Sarcopenia in the aging high-fat fed rat: a pilot study for modeling sarcopenic obesity in rodents.
Obesity has been suggested as a risk factor for sarcopenia. However, the underlying pathogenic concept of sarcopenic obesity is mainly based on phenotypical data from clinical observation. The present pilot study describes a rodent animal model which opens up prospects to carry out translational research of sarcopenic obesity in an experimental setting. Starting with 2 months, male Wistar rats were fed with a diet containing either 25 en % (control diet, CD) versus 45 en % (high fat diet, HFD) of neutral fat. At the age of 20 and 23 months quadriceps muscles were examined in vivo by magnetic resonance techniques which revealed a positive correlation between muscular fat and body weight (r = 0.639) and a negative correlation between muscular fat content and muscle volume (r = -0.742). Expression and phosphorylation status of proteins within the PKB/Akt and AMPK-dependent signaling pathway were examined in muscles of the 24 month-old animals which significantly showed a 50 percent upregulation of Ser(473)P-PKB/Akt and a 90 % constitutive downregulation of S6K1 in the HFD rats. Notably, S6K1 is a key mediator for muscular protein biosynthesis with additional negative feedback on PKB/Akt. Furthermore, muscular expression of the mitochondrial key regulator PGC-1α in the aged HFD rats was only 25 % of that concurrent controls (p = 0.029). These explorative findings in the aging high-fat fed rat might serve as a firm starting point for controlled longitudinal observations in a larger animal cohort of both sexes studying the natural history of sarcopenic obesity.
Institute for Biomedicine of Aging, Friedrich-Alexander-Universität Erlangen-Nürnberg, Heimerichstrasse 58, 90419 Nuremberg, Germany. cornelius.bollheimer@iba.fau.de
L Cornelius
LC
Bollheimer
Roland
R
Buettner
Georg
G
Pongratz
Rita
R
Brunner-Ploss
Christine
C
Hechtl
Miriam
M
Banas
Katrin
K
Singler
Okka W
OW
Hamer
Christian
C
Stroszczynski
Cornel C
CC
Sieber
Claudia
C
Fellner
D064413:3-Phosphoinositide-Dependent Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D059305:Diet, High-Fat / Q000009:adverse effects*; D004041:Dietary Fats / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009765:Obesity / Q000150:complications / Q000378:metabolism; D009929:Organ Size; D010766:Phosphorylation; D010865:Pilot Projects; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D055948:Sarcopenia / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction; D057170:Translational Research, Biomedical
D004041:Dietary Fats; D011494:Protein Kinases; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D000091162:AMP-Activated Protein Kinase Kinases