Organization

Institute of Biomedicine (Department of Pharmacology, Drug Development and Therapeutics), University of Turku

Research Group

Petteri Rinne, PhD; Laura Vähätalo, PhD;  Liisa Ailanen, MSc

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.

Publications:

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

Vähätalo LH, Ruohonen ST, Mäkelä S, Ailanen L, Penttinen AM, Stormi T, Kauko T, Piscitelli F, Silvestri C, Savontaus E and Di Marzo V: Role of endocannabinoid system in obesity induced by neuropeptide Y overexpression in noradrenergic neurons and sympathetic nervous system. Nutr Diabetes. 2015 Apr 27;5:e151. doi: 10.1038/nutd.2015.1

Rinne P, Ahola-Olli A, Nuutinen S, Koskinen E, Eerola K, Juonala M, Kähönen M, Lehtimäki T, Raitakari OT, and Savontaus E: Deficiency in Melanocortin 1 Receptor Signaling Predisposes to Vascular Endothelial Dysfunction and Increased Arterial Stiffness in Mice and Humans. Arterioscler Thromb Vasc Biol 2015 Jul;35(7):1678-86. pii: ATVBAHA.114.305064

Heinonen I, Rinne P, Ruohonen ST, Ruohonen S, Ahotupa M, Savontaus E:The effects of equal caloric high fat and western diet on metabolic syndrome, oxidative stress, and vascular endothelial function in mice. Acta Physiologica, Acta Physiol (Oxf). 2014 Jul;211(3):515-27. doi: 10.1111/apha.12253

Rinne PP,  Ståhle M, Hellberg S, Silvola J, Salomäki H, Koskinen E, Nuutinen S, Saraste A, Roivainen A and Savontaus E: Pharmacological Activation of the Melanocortin System Limits Plaque Inflammation and Ameliorates Vascular Dysfunction in Atherosclerotic Mice. Arterioscler Thromb Vasc Biol. 2014 Jul;34(7):1346-54. doi: 10.1161/ATVBAHA.113.302963

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

Eerola K, Nordlund W, Virtanen S, Dickens A, Mattila M, Ruohonen ST, Chua SC Jr, Wardlaw SL, Savontaus M and Savontaus E: Lentivirus mediated α-melanocyte stimulating hormone overexpression in the hypothalamus decreases diet induced obesity in mice, J Neuroendocrinol. 25: 1298–1307, 2013

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

Rinne P, Harju J, Mäkelä S, Savontaus E: Genetic and pharmacologic mouse models of chronic melanocortin activation show enhanced baroreflex control of heart rate, Regul Pept. 182:19-27, 2013

Rinne P, Penttinen AM, Nordlund W, Ahotupa M, Savontaus E: α-MSH Analogue Attenuates Blood Pressure Elevation in DOCA-Salt Hypertensive Mice. PLoS One 8(8):e72857, 2013.

Ruohonen ST, Savontaus E, Rinne P, Rosmaninho-Salgado J, Cavadas C, Ruskoaho H, Koulu M, Pesonen U Stress-Induced Hypertension and Increased Sympathetic Activity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons. Neuroendocrinology, 89(3):351-360, 2009.

Ruohonen ST, Abe K, Kero M, Toukola L, Ruohonen S, Röyttä M, Koulu M, Pesonen U, Zukowska Z, Savontaus E Sympathetic nervous system-targeted neuropeptide Y overexpression in mice enhances neointimal formation in response to vascular injury. Peptides 30:715-720, 2009.

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.

Principal Investigator
Eriika Savontaus, MD, PhD
Adjunct Professor of Pharmacology
Clinical lecturer in Clinical Pharmacology

eriika.savontaus(at)utu.fi

Eriika Savontaus
Neuroendocrine mechanisms in  pathogenesis and therapeutics of metabolic and cardiovascular diseases