Neuroendocrine mechanisms in pathogenesis and therapeutics of cardiometabolic diseases

​Description of Research

Obesity with associated metabolic and cardiovascular diseases is an increasing problem, but current pharmacotherapies for obesity are clearly insufficient. Neuropeptides NPY (neuropepti-de 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 met-abolic and cardiovascular diseases. We use genetic mouse models and viral gene delivery combined with pharmacological and dietary interventions in disease models of obesity, im-paired glucose tolerance, atherosclerosis and heart failure. The effects of interventions on body weight and composition, feeding and energy expenditure, 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.

Members of the research group

PhD Petteri Rinne
MSc, MSc (Tech) Liisa Ailanen
MSc Laura Vähätalo
MSc Minttu Mattila
Students Salla Nuutinen, Salla Juhantalo
Laboratory Technician Sanna Bastman

Selected Publications

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 Apr 30. pii: ATVBAHA.114.305064 IF 6.008

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. IF 4.382

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. Arte-rioscler Thromb Vasc Biol. 2014 Jul;34(7):1346-54. IF 6.008

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 IF 5.940

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. 8.474