Author
Harvey J. Grill
Other affiliations: Beth Israel Deaconess Medical Center, Rockefeller University
Bio: Harvey J. Grill is an academic researcher from University of Pennsylvania. The author has contributed to research in topics: Leptin & Forebrain. The author has an hindex of 63, co-authored 168 publications receiving 13834 citations. Previous affiliations of Harvey J. Grill include Beth Israel Deaconess Medical Center & Rockefeller University.
Topics: Leptin, Forebrain, Gastric emptying, Taste aversion, Taste
Papers published on a yearly basis
Papers
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TL;DR: These normative data for the intact rat can be directly compared to the taste reactivity of neurally ablated preparations which do not spontaneously feed or drink and can be utlized in determining the neural substrates necessary for the execution and regulation of ingestive behavior.
1,134 citations
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University of Tübingen1, Novo Nordisk2, Imperial College London3, Duke University4, Lunenfeld-Tanenbaum Research Institute5, Ulster University6, University of Cambridge7, University of Pennsylvania8, Harvard University9, University of Copenhagen10, ETH Zurich11, Ruhr University Bochum12, University of Cincinnati Academic Health Center13, Janssen Pharmaceutica14, University of Michigan15, University of Cincinnati16, Indiana University17, Technische Universität München18
TL;DR: The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.
Abstract: Background The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity. Scope of review In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases. Major conclusions Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders
679 citations
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TL;DR: Based on the similarities in the ingestion and rejection responses of decerebrate and intact rats, it appears that discriminative responses to taste result from integrative mechanisms complete within, or caudal to, the midbrain.
564 citations
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TL;DR: Food-deprived decerebrate rats, like intact ones, ingested a taste substance they had rejected when sated, but these same decerebrates neither rejected nor decreased ingestive reactions to a novel taste after that taste had been repeatedly paired with lithium chloride-induced illness.
Abstract: Taste substances applied to the oral cavity result in either ingestion or rejection, each with a characteristic muscular response pattern. These responses are the same in decerebrate and intact rats; the caudal brainstem appears to be the neural substrate of ingestion and rejection responses. The experiment determined whether decerebrates can alter these discriminative responses as a function of food deprivation or toxicosis. Food-deprived decerebrate rats, like intact ones, ingested a taste substance they had rejected when sated. However, these same decerebrates, in contrast to controls, neither rejected nor decreased ingestive reactions to a novel taste after that taste had been repeatedly paired with lithium chloride-induced illness. Although the forebrain may be important for integrating ingestion, some aspects of this control seem to be represented in caudal brain areas.
411 citations
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TL;DR: The results indicate that the CBS contains neurons that are potentially direct targets for the action of leptin in the control of energy homeostasis.
Abstract: Three experiments were performