Mode of action of OB protein (leptin) on feeding
American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyPublished 1 July 1998
Mark C Flynn, Thomas R. Scott, Thomas C. Pritchard, Carlos R. Plata‐Saláman
Citations115
SJR quartileQ2
SJR score0.94
SNIP0.90
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
Results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size, which was observed during the daytime and total daily periods.
Abstract
OB protein (leptin) decreases food intake in a variety of species. Here we investigated the effects of the intracerebroventricular administration of recombinant murine OB protein on food consumption and meal parameters in Wistar rats maintained ad libitum. The intracerebroventricular administration of OB protein (0.56-3.5 microg/rat) decreased feeding in a dose-dependent manner. Computer analysis of meal parameters demonstrated that OB protein (3.5 microg/rat, n = 10) decreased nighttime meal size by 42%, whereas meal frequency and meal duration were unaffected. Derived analyses for the nighttime also showed that OB protein decreased the feeding rate (meal size/meal duration) by 30%, whereas the satiety ratio (intermeal intervals/meal size) increased by 100%. A similar profile was observed during the daytime and total daily periods. The intracerebroventricular administration of heat-inactivated OB protein (3.5 microg/rat, n = 10) had no effect on any meal parameter. The results show that OB protein administered intracerebroventricularly inhibits feeding through a specific reduction of meal size.
Keywords
MedicineNeuroscienceNursing
ScienceWeight-Reducing Effects of the Plasma Protein Encoded by the <i>obese</i> Gene
4,455 Citations1995Jeffrey L. Halaas, K.S. Gajiwala +7 more
Injection of wild-type mice twice daily with the mouse protein resulted in a sustained 12 percent weight loss, decreased food intake, and a reduction of body fat from 12.2 to 0.7 percent, suggesting that the OB protein serves an endocrine function to regulate body fat stores.
ScienceEffects of the <i>obese</i> Gene Product on Body Weight Regulation in <i>ob</i> / <i>ob</i> Mice
4,022 Citations1995Mary Ann Pelleymounter, Mary Jane Cullen +5 more
The data suggest that the OB protein regulates body weight and fat deposition through effects on metabolism and appetite.
ScienceRecombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks
3,269 Citations1995L. Arthur Campfield, Françoise J. Smith +3 more
The behavioral effects after brain administration suggest that OB protein can act directly on neuronal networks that control feeding and energy balance in ob/ob and diet-induced obese mice.
NatureRole of melanocortinergic neurons in feeding and the agouti obesity syndrome
1,908 Citations1997Wei Fan, Bruce A. Boston +3 more
The authors' data show that melanocortinergic neurons exert a tonic inhibition of feeding behaviour, and chronic disruption of this inhibitory signal is a likely explanation of the agouti obesity syndrome.
NatureThe role of neuropeptide Y in the antiobesity action of the obese gene product
1,513 Citations1995Thomas W. Stephens, Margret B. Basinski +15 more
Journal of Clinical InvestigationIdentification of targets of leptin action in rat hypothalamus.
1,501 Citations1996Michael W. Schwartz, Randy J. Seeley +3 more
The findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.
DiabetesSpecificity of Leptin Action on Elevated Blood Glucose Levels and Hypothalamic Neuropeptide Y Gene Expression in <i>ob/ob</i> Mice
871 Citations1996Michael W. Schwartz, Denis G. Baskin +9 more
In ob/ob mice, systemic administration of leptin inhibits NPY gene overexpression through a specific action in the arcuate nucleus and exerts a hypoglycemic action that is partly independent of its weight-reducing effects.
EndocrinologyProopiomelanocortin Neurons Are Direct Targets for Leptin in the Hypothalamus
741 Citations1997Clement C. Cheung, Donald K. Clifton +1 more
The expression of the leptin receptor in several hypothalamic nuclei suggests that multiple neuronal subtypes are targets for leptin's action, and it is inferred that POMC neurons and the products of the PomC gene may be part of the signaling pathway mediating leptin'saction on feeding and perhaps other physiological functions.
PeptidesBiological actions of cholecystokinin
717 Citations1994Jacqueline N. Crawley, Rebecca L. Corwin
New findings are presented on potent, nonpeptide CCK antagonists, selective for the two CCK receptor subtypes, which demonstrate that endogenous CCK has biologically important effects on physiology and behavior.
