Paraventricular nucleus injections of naloxone methiodide inhibit NPYʼs effects on energy substrate utilization

Currie, Paul J.; Coscina, Donald V.; Moretti, John A.; Avellino, Maria D.

doi:10.1097/00001756-200003200-00016

Cited by 8 publications

(5 citation statements)

References 18 publications

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“…The primary site of metabolic opioid actions remains to be determined. A brain site of opioid action is suspected (24,39,40). As an alternative, a direct peripheral action might be considered, although the presence of the MOR in liver and skeletal muscle remains poorly documented (41)(42)(43)(44).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2005

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“…Therefore, ODT8-SST could increase gastric emptying via the recruitment of NPY-Y 1 signaling as observed for the stimulation of food intake. Naloxone may interfere with the NPY-Y 1 -mediated action as demonstrated for the central NPY-induced increase in respiratory quotient that is dampened by naloxone (81).…”

Section: Figmentioning

confidence: 99%

Central Injection of the Stable Somatostatin Analog ODT8-SST Induces a Somatostatin2 Receptor-Mediated Orexigenic Effect: Role of Neuropeptide Y and Opioid Signaling Pathways in Rats

et al. 2010

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Somatostatin and octreotide injected into the brain have been reported to modulate food intake. However, little is known regarding the underlying mechanisms. The stable oligosomatostatin analog, des-AA 1,2,4,5,12, ]-somatostatin (ODT8-SST), like somatostatin, binds to all five somatostatin receptors (sst 1-5 ). We characterized the effects of ODT8-SST injected intracerebroventricularly (icv) on food consumption and related mechanisms of action in freely fed rats. ODT8-SST (0.3 and 1 g per rat, icv) injected during the light or dark phase induced an early onset (within 1 h) and long-lasting (4 h) increase in food intake in nonfasted rats. By contrast, ip injection (0.3-3 mg/kg) or icv injection of selective sst 1 or sst 4 agonists (1 g per rat) had no effect. The 2 h food intake response during the light phase was blocked by icv injection of a sst 2 antagonist, the neuropeptide Y (NPY) Y 1 receptor antagonist, BIBP-3226, and ip injection of the -opioid receptor antagonist, naloxone, and not associated with changes in plasma ghrelin levels. ODT8-SST (1 g per rat, icv) stimulated gastric emptying of a solid meal which was also blocked by naloxone. The increased food intake was accompanied by a sustained increase in respiratory quotient, energy expenditure, and drinking as well as -opioid receptor-independent grooming behavior and hyperthermia, while ambulatory movements were not altered after ODT8-SST (1 g per rat, icv). These data show that ODT8-SST acts primarily through brain sst 2 receptors to induce a long-lasting orexigenic effect that involves the activation of Y 1 and opiate-receptors, accompanied by enhanced gastric transit and energy expenditure suggesting a modulation of NPYergic and opioidergic orexigenic systems by brain sst 2 receptors. (Endocrinology 151: 4224 -4235, 2010)

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“…Such implications were shown in our previous study, in which nutritional manipulations augmented activity of this population of NPY-positive fibers, and simultaneously a decrease in hypothalamic somatostatin output was found Gładysz et al, 2001). The other NPY fibers located in the PVN nucleus, sensitive to variations of diets are involved in the stimulation of feeding behaviour (Yokosuka et al, 1999) and especially in the energy substrate utilization (Currie et al, 2000). In summary, it can be hypothesized that observed variations in the immunoreactivity of the NPY and GnRH indicate on the enhanced neurosecretory activity of the NPY neurons located in the ARC nucleus and on restrained release of GnRH from the nerve terminals in the ME.…”

Section: Discussionmentioning

confidence: 99%