Institute of Biomedicine, University of Turku
The goal of the project
Obesity with related metabolic and cardiovascular diseases is an increasing problem, but current pharmacotherapies for obesity are clearly insufficient. Neuropeptides NPY (neuropeptide Y) and POMC (melanocortins) play key roles in regulation of body weight. There is plenty of evidence both in experimental animals and in humans that overactive NPY system and inactive melanocortin system will lead to obesity. Therefore, these neuropeptides are attractive targets for anti-obesity drug development. Our aim is to understand tissue-specific mechanisms of NPY and melanocortin action in order to facilitate drug development for metabolic diseases and cardiovascular diseases. We use transgenic mouse models and viral gene delivery combined with pharmacological and dietary interventions. The effects of interventions on body weight and composition, feeding and activity behavior, white and brown adipose tissue morphology and function, glucose and lipid metabolism and obesity biomarkers are studied. The cardiovascular parameters are measured with telemetric method (blood pressure and heart rate), echocardiography and micromyography. Recently, we have started a novel project to understand the impact of the genetics and epigenetics of these genes on the risk of cardiometabolic diseases and whether the epigenetic inheritance of metabolic diseases could be prevented.
Eerola K, Virtanen S, Vähätalo L, Ailanen L, Cai M, Hruby V, Savontaus M, Savontaus E. Hypothalamic γ-melanocyte stimulating hormone gene delivery reduces fat mass in male mice. J Endocrinol. 2018 Oct 1;239(1):19–31.
Ailanen L, Vähätalo LH, Salomäki-Myftari H, Mäkelä S, Orpana W, Ruohonen ST, Savontaus E. Peripherally Administered Y2-Receptor Antagonist BIIE0246 Prevents Diet-Induced Obesity in Mice With Excess Neuropeptide Y, but Enhances Obesity in Control Mice. Front Pharmacol. 2018 Apr 5;9:319.
Ailanen L, Ruohonen ST, Vähätalo LH, Tuomainen K, Eerola K, Salomäki-Myftari H, Röyttä M, Laiho A, Ahotupa M, Gylling H, Savontaus E. The metabolic syndrome in mice overexpressing neuropeptide Y in noradrenergic neurons. J Endocrinol. 2017 Jul;234(1):57-72.
Vähätalo L, Ruohonen ST, Kovalainen M, Huotari H, Mäkelä K, Määttä JA, Mäkelä S, Ailanen S, Ruohonen S, Röyttä M, Herzig KH, Savontaus E: Neuropeptide Y in the noradrenergic neurones induces obesity and inhibits sympathetic tone. Acta Physiol (Oxf). 2015 Apr;213(4):902-19. doi: 10.1111/apha.12436. Epub 2014 Dec 26
Eerola K, Rinne P, Penttinen AM, Vähätalo L, Savontaus M, Savontaus E: α-MSH overexpression in nucleus tractus solitaries decreases fat mass and elevates heart rate, J Endocrinol, 2014 Jul;222(1):123-36. doi: 10.1530/JOE-14-0064
Rinne P, Nordlund W, Heinonen I, Penttinen AM, Saraste A, Ruohonen ST, Mäkelä S, Vähätalo L, Kaipio K, Cai M, Hruby VJ, Ruohonen S, Savontaus E: α-Melanocyte-stimulating hormone regulates vascular NO availability and protects against endothelial dysfunction. Cardiovasc Res. 97:360-368, 2013
Ruohonen S, Pesonen U, Moriz N, Kaipio K, Röyttä M, Koulu M, Savontaus E. Transgenic mice overexpressing neuropeptide Y in noradrenergic neurons: A novel model of increased adiposity and impaired glucose tolerance. Diabetes, 57(6):1517-25, 2008.
Eriika Savontaus, MD, PhD
Assistant Professor of Pharmacology and Therapeutics