Overfeeding-induced obesity in spontaneously hypertensive rats: an animal model of the human metabolic syndrome.
OBJECTIVE
The metabolic syndrome (MS) has become an epidemiological problem in Western countries. We developed a diet-induced obese rat model that mimics all the symptoms of MS in humans, but whose insulin resistance, hyperphagia and hyperleptinemia are caused by nutrition rather than genetic modifications.


METHODS
Spontaneously hypertensive rats (SHR) were allowed for 12 weeks to choose between a cafeteria diet (CD, 20.3 kJ/g) and standard rat chow (11.7 kJ/g). Controls received rat chow.


RESULTS
Body weight (BW) exceeded control levels when SHR were fed with CD. The increase in BW was attributed to enhanced energy intake. The abundance of abdominal fat as well as the plasma levels of leptin and triglycerides increased concomitant with glucose, insulin and C-peptide. This prediabetic condition was further confirmed by a markedly increased insulin response following glucose challenge and by impaired glucose utilization after insulin tolerance tests.


CONCLUSIONS
Increases in food intake and BW despite hyperleptinemia indicate leptin resistance following CD feeding. CD-fed SHR feature leptin and insulin resistance, hypertension and obesity, thus mimicking the situation of MS patients. As such, our model is more suitable than the genetically modified rat models used to study human MS.
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
Anja
A
Miesel
Helge
H
Müller
Margot
M
Thermann
Marc
M
Heidbreder
Peter
P
Dominiak
Walter
W
Raasch
D050153:Abdominal Fat; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose; D001794:Blood Pressure; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D004032:Diet / Q000009:adverse effects / Q000379:methods; D004195:Disease Models, Animal; D002149:Energy Intake; D006339:Heart Rate; D006963:Hyperphagia / Q000097:blood / Q000150:complications*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology*; D009765:Obesity / Q000097:blood / Q000209:etiology*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D020738:Leptin; D014280:Triglycerides