Research

 

Research Goals

Obesity, diabetes and the metabolic syndrome: Our research goals are to understand the signaling from the intestine and fat cells as the largest endocrine organs and the interaction with the central (CNS) and enteric nervous system (ENS) (see Fig/Kuva 1. Heinonen M, Purhonen AK, Herzig KH. Adipokiinit - rasvakudoksen viestinviejistä valoa lihavuuden haittojen ymmärtämiseen. Duodecim 2006;122: 2177-8).

adipokines

Peptides released from these organs have been attributed to be involved in various diseases like obesity, diabetes and the metabolic syndrome. New, very promising peptides have recently been discovered: ghrelin, orexin, apelin visfatin and ACBP/DBI. We utilized transgene technology to establish useful models to investigate the function of these peptides in an integrative approach. We started to establish transgenic animal colonies with overexpression or knockout of several of these peptides developing models for therapeutic targeting.

Additional Areas of Interest

Pathophysiology of acute and chronic pancreatitis: Acute pancreatitis with infected necrosis is still a tremendous clinical problem with significant mortality in which our current therapy is only directed against it complications (see also innate immunity). Its pathophysiology is far from being understood. Trypsin is the key molecule in the pathophysiological process. Mutations in the trypsinogen and trypspin inhibitor gene have been detected to correlate with the disease. We are analyzing families with such mutations. In addition, depletion of spermidine and spermine results in an activation of trypsinogen which can be prevented or ameliorated by treatment with bismethylspermine in various pancreatitis models (cooperation with Leena Alhonen and Isto Nordback).

Innate Immunity: The intestinal mucosal cells are key players in the antimicrobial defense secreting peptides with antimicrobial activities (Otte et al. 2003): A single layer of epithelial cells in the human digestive tract depicts really the line between live and death! The intestinal cell with its numerous interactions with the luminal contents are at the center of the production of various substances preventing infection. We investigate the expression of these peptides in disease like inflammation in the intestine (inflammatory bowel disease, pouchitis, celiac disease, pancreatitis) and its interaction with the bacterial environment.

Exercise Metabolism: Acute exercise and regular physical activity modulate many physiological functions, including lipids and glucose metabolism in skeletal muscles, adipocytes and other various cells.  The regulation of these energy substrates via body movements provide a strong a positive strategy in preventing and managing metabolic disturbances including obesity and diabetes.  From rodent and human models, our group in interested in investigating various exercise modalities and conditions on neuroendocrine functions, peptides release, cytokines release and expression and immune responses as modulating elements of metabolic dysfunctions. 

 

Methods

Using transgene technology we establish animal models to elucidate the effects of regulatory peptides on metabolism and communication between organs involved in its regulation. Our investigations are in humans, on the animal level, on isolated organs as well as on the cellular level.

We analyze metabolic performance/energy expenditure in home cages (for mice and rats) as well as physical activity, drinking and feeding behaviour (TSE LabMaster System®) in environmental controlled chamber in different temperatures (+4° - +32°) as well as oxygen contents. The calorimetry components are operated as an open circuit measuring system for determining parameters like O2-consumption, CO2-production, respiratory exchange rate (RER) and heat. The activity measurements are measured via infrared sensors. In cooperation with the MRI group whole body fat is determined. Peptide determinations are performed by ELISA and RIA systems.

We make diagnostics for helicobacter pylori, for enzyme deficiencies, for liver- and pancreas-functions, for gastric motilities and for nutrition control, non-invasively, using 13C-stable isotope breath tests on IRIS® (Wagner Analysen Technik GmbH).

Bio-Plex 200 (Bio-Rad Laboratories Inc) is a system based to a Luminex xMAP technology that allows analysis of up to 100 biomolecules in single well. Thus we are able to measure concentrations of several peptides, cytokines and adipokines etc. in a small sample volume (µl) simultaneously. We have established analyses for humans, mice and rats.

Collaboration

University of Oulu and OYS:

Biocenter of Oulu:  Markku Savolainen (Clinical Research Center/SALVE consortium), Marjo-Riitta Järvelin (KTL), Mika Ala-Korpela (SALVE), Kalervo Hiltunen (Dept. of Biochemistry),

OYS and other Faculties: Laure Morin-Papunen, Juha Tapanainen (Dept. of Obstetrics and Gynaecology, Juha Saarnio (Dept of Surgery), Timo Jämsä (Dept. of Medical Technology), Sirkka Keinänen-Kiukaanniemi (KTL), Hannu Rintamäki (TTL), Tuula Salo (Dept. of Dentistry), Esa Hohtola and Seppo Saarela (Dept. of Biology).

 

Finland:

Pekka Miettinen, Imre Ilves, Hannu Paajanen, Leo Niskanen, Soili Lehto, Heimo Viinamäki (Kuopio Univ. Hospital, Univ. Kuopio), Matti Uusitupa, Carsten Carlberg, Vesa-Pekka Lehto, Leila Karhunen, Kristiina Järvinen, Kaisa Poutanen (VTT/University of Eastern Finland), Matti Airaksinen, Jari Rossi, (Neuroscience Center, Univ. Helsinki), Isto Nordback (Univ. Tampere), Tarja Stenberg and Karl Åkerman (Institute of Biomedicine/Physiology, Biomedicum, Univ. Helsinki), Jarno Salonen (University of Turku), Prof. Johanna Buchert (VTT Helsinki), Eriika Savontaus (Univ of Turku).

International:

Andreas Susenbeth (Univ. Kiel, Germany), Jürgen Eckel (Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Heinrich-Heine-University Düsseldorf, Germany), Enrique Rodilla & Jose Maria Pascual (Hypertension Clinics, Sagunto Hospital, University of Valencia, Valencia, Spain), Christoph Beglinger (Univ. Basel, Switzerland), Takeshi Sakurai (Univ. Tsukuba, Ibaraki, Japan), Gunnar Flemström (Univ. Uppsala, Sweden), Jarek Walkowiak (Univ. Poznan, Poland), Krystyna Koziec (University of Agriculture in Krakow; Poland), Hans-Rudolf Berthoud, Neurobiology of Nutrition Laboratory Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, USA, Sysdiet consortium (link), Takayuki Naito, Kanagawa University, Japan.

 

Member of the COST action BM602 - Meeting Adipose Tissue: A Key Target for Prevention of the Metabolic Syndrome

Member of the FA COST action FA1005 "Improving Health Properties of Food by Sharinf our Knowledge on the Digestive Process (INFOGEST)"

 

Financial Support

Finnish Academy, Novo Nordisk Foundation, Suomen Kulttuurirahasto, Orion-säätiö, Suomen diabetessäätiö.