Leptin interacts with glucagon‐like peptide‐1 neurons to reduce food intake and body weight in rodents

Goldstone, Anthony P.; Mercer, Julian G.; Gunn, I.; Moar, Kim-Marie; Edwards, C. M. B.; Rossi, Michela; Howard, Jane K.; Rasheed, Shahnawaz; Turton, M. D.; Small, Caroline J.; Heath, Martha E.; O’Shea, Donal; Steere, Joanna; Meeran, Karim; Ghatei, Mohammed A.; Hoggard, Nigel; Bloom, Stephen R.

doi:10.1016/s0014-5793(97)01103-4

Cited by 129 publications

(73 citation statements)

References 26 publications

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“…In animals con¯icting results on leptin interactions with GLP-1 have been obtained. 42,43 In humans, however, there is no evidence of interactions between GLP-1 and leptin, cholecystokinin or somatostatin. 10,44 ± 46 On the other hand, the inhibition of gastric secretion by GLP-1 has been shown to depend on an intact n. vagus.…”

Section: Glp-1 Appetite and Metabolism In Obesity A Flint Et Almentioning

confidence: 99%

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

Flint¹,

Raben²,

Ersbøll³

et al. 2001

Int J Obes

319

228

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OBJECTIVE: Peripheral infusions of glucagon-like peptide-1 (GLP-1) in humans have been shown to inhibit gastrointestinal motility and decrease hunger and energy intake. However, these investigations used supraphysiological doses. The objective of this study was to investigate the effects of a GLP-1 infusion in a physiological dose on appetite sensations, energy intake, gastric emptying, energy and substrate metabolism. METHODS: Eighteen obese men participated in the placebo-controlled, randomized, single-blinded, cross-over study with infusion of GLP-1 or saline. Resting metabolic rate (RMR) and substrate oxidations were measured by ventilated hood before and after an energy-®xed breakfast. Gastric emptying was measured using paracetamol as a marker. Visual analogue scales were used to assess appetite sensations, thirst and comfort throughout the experiment and palatability of the test meals. Blood was sampled for analysis of hormones (GLP-1, GLP-2, glucose-dependent insulinotropic polypeptide (GIP), insulin, glucagon), and substrates (glucose, lactate, non-esteri®ed fatty acids (NEFA), triacylglycerol (TAG)). Ad libitum energy intake at lunch was registered. RESULTS: Following the breakfast, GLP-1 infusion suppressed ratings of hunger and prospective food consumption (P`0.05), whereas all other subjective ratings and ad libitum energy intake were unaffected. RMR, carbohydrate oxidation and gastric emptying rate were lower during the GLP-1 infusion compared with the saline infusion (P`0.001, P`0.05, P`0.0001, respectively). All plasma hormone and substrate pro®les, except NEFA, were signi®cantly reduced by GLP-1 (P`0.0001). CONCLUSION: It is concluded that GLP-1 in physiological concentrations powerfully reduces the rate of entry of nutrients into the circulation by a reduction of gastric emptying rate in obese subjects. The effect of GLP-1 on appetite and food intake may be bene®cial in weight reduction.

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Section: Glp-1 Appetite and Metabolism In Obesity A Flint Et Almentioning

confidence: 99%

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

Flint¹,

Raben²,

Ersbøll³

et al. 2001

Int J Obes

319

228

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“…In addition, they found that leptin inhibition of food intake can be prevented by blockade of GLP-1 receptor activity. 46 However, this effect does not necessarily suggest GLP-1 receptor involvement in all down-stream actions of leptin. GLP-1 receptor deficient mice have normal body weights, 10 while it is well known that leptin receptor-deficient rodents (db/db mice, fa/fa Zucker rats) become morbidly obese.…”

Section: Glp-1 Reduces Short-term Food Intakementioning

confidence: 97%

Glucagon-like peptide-1 (7–36) amide: a central regulator of satiety and interoceptive stress

