Naltrexone reduces weight gain, alters “β-endorphin”, and reduces insulin output from pancreatic islets of genetically obese mice

Recant, Lillian; Voyles, Nancy R.; Luciano, Mark; Pert, Candace B.

doi:10.1016/0196-9781(80)90008-x

Cited by 105 publications

(39 citation statements)

References 10 publications

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“…These findings contrast with those of naloxone and naltrexone treatment, which require significantly higher doses or parenteral administration (20,22,33). The actions of LY255582 were mediated through occupancy of opioid receptors as demonstrated by ex vivo receptor binding.…”

Section: Discussioncontrasting

confidence: 52%

“…12,34), the effects of chronic naltrexone or naloxone administration on body weight are equivocal. Several studies have reported sustained reductions in food intake and body weight in rodents after chronic administration of naltrexone or naloxone (1,21,22,33). However, others failed to observe long-term alterations in food intake or body weight with naloxone or naltrexone treatment (28,30,32,39).…”

Section: Discussionmentioning

confidence: 99%

“…The reason for the disparity between the acute effects of opioid receptor antagonists and chronic effects is unknown. One possible explanation may be derived from rodent studies where naloxone and naltrexone appear to consistently reduce body weight in normal weight, genetically obese, or rapidly growing animals, but have limited efficacy in animals with dietary-induced obesity (20,22,33). Therefore, the etiology of the obese phenotype may play a particularly important role in determining if intervention with an opioid receptor antagonist will be efficacious.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, endogenous opioid peptides (␤-endorphin, the enkephalins, and dynorphin) are elevated in obesity and by fasting (6,9,14,21,44). Numerous studies using antagonists to opioid receptors report reduced food intake and body weight in rodents (1,17,21,22,33,38,39). Interestingly, the inhibitory effects of opioid receptor antagonists on food intake and body weight appear most pronounced in obese animals or when animals are fed a highly palatable diet (12,19).…”

mentioning

confidence: 99%

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Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

Statnick

Tinsley

Eastwood

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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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-, κ-, and δ-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.

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

Statnick

Tinsley

Eastwood

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Thus, ob/ob mice exhibit raised levels of B-endorphin, metS-enkephalin and leuS-enkephalin in the pituitary, hypothalamus and pancreas [36][37][38][39][40][41]. The ob/ ob mice also show heightened feeding and drinking responses to opiate agonists and antagonists, particularly those acting predominantly at K-opiate receptors [36,40,42]. The present study provides evidence of disturbances in the glucoregulatory effects of opiates in ob/ ob mice.…”

Section: Discussionmentioning

confidence: 71%

Increased responsiveness to glucoregulatory effect of opiates in obese-diabetic ob/ob mice

Bailey

Flatt

1987

Diabetologia

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Plasma glucose and insulin responses to opiate receptor stimulation and antagonism were determined in 12-14 week old lean and obese-diabetic Aston ob/ob mice. The opiate receptor antagonist naloxone (1 mg/kg intraperitoneally) rapidly and transiently raised glucose and suppressed insulin concentrations in lean mice, and produced qualitatively similar but more protracted response in ob/ob mice. Selective stimulation of mu- and delta-opiate receptors using the enkephalin analogues Tyr-D-Ala-Gly-MePhe-NH(CH2)2OH (1 mg/kg, intraperitoneally) and Tyr-D-Ala-Gly-Phe-D-Leu (10 mg/kg intraperitoneally) respectively, rapidly and transiently increased glucose and insulin concentrations in lean and ob/ob mice. The ob/ob mice exhibited greater glucose and insulin responses to these analogues. The results provide evidence that endogenous opiates participate in the regulation of glucose and insulin homeostasis, and suggest that increased responsiveness to mu- and delta-opiate receptor stimulation may contribute to the hyperglycaemia and hyperinsulinaemia of obese-diabetic mice.

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Central Nervous System Control of Nutrient Homeostasis

Woods

Taborsky

Porte

1986

Comprehensive Physiology

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Naltrexone reduces weight gain, alters “β-endorphin”, and reduces insulin output from pancreatic islets of genetically obese mice

Cited by 105 publications

References 10 publications

Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

Antagonism of opioid receptors reduces body fat in obese rats by decreasing food intake and stimulating lipid utilization

Increased responsiveness to glucoregulatory effect of opiates in obese-diabetic ob/ob mice

Central Nervous System Control of Nutrient Homeostasis

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