Sensitivity to the satiating effects of exendin 4 is decreased in obesity-prone Osborne-Mendel rats compared to obesity-resistant S5B/Pl rats.
BACKGROUND
Osborne-Mendel (OM) rats are prone to obesity when fed a high-fat diet, whereas S5B/Pl (S5B) rats are resistant to diet-induced obesity when fed the same diet. OM rats have a decreased satiation response to fatty acids infused in the gastrointestinal tract, compared to S5B rats. One possible explanation is that OM rats are less sensitive to the satiating hormone, glucagon-like peptide 1 (GLP-1). GLP-1 is produced in the small intestine and is released in response to a meal. The current experiments examined the role of GLP-1 in OM and S5B rats.


METHODS
Experiment 1 examined preproglucagon mRNA expression in the ileum of OM and S5B rats fed a high-fat (55% kcal) or low-fat (10% kcal) diet. Experiment 2 investigated the effects of a 2 h high-fat meal after a 24 h fast in OM and S5B rats on circulating GLP-1 (active) levels. Experiment 3 examined the effects of exendin-4 (GLP-1 receptor agonist) administration on the intake of a high-fat or a low-fat diet in OM and S5B rats.


RESULTS
Preproglucagon mRNA levels were increased in the ileum of OM rats compared to S5B rats and were increased by high-fat diet in OM and S5B rats. OM and S5B rats exhibited a similar meal-initiated increase in circulating GLP-1 (active) levels. Exendin-4 dose dependently decreased food intake to a greater extent in S5B rats compared to OM rats. The intake of low-fat diet, compared to the intake of high-fat diet, was more sensitive to the effects of exendin-4 in these strains.


CONCLUSIONS
These results suggest that though OM and S5B rats have similar preproglucagon mRNA expression in the ileum and circulating GLP-1 levels, OM rats are less sensitive to the satiating effects of GLP-1. Therefore, dysregulation of the GLP-1 system may be a mechanism through which OM rats overeat and gain weight.
Primeaux
S D
SD
Dietary Obesity Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA. Stefany.Primeaux@pbrc.edu
Barnes
M J
MJ
Braymer
H D
HD
Bray
G A
GA
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage*; D002149:Energy Intake / Q000235:genetics / Q000502:physiology; D000077270:Exenatide; D005786:Gene Expression Regulation / Q000235:genetics; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D052336:Proglucagon / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012527:Satiation / Q000502:physiology*; D014688:Venoms / Q000235:genetics / Q000378:metabolism*; D015430:Weight Gain / Q000502:physiology
D004041:Dietary Fats; D010455:Peptides; D012333:RNA, Messenger; D014688:Venoms; D052336:Proglucagon; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide
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