Dijk

Thiele

1999

Neuropeptides

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INTRODUCTIONIngestion of food is a necessary and pleasant occupation that allows humans and other species to maintain caloric homeostasis and a certain level of body weight. Ironically, in doing so, one's 'milieu interieur' is put at risk because meal-induced fuel excursions can have deleterious effects on metabolic (e.g. glycosylation causing loss of enzymatic efficacy) and cardiovascular (e.g. triglyceride accumulation, increased blood pressure, etc.) processes. 1,2 To reduce these perturbations to a minimum, evolution has provided many species (including humans and rodents) with a fine-tuned system enabling ingested nutrients to be anticipated, efficiently digested, and stored. 3 One of these mechanisms includes passage of nutrients through the digestive tract, triggering the release of a number of peptides from endocrine cells located in the wall of various parts of the gastrointestinal tract. These peptides serve important functions in facilitating the process of nutrient digestion/storage. Among these, the truncated (i.e. 7-36) amidated form of glucagon-like peptide-1 (GLP-1) has attracted considerable attention over the last several years. Firstly, because of its remarkable peripheral insulinotropic effects that could be useful for clinical purposes. Secondly, because more recent data suggest an important role of this peptide in the central nervous system (CNS) control of ingestive behavior. Although the present paper mainly focusses on the latter issue, a short review of peripheral GLP mechanisms is necessary for a better understanding of the processes that relate GLP-1 to food intake. GLP-1 FROM THE GASTROINTESTINAL TRACTGLP-1 is processed from proglucagon in mucosal L cells of the distal portion of the ileum and in the A cells of the pancreas. Ingested food, particularly when rich in carbohydrates, causes the level of circulating GLP-1 (mainly of ileal origin) to increase, and in turn, GLP-1 potently stimulates the secretion of insulin from pancreatic B cells via receptor-mediated processes (for reviews, see refs 4 and 5). In contrast, it reduces the secretion of glucagon, at least under ad libitum feeding conditions. 6 While GLP-1 may have some direct stimulatory effects on glucose clearance in peripheral tissue 7,8 (presumably via activation of specific GLP-1 receptors in liver, muscle, kidney Summary Glucagon-like peptide-1 (7-36) amide (GLP-1) is processed from proglucagon in the distal ileum as well as in the CNS. In the periphery, GLP-1 acts as an incretin factor and profoundly inhibits upper gastrointestinal motility ('ileal brake'), the latter presumably involving the CNS. Within the CNS, GLP-1 has a satiating effect, since administration of GLP-1 into the third cerebral ventricle reduces short-term food intake (and meal size), while administration of GLP-1 antagonists have the opposite effect. In addition, activation of GLP-1 receptors in certain brain regions elicits strong taste aversions. Similarities between toxin-and GLP-1-induced neuronal activity in the CNS (brain stem) suggest a role f...

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“…A administração intra-cerebroventricular de CART e de seu anticorpo específico teve, respectivamente, efeito inibitório e efeito estimulatório da ingestão, sendo sugerido que o peptídeo CART endógeno manteria um tônus inibitório sobre a ingestão alimentar (188). Além disso, a injeção central de CART antes de NPY bloqueia a hiperfagia induzida pelo NPY em ratos normais (188).…”

Section: Transcrito Regulado Por Cocaína E Anfetamina (Cart)unclassified

“…Além disso, a injeção central de CART antes de NPY bloqueia a hiperfagia induzida pelo NPY em ratos normais (188). Ratos submetidos à privação de alimento apresentam redução da expressão de CART no ARC e em modelos animais de obesidade com ausência de sinalização da leptina (camundongo ob/ob, rato Zucker fa/fa) essa expressão é quase nula, sendo estimulada pela administração periférica de leptina (188). Postulou-se que a supressão da ingestão alimentar mediada pela leptina envolveria a diminuição do NPY e a indução do CART (188).…”

Section: Transcrito Regulado Por Cocaína E Anfetamina (Cart)unclassified

“…Neurônios do tronco cerebral co-expressam o RNAm do receptor de leptina e do GLP-1, e a administração de exendina bloqueia a inibição induzida por leptina da ingestão alimentar. Isso pode indicar que a via do GLP-1 pode ser um dos mediadores dos efeitos anoréticos da leptina (188), muito embora camundongos com deleção do gene do receptor de GLP-1 não exibam anormalidades do comportamento alimentar (189). Estudos em humanos demonstraram que a administração periférica de GLP-1 exerce influências sobre sensações subjetivas de apetite e reduz a ingestão de alimento em voluntários (190).…”

Section: J Crh E Urocortinaunclassified

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Aspectos fisiológicos do balanço energético

Mancini

Halpern

2002

Arq Bras Endocrinol Metab

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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).

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Leptin interacts with glucagon‐like peptide‐1 neurons to reduce food intake and body weight in rodents

Cited by 129 publications

References 26 publications

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity

Glucagon-like peptide-1 (7–36) amide: a central regulator of satiety and interoceptive stress

Aspectos fisiológicos do balanço energético

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