Differential secretion of satiety hormones with progression of obesity in JCR:LA-corpulent rats.
OBJECTIVE
To characterize the gastrointestinal tract at the onset and in well-established obesity.


METHODS
Lean (+/?) and obese (cp/cp) male JCR:LA-cp rats lacking a functional leptin receptor were killed at 3.5 weeks and 9 months of age and plasma concentrations of satiety hormones determined. The small intestine, colon, and stomach were measured, weighed, and mRNA levels of satiety genes quantified.


RESULTS
At the onset of obesity, obese rats had greater intestine, colon, and liver mass when adjusted for body weight compared to lean rats. Conversely, adult rats with established obesity had lower intestine and colon mass and length after adjustment for body weight. Early changes in gene expression included decreased ghrelin mRNA levels in stomach and increased peptide YY (PYY) mRNA levels in duodenum of young obese rats. After massive accumulation of adipose tissue had occurred, adult obese rats had increased proglucagon and ghrelin mRNA expression in the proximal intestine. In the distal small intestine, obese rats had lower proglucagon, ghrelin, and PYY mRNA levels. Finally, at the onset and in well-established obesity, obese rats had higher plasma insulin, amylin, glucagon like peptide-1 (GLP-1), and PYY, a finding, with the exception of insulin, unique to this model. Plasma total ghrelin levels were significantly lower at the onset of obesity and established obesity compared to the lean rats.


CONCLUSIONS
Several defects are manifested in the obese gut early on in the disease before the accumulation of large excesses of body fat and represent potential targets for early intervention in obesity.
Parnell
Jill A
JA
Department of Medical Sciences, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Reimer
Raylene A
RA
D000682:Amyloid / Q000097:blood / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D003106:Colon / Q000196:embryology / Q000473:pathology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D054439:Ghrelin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007421:Intestine, Small / Q000196:embryology / Q000473:pathology; D058228:Islet Amyloid Polypeptide; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D019894:Peptide YY / Q000097:blood / Q000235:genetics / Q000378:metabolism; D052336:Proglucagon / Q000097:blood / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012528:Satiety Response / Q000502:physiology*; D013270:Stomach / Q000473:pathology
D000682:Amyloid; D005768:Gastrointestinal Hormones; D054439:Ghrelin; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D019894:Peptide YY; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1