Hormone and Metabolic ResearchThe OB Protein (Leptin) Pathway - A Link Between Adipose Tissue Mass and Central Neural Networks
505 Citations1996L. Arthur Campfield, Franklin R. Smith +1 more
Journal of NeuroendocrinologyCoexpression of Leptin Receptor and Preproneuropeptide Y mRNA in Arcuate Nucleus of Mouse Hypothalamus
464 Citations1996Julian G. Mercer, Nigel Hoggard +5 more
Dual in situ hybridization studies for leptin receptor and NPY gene expression in the mouse arcuate nucleus are reported, providing the first direct evidence that leptin acts on cells that express NPY mRNA.
Proceedings of the National Academy of SciencesSynergistic interaction between leptin and cholecystokinin to reduce short-term food intake in lean mice
439 Citations1997M D Barrachina, Vicente Martı́nez +3 more
The results indicate the existence of a functional synergistic interaction between leptin and CCK leading to early suppression of food intake which involves CCK-A receptors and capsaicin-sensitive afferent fibers.
EndocrinologyLeptin Activates Neurons in Ventrobasal Hypothalamus and Brainstem
423 Citations1997Joel K. Elmquist, Rexford S. Ahima +3 more
It is reported that systemic administration of leptin activates nuclear groups in the ventrobasal hypothalamus, including the ventromedial, dorsomedial, and ventral premammillary hypothalamic nuclei.
American Journal of Clinical NutritionModel for the regulation of energy balance and adiposity by the central nervous system
327 Citations1999Michael W. Schwartz, Denis G. Baskin +2 more
This review integrates new information into a revised model of energy homeostasis that proposes that long-term adiposity-related signals such as insulin and leptin influence the neuronal activity of central effector pathways that serve as controllers of energy balance.
EndocrinologyEffects of Leptin on Insulin Sensitivity in Normal Rats*
258 Citations1997William I. Sivitz, Susan A. Walsh +3 more
Leptin increased insulin sensitivity in normal rats both under fasting conditions and in the presence of hyperinsulinemia at clamped glucose, and these effects did not appear dependent on altered body weight.
NutritionAnorexia during acute and chronic disease
248 Citations1996Carlos R. Plata‐Saláman
Understanding the specific mechanisms responsible for anorexia during disease as well as their interactions is essential to develop interventions for the control of anorexigenic substances and to devise less toxic immunotherapeutic regimens using cytokines.
Neuroscience & Biobehavioral ReviewsThe direct and indirect controls of meal size
228 Citations1996Gerard P. Smith
A new classification of the controls of meal size based on an unambiguous physical criterion and a method of measuring the potency of direct and indirect controls is described, which explicates the functional relationship between indirect and direct controls.
DiabetesInteractions Between Leptin and Hypothalamic Neuropeptide Y Neurons in the Control of Food Intake and Energy Homeostasis in the Rat
215 Citations1997Qiong Wang, Chen Bing +16 more
Leptin acts centrally to decrease NPY synthesis and NPY levels in the ARC-PVN projection; reduced NPY release in the PVN may mediate leptin's hypophagic and thermogenic actions; Conversely, NPY-induced obesity results in raised circulating leptin concentrations.
DiabetesThe Weight-Reducing Effect of an Intracerebroventricular Bolus Injection of Leptin in Genetically Obese <i>fa/fa</i> Rats: Reduced Sensitivity Compared With Lean Animals
206 Citations1996Isabelle Cusin, Françoise Rohner‐Jeanrenaud +2 more
ICV leptin injections were able to decrease neuropeptide Y (NPY) levels in the arcuate and paraventricular hypothalamic nuclei in both lean and genetically obese fa/fa rats, although a higher leptin dose was again needed in the obese group, providing further evidence for the implication of NPY and leptin in a regulatory loop controlling body homeostasis.
Physiology & BehaviorCentral insulin enhances sensitivity to cholecystokinin
172 Citations1995Chris Riedy, Mark Chavez +2 more
Results are consistent with the hypothesis that central insulin acts by altering sensitivity to satiety agents and enhanced the anorexic effect of Cholecystokinin.
PeptidesAnalysis of neuropeptide Y-induced feeding: Dissociation of Y1 and Y2 receptor effects on natural meal patterns
149 Citations1991Sarah F. Leibowitz, Jesline T. Alexander
It is proposed that hypothalamic Y1 receptors mediate the stimulatory effect of NPY on carbohydrate intake and meal size, while Y2 receptors have the opposite effect of suppressing carbohydrate intake, possibly by altering presynaptic release of monoamines known to influence nutrient ingestion.
