Endogenous Opiates and Energy Balance

Mandenoff, A; Fumeron, Frédéric; Apfelbaum, M; Margules, David L.

doi:10.1126/science.7063865

Cited by 104 publications

(38 citation statements)

References 14 publications

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“…These alterations were revealed only by an adipogenic dietary challenge because deletion of the MOR had no effect on body weight, fat mass, or glucose metabolism in adult mice fed a low-fat diet. These results agree with the modest effects of long-acting opioid receptor antagonists on the body weight of rats fed a regular diet and the ability of these agents to prevent weight gain in rats fed an adipogenic diet (6,24). However, in contrast to the findings observed with pharmacological agents, the decreased vulnerability to diet-induced obesity observed in mice selectively deficient for the MOR is attributable to changes in energy metabolism and not in caloric intake.…”

Section: Discussioncontrasting

confidence: 35%

“…It has been suggested that opioids favor the conservation of energy because the weight reduction induced by opioid antagonists in rats fed an adipogenic diet exceeded the degree to which caloric intake was reduced (6,24). However, controversial results on energy expenditure have been obtained with pharmacological tools (6,7). Two studies have reported that nonselective opioid antagonists induce a decrease in RQ, thereby indicating an opioid modulation of lipid oxidation, in rats fed regular and high-fat diets (7,8).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast to the extensive work on the involvement of opioids in feeding behavior, little information is available about a role of the opioid system in energy metabolism. It has been suggested that opioids favor the conservation of energy because the weight reduction induced by opioid antagonists in rats fed an adipogenic diet exceeded the degree to which caloric intake was reduced (6,24). However, controversial results on energy expenditure have been obtained with pharmacological tools (6,7).…”

Section: Discussionmentioning

confidence: 99%

“…However, in those trials, these agents were nonselective and were given to already obese people. It should be emphasized that more consistent weight-reducing effects in rats were obtained with administration of opioid-receptor antagonists before or during the dynamic phase of obesity development than in animals with preexisting dietary obesity (6,8,24). Also, individual differences in the etiology of obesity (28) may play a role in the efficacy of an opioid receptor antagonist.…”

Section: Discussionmentioning

confidence: 99%

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Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

et al. 2005

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Using pharmacological tools, a role for opioid receptors in the regulation of food intake has been documented. However, the involvement of specific receptor subtypes remains questionable, and little information is available regarding a role for opioid receptors in energy metabolism. Using adult male mice lacking the -opioid receptor (MOR) gene (MOR ؊/؊ ), we show that the MOR is not essential for the maintenance of normal levels of ad libitum food intake but does modulate the efficiency of energy storage during high-fat diets through the regulation of energy partitioning. When fed a regular diet, MOR ؊/؊ mice displayed only subtle alterations in energy homeostasis, suggesting a relative overuse of fat as a fuel source in the fed state. When fed a high-fat diet, MOR ؊/؊ mice were resistant to obesity and impaired glucose tolerance, despite having similar energy intake to wild-type mice. This resistance to obesity was associated with a strong induction of the expression of key mitochondrial enzymes involved in fatty acid oxidation within skeletal muscle. This metabolic role of the MOR, which is consistent with the properties of a "thrifty gene," suggests that the MOR pathway is a potential target for pharmacological intervention in the treatment of obesity associated with the intake of fatty diets. Diabetes 54: 3510 -3516, 2005 T he endogenous opioid system encompasses cloned receptor populations (, ␦, and ) and ligands (␤-endorphin, the enkephalins, and the dynorphins). Extensive work indicates that the opioid system plays a role in the regulation of appetite. Opioid receptors and peptides are expressed in sites of the central nervous system that play a role in regulating feeding behavior, and pharmacological experiments using opioid receptor ligands show that agonists promote eating and antagonists decrease food intake, at least in the short term (1-3). Numerous pharmacological studies indicate that opioids also play a role in modulating the rewarding effects of food (3-5). In contrast, little information suggests that opioids have a role in energy metabolism (6 -8).The need to establish the specific role of the opioid receptors in energy homeostasis has led to studies using putative specific opioid receptor ligands or, more recently, antisense probes directed against specific exons of opioid receptor genes (3,9). Pharmacological studies suggest that the and pathways are part of an interconnected brain network and participate in the orexigenic effect of several peptides that regulate food intake (10 -13). However, the interpretation of these data is complicated by our poor knowledge of the in vivo selectivity of ligand-receptor interactions that have been established in vitro (9,14).Recent studies conducted in mutant mice null for the opioid receptors have complemented pharmacological approaches and clarified the role of each receptor in nociception, anxiety, and drug abuse (14). To further define the role of the -opioid receptor (MOR) pathway in energy homeostasis, we characterized mice lacking the MOR gene ...

