Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

Kotz, Catherine M.; Grace, Martha K.; Briggs, John D.; Levine, Allen S.; Billington, Charles J.

doi:10.1172/jci118017

Cited by 86 publications

(44 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with these findings suggesting that the MOR pathway promotes fat deposition in lieu of fat oxidation, body weight changes in MOR Ϫ/Ϫ mice during food deprivation mirrored those seen with an adipogenic diet, including an increased weight loss associated with reduced FFA levels. Other studies using nonselective opioid receptor antagonists suggest that opioids may impair BAT and UCP-1 activity in a way that favors fat deposition (37,38). However, we found no evidence that the MOR pathway is involved in the regulation of UCP-1 expression during high-fat feeding.…”

Section: Discussioncontrasting

confidence: 93%

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

et al. 2005

View full text Add to dashboard Cite

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 ...

show abstract

Section: Discussioncontrasting

confidence: 93%

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

et al. 2005

View full text Add to dashboard Cite

show abstract

“…In particular, GLP-1 binding sites were found in the inferior olive and nucleus of the solitary tract (9); both areas have been described as involved in the control of thermogenesis (40,41). Although at the central level SIRT1/p53 and AMPK pathways are interacting to mediate the orexigenic actions of ghrelin (33), neither SIRT1 nor p53 modified liraglutide-induced hypophagia or weight loss, indicating that the brain SIRT1/p53 system does not interact with AMPK to mediate the actions of liraglutide on thermogenesis and browning.…”

Section: Discussionmentioning

confidence: 99%

GLP-1 Agonism Stimulates Brown Adipose Tissue Thermogenesis and Browning Through Hypothalamic AMPK

et al. 2014

View full text Add to dashboard Cite

GLP-1 receptor (GLP-1R) is widely located throughout the brain, but the precise molecular mechanisms mediating the actions of GLP-1 and its long-acting analogs on adipose tissue as well as the brain areas responsible for these interactions remain largely unknown. We found that central injection of a clinically used GLP-1R agonist, liraglutide, in mice stimulates brown adipose tissue (BAT) thermogenesis and adipocyte browning independent of nutrient intake. The mechanism controlling these actions is located in the hypothalamic ventromedial nucleus (VMH), and the activation of AMPK in this area is sufficient to blunt both central liraglutide-induced thermogenesis and adipocyte browning. The decreased body weight caused by the central injection of liraglutide in other hypothalamic sites was sufficiently explained by the suppression of food intake. In a longitudinal study involving obese type 2 diabetic patients treated for 1 year with GLP-1R agonists, both exenatide and liraglutide increased energy expenditure. Although the results do not exclude the possibility that extrahypothalamic areas are also modulating the effects of GLP-1R agonists, the data indicate that long-acting GLP-1R agonists influence body weight by regulating either food intake or energy expenditure through various hypothalamic sites and that these mechanisms might be clinically relevant.

show abstract

“…O nível circulante de leptina correlaciona-se com a quantidade de gordura corporal em animais e humanos (118)(119)(120). Em mulheres obesas e de peso normal de nossa população, obtivemos correlação entre leptinemia e adiposidade avaliada pelo índice de massa corpórea e pela porcentagem de gordura corporal (136). Obtivemos correlação significante entre adiposidade central medida pela relação abdome-quadril em pacientes brancas, porém não obtivemos em pacientes negras (136).…”

Section: H Leptinaunclassified

“…Antagonistas do NPY representam uma terapêutica promissora no tratamento da obesidade. O NPY é antagonizado por injeções parenterais de naloxona, sugerindo que pode haver uma ativação do sistema de receptores opióides pelo NPY, provavelmente no PVN (136).…”

Section: Agentes De Ação Centralunclassified

“…Estes efeitos podem ser bloqueados por antagonistas a receptores opióides κ. A estimulação de receptores opióides κ aumenta a ingestão de gordura e o uso de naloxone, um antagonista de receptores opióides, diminui a ingestão de gordura e interfere com o efeito orexígeno do NPY (137). Naltrexone, um antagonista opióide de longa ação, foi utilizado em ensaios clínicos, com resultados frustrantes em baixa dose.…”

Section: B Peptídeos Opióides Endógenosunclassified

See 1 more Smart Citation

Aspectos fisiológicos do balanço energético

Mancini

Halpern

2002

Arq Bras Endocrinol Metab

View full text Add to dashboard Cite

RESUMOconhecidos. Nesta revisão, abordamos os nutrientes, monoaminas e peptídeos que podem levar a redução da ingestão e, em alguns casos, aumentar a ingestão de alimentos. Vários desses mecanismos podem levar ao desenvolvimento de novas abordagens no tratamento da obesidade ou na elucidação do mecanismo de ação de agentes farmacológicos. NUTRIENTES Agentes de Ação Periférica a. Análogos e metabólitos da hexoseA teoria glicostática (1) propõe que taxas de utilização de glicose podem ser sinais para iniciar ou ultimar a ingestão alimentar.Glicose. Uma diminuição no nível de glicose pode preceder e iniciar a alimentação em animais e humanos (2,3). Infusões periféricas de glicose diminuem a ingestão alimentar em animais experimentais, sendo o nervo vago a conexão entre os glicorreceptores periféricos e o cérebro. Quando glicose é infundida na circulação portal, a descarga de aferentes vagais é reduzida à medida que a concentração de glicose aumenta (4). A infusão de glicose ou arginina diminui a taxa de transmissão aferente e aumenta a transmissão simpática eferente ao tecido adiposo marrom (5).

show abstract

Effects of opioid antagonists naloxone and naltrexone on neuropeptide Y-induced feeding and brown fat thermogenesis in the rat. Neural site of action.

Cited by 86 publications

References 48 publications

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

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

GLP-1 Agonism Stimulates Brown Adipose Tissue Thermogenesis and Browning Through Hypothalamic AMPK

Aspectos fisiológicos do balanço energético

Contact Info

Product

Resources

About