Peptides that Regulate Food Intake: Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285-0545 Agonists to opioid receptors induce a positive energy balance, whereas antagonists at these receptors reduce food intake and body weight in rodent models of obesity. An analog of 3,4-dimethyl-4-(3-hydroxyphenyl)pip...
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Published in | American journal of physiology. Regulatory, integrative and comparative physiology Vol. 284; no. 6; pp. 1399 - R1408 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.06.2003
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Subjects | |
Online Access | Get full text |
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Summary: | Lilly Research Laboratories, Lilly Corporate Center,
Indianapolis, Indiana 46285-0545
Agonists to opioid receptors
induce a positive energy balance, whereas antagonists at these
receptors reduce food intake and body weight in rodent models of
obesity. An analog of 3,4-dimethyl-4-(3-hydroxyphenyl)piperidine, LY255582, is a potent non-morphinan antagonist for µ-, -, and -receptors ( K i of 0.4, 2.0, and 5.2 nM,
respectively). In the present study, we examined the effects of oral
LY255582 treatment on caloric intake, calorie expenditure, and body
composition in dietary-induced obese rats. Acute oral treatment of
LY255582 produced a dose-dependent decrease in energy intake and
respiratory quotient (RQ), which correlated with the occupancy of
central opioid receptors. Animals receiving chronic oral treatment with
LY255582 for 14 days maintained a negative energy balance that was
sustained by increased lipid use. Analysis of body composition revealed
a reduction in fat mass accretion, with no change in lean body mass, in
animals treated with LY255582. Therefore, chronic treatment with
LY255582 reduces adipose tissue mass by reducing energy intake and
stimulating lipid use.
respiratory quotient; body composition; dual-energy X-ray
absorptiometry; indirect calorimetry; ex vivo receptor binding |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0363-6119 1522-1490 |
DOI: | 10.1152/ajpregu.00632.2002 |