DiabetesThe Effect of Leptin Is Enhanced by Microinjection Into the Ventromedial Hypothalamus
136 Citations1997Ralph Jacob, James Dziura +6 more
It is concluded that small doses of leptin that do not effect eating behavior when delivered to the ventricle or the dorsal raphe (another brain region believed to regulate feeding), suppress food intake when injected into the VMH.
FEBS LettersLeptin interacts with glucagon‐like peptide‐1 neurons to reduce food intake and body weight in rodents
133 Citations1997Anthony P. Goldstone, Julian G. Mercer +15 more
ICV injection of the specific GLP‐1 receptor antagonist, exendin, at the onset of dark phase, did not affect feeding in saline pre‐treated controls, but blocked the reduction in food intake and body weight of leptin pre‐ treated rats, suggesting that GLp‐1 neurons are a potential target for leptin in its control of feeding.
Brain Research BulletinDiurnal variations in the feeding responses to norepinephrine, neuropeptide Y and galanin in the PVN
114 Citations1990Donna L. Tempel, Sarah F. Leibowitz
Feeding responses elicited by injection of norepinephrine, neuropeptide Y and galanin into the paraventricular nucleus of male Sprague-Dawley rats were studied at two different times of the dark cycle, reflecting differential functions of these hypothalamic neurotransmitters in controlling nutrient ingestion at different periods of the circadian cycle.
PeptidesNeuropeptide Y blocks and reverses interleukin-1β-induced anorexia in rats
103 Citations1996Gayatri Sonti, Sergey E. Ilyin +1 more
Results show that ICV-administered NPY blocks and reverses the anorexia induced by estimated pathophysiological and pharmacological concentrations of IL-1 beta in rats, suggesting the importance in studying cytokine-peptide interactions in the regulation of feeding behavior.
American Journal of Clinical NutritionNew model for the regulation of energy balance and adiposity by the central nervous system
100 Citations1995KJ Kaiyala, S C Woods +1 more
Through this mechanism, the central nervous system response to short-term signals is adjusted in proportion to changes in body adiposity, resulting in compensatory changes in food intake and energy expenditure that collectively favor the long-term stability of fat stores.
Physiology & BehaviorMeal patterns in response to the intracerebroventricular administration of interleukin-1β in rats
99 Citations1994Carlos R. Plata‐Saláman
Evidence suggests specificity of IL-1 beta inducing behavioral changes by direct action in the central nervous system is required for this substance to be effective in rats maintained ad lib.
Journal of Biological ChemistryCorticotropin-releasing Factor and Adrenocorticotrophic Hormone as Potential Central Mediators of OB Effects
86 Citations1997Jacob Raber, Shizhong Chen +2 more
It is shown in mice that both the long and short form of the OB receptor are expressed not only in the hypothalamus but also in the amygdala and pituitary, which may be pertinent to human obesity, which combines increased plasma glucocorticoid levels with elevated levels of OB.
American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyInterferons and central regulation of feeding
61 Citations1992Carlos R. Plata‐Saláman
The results suggest that IFN acts directly in the central nervous system to decrease short-term feeding, consistent with the species specificity to the effects of IFNs.
Physiology & BehaviorInsulin is a prandial satiety hormone
54 Citations1994Dennis A. Vanderweele
When insulin is increased during spontaneously taken meals, those meals are reduced in size and drugs which block insulin release, increase the size of meals; it is asserted insulin is a prandial satiety hormone which likely reduced feeding by increasing glucose uptake into peripheral tissue.
American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyInterleukin-8 modulates feeding by direct action in the central nervous system
41 Citations1993Carlos R. Plata‐Saláman, Jeffrey P. Borkoski
The results suggest that IL-8 acts directly in the central nervous system to decrease feeding, and may contribute to the food intake suppression frequently accompanying pathological processes.
NutritionAnorexia during acute and chronic disease: Relevance of neurotransmitter-peptide-cytokine interactions
31 Citations1997Carlos R. Plata‐Saláman
American Journal of Physiology-Regulatory, Integrative and Comparative PhysiologyModulation of feeding by beta 2-microglobulin, a marker of immune activation
12 Citations1995Carlos R. Plata‐Saláman, Gayatri Sonti +1 more
The results suggest that beta 2-microglobulin may act centrally to decrease feeding, and this effect may participate in the anorexia frequently accompanying pathological processes.