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Section: Discussioncontrasting

confidence: 35%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

et al. 2005

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“…How ingestion of palatable food is regulated is of great interest to those studying ingestive behavior as well as those studying basic mechanisms of motivation and reward. One of the first neurochemical systems implicated in the hedonics of feeding and obesity was the endogenous opioid system (Belluzzi and Stein, 1977;Mandenoff, et al, 1982;Margules, et al, 1978). In general, opioid antagonists are anorexigenic while opioid agonists are orexigenic [reviewed in (Bodnar, 2004;Glass, et al, 1999)].…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Differential involvement of endogenous opioids in sucrose consumption and food reinforcement

Hayward

Schaich-Borg

Pintar

et al. 2006

Pharmacology Biochemistry and Behavior

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Endogenous opioids within the central nervous system are postulated to mediate hedonic aspects of feeding behavior. To identify the relevant endogenous opioid receptor ligands, mice lacking one or two of the opioid peptide families β-endorphin, enkephalins or dynorphins were tested for sucrose preference in a two-bottle free-choice drinking paradigm under drug-naïve conditions and following treatment with an opioid antagonist (1 mg/kg naloxone i.p.) or saline. Basal sucrose consumption was unaltered in all of the knockout genotypes compared to their congenic wild-type C57BL/6 littermates during 0.5 and 6 h access to a bottle containing 2, 4, 8, or 16% sucrose and a second bottle containing water. Moreover, all mutant genotypes and wildtype mice exhibited a similar compensatory decrease in overnight food intake following the extra caloric load from 6 h sucrose access. Although these basal responses to sucrose were unaffected by the knockout genotypes, naloxone reduced sucrose consumption by 50% compared to saline treatment during the first 0.5 h in wild-type and β-endorphin knockout mice, but had no effect in enkephalin knockouts, β-endorphin and enkephalin double knockouts, or dynorphin knockouts. These data suggest that naloxone reduces sucrose consumption in wild-type mice by blocking endogenous enkephalin and/or dynorphin signaling, but not β-endorphin. Dynorphin knockouts in the current study had bar-pressing responses for a palatable food reinforcer in an operant procedure under free-feeding conditions similar to wildtype mice while we found in a previous study that β-endorphin and enkephalin knockout mice had reduced motivation to respond (Hayward, et al., 2002). We conclude from these studies directly comparing three strains of opioid peptide knockout mice that enkephalin and dynorphin can modulate sucrose preference but are not necessary to support sucrose consumption. However, dynorphin was not necessary to support wildtype levels of operant responding suggesting that only enkephalin and β-endorphin modulate conditioned food reinforcement. KeywordsOperant behavior; β-endorphin; enkephalin; dynorphin; knockout mice; ingestive behavior * Corresponding author phone: 609-235-1430 fax: 609-235-1498 e-mail: Michael.Hayward@Xenogen.com. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe plentiful access to calorically dense and highly palatable food choices is a likely contributor to the current obesity epidemic. How ingestion of palatable food is regulated is of great i...

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An auto-addiction opioid model of chronic anorexia nervosa

Marrazzi

Luby

1986

Int. J. Eat. Disord.

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The phenomenology of chronic anorexia nervosa is compared with that of addictive states. A model is proposed in which brain opioids mediate the elation, neuroendocrine changes, and down‐regulation of metabolism that occur in adaptation to dieting. The physiology of opioids is reviewed, and clinical and animal data are marshalled to support an auto‐addictive model. Opiate blockade together with therapeutic approaches used in the addictions may prove helpful in this stubborn disorder.

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Endogenous Opiates and Energy Balance

Cited by 104 publications

References 14 publications

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

Differential involvement of endogenous opioids in sucrose consumption and food reinforcement

An auto-addiction opioid model of chronic anorexia nervosa

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