopman, Shawn; Popovich, Nicholas G.
    Objective: To evaluate a learner-centered, elective course complementing pharmacotherapeutic instruction. Design: A one credit-hour elective as developed. Enrolled students were responsible for article selection and to lead in-class discussions. A content-validated discussant rubric was use to peer review each discussant. Assessment: Enrolled students kept current on the literature and nurtured an obligation to themselves and their peers to be prepared on a weekly basis to discuss the selected article. Discussion demonstrated varied opinions and provided ample opportunity for students to use technical/clinical language. Also, the course allowed for thinking at a higher level, discussing complex ideas/issues, and developing oral communication skills. Conclusions: This learner-centered approach allowed the enrolled students to take ownership of their learning and complement their learning from the traditional mode of learning in two pharmacotherapeutic courses. It encouraged the students to investigate the clinical literature as a means to complement and enhance their knowledge.