Abstract
Background:Exenatide (exendin-4) is an incretin mimetic currently marketed as an antidiabetic agent for patients with type 2 diabetes. In preclinical models, a reduction in body weight has also been shown in low-fat-fed, leptin receptor-deficient rodents.Objective:To more closely model the polygenic and environmental state of human obesity, we characterized the effect of exenatide on food intake and body weight in high-fat-fed, normal (those with an intact leptin signaling system) rodents. As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity.Methods and results:High-fat-fed C57BL/6 mice and Sprague-Dawley rats were treated with exenatide (3, 10 and 30 μg/kg/day) for 4 weeks via subcutaneously implanted osmotic pumps. Food intake and body weight were assessed weekly. At 4 weeks, body composition and plasma metabolic profiles were measured. Kaolin consumption and locomotor activity were measured in fasted Sprague-Dawley rats following a single intraperitoneal injection of exenatide (0.1-10 μg/kg). Exenatide treatment in mice and rats dose-dependently decreased food intake and body weight; significant reductions in body weight gain were observed throughout treatment at 10 and 30 μg/kg/day (P<0.05). Decreased body weight gain was associated with a significant decrease in fat mass (P<0.05) with sparing of lean tissue. Plasma cholesterol, triglycerides and insulin were also significantly reduced (P<0.05). Exenatide at 10 μg/kg significantly reduced food intake (P<0.05) but failed to induce kaolin intake. In general, locomotor activity was reduced at doses of exenatide that decreased food intake, although a slightly higher dose was required to produce significant changes in activity.Conclusion:Systemic exenatide reduces body weight gain in normal, high-fat-fed rodents, a model that parallels human genetic variation and food consumption patterns, and may play a role in metabolic pathways mediating food intake.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1332-1340 |
| Number of pages | 9 |
| Journal | International Journal of Obesity |
| Volume | 30 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 21 2006 |
| Externally published | Yes |
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Keywords
- Body composition
- High fat diet
- Kaolin consumption
- Locomotor activity
- Metabolites
- Type 2 diabetes
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Public Health, Environmental and Occupational Health
- Endocrinology
- Food Science
- Endocrinology, Diabetes and Metabolism
Cite this
Antiobesity action of peripheral exenatide (exendin-4) in rodents : Effects on food intake, body weight, metabolic status and side-effect measures. / Mack, C. M.; Moore, C. X.; Jodka, C. M.; Bhavsar, S.; Wilson, J. K.; Hoyt, J. A.; Roan, J. L.; Vu, C.; Laugero, K. D.; Parkes, D. G.; Young, A. A.
In: International Journal of Obesity, Vol. 30, No. 9, 21.09.2006, p. 1332-1340.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antiobesity action of peripheral exenatide (exendin-4) in rodents
T2 - Effects on food intake, body weight, metabolic status and side-effect measures
AU - Mack, C. M.
AU - Moore, C. X.
AU - Jodka, C. M.
AU - Bhavsar, S.
AU - Wilson, J. K.
AU - Hoyt, J. A.
AU - Roan, J. L.
AU - Vu, C.
AU - Laugero, K. D.
AU - Parkes, D. G.
AU - Young, A. A.
PY - 2006/9/21
Y1 - 2006/9/21
N2 - Background:Exenatide (exendin-4) is an incretin mimetic currently marketed as an antidiabetic agent for patients with type 2 diabetes. In preclinical models, a reduction in body weight has also been shown in low-fat-fed, leptin receptor-deficient rodents.Objective:To more closely model the polygenic and environmental state of human obesity, we characterized the effect of exenatide on food intake and body weight in high-fat-fed, normal (those with an intact leptin signaling system) rodents. As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity.Methods and results:High-fat-fed C57BL/6 mice and Sprague-Dawley rats were treated with exenatide (3, 10 and 30 μg/kg/day) for 4 weeks via subcutaneously implanted osmotic pumps. Food intake and body weight were assessed weekly. At 4 weeks, body composition and plasma metabolic profiles were measured. Kaolin consumption and locomotor activity were measured in fasted Sprague-Dawley rats following a single intraperitoneal injection of exenatide (0.1-10 μg/kg). Exenatide treatment in mice and rats dose-dependently decreased food intake and body weight; significant reductions in body weight gain were observed throughout treatment at 10 and 30 μg/kg/day (P<0.05). Decreased body weight gain was associated with a significant decrease in fat mass (P<0.05) with sparing of lean tissue. Plasma cholesterol, triglycerides and insulin were also significantly reduced (P<0.05). Exenatide at 10 μg/kg significantly reduced food intake (P<0.05) but failed to induce kaolin intake. In general, locomotor activity was reduced at doses of exenatide that decreased food intake, although a slightly higher dose was required to produce significant changes in activity.Conclusion:Systemic exenatide reduces body weight gain in normal, high-fat-fed rodents, a model that parallels human genetic variation and food consumption patterns, and may play a role in metabolic pathways mediating food intake.
AB - Background:Exenatide (exendin-4) is an incretin mimetic currently marketed as an antidiabetic agent for patients with type 2 diabetes. In preclinical models, a reduction in body weight has also been shown in low-fat-fed, leptin receptor-deficient rodents.Objective:To more closely model the polygenic and environmental state of human obesity, we characterized the effect of exenatide on food intake and body weight in high-fat-fed, normal (those with an intact leptin signaling system) rodents. As glucagon-like peptide-1 receptor agonism has been found to elicit behaviors associated with visceral illness in rodents, we also examined the effect of peripheral exenatide on kaolin consumption and locomotor activity.Methods and results:High-fat-fed C57BL/6 mice and Sprague-Dawley rats were treated with exenatide (3, 10 and 30 μg/kg/day) for 4 weeks via subcutaneously implanted osmotic pumps. Food intake and body weight were assessed weekly. At 4 weeks, body composition and plasma metabolic profiles were measured. Kaolin consumption and locomotor activity were measured in fasted Sprague-Dawley rats following a single intraperitoneal injection of exenatide (0.1-10 μg/kg). Exenatide treatment in mice and rats dose-dependently decreased food intake and body weight; significant reductions in body weight gain were observed throughout treatment at 10 and 30 μg/kg/day (P<0.05). Decreased body weight gain was associated with a significant decrease in fat mass (P<0.05) with sparing of lean tissue. Plasma cholesterol, triglycerides and insulin were also significantly reduced (P<0.05). Exenatide at 10 μg/kg significantly reduced food intake (P<0.05) but failed to induce kaolin intake. In general, locomotor activity was reduced at doses of exenatide that decreased food intake, although a slightly higher dose was required to produce significant changes in activity.Conclusion:Systemic exenatide reduces body weight gain in normal, high-fat-fed rodents, a model that parallels human genetic variation and food consumption patterns, and may play a role in metabolic pathways mediating food intake.
KW - Body composition
KW - High fat diet
KW - Kaolin consumption
KW - Locomotor activity
KW - Metabolites
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=33748118597&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33748118597&partnerID=8YFLogxK
U2 - 10.1038/sj.ijo.0803284
DO - 10.1038/sj.ijo.0803284
M3 - Article
C2 - 16534527
AN - SCOPUS:33748118597
VL - 30
SP - 1332
EP - 1340
JO - International Journal of Obesity
JF - International Journal of Obesity
SN - 0307-0565
IS - 9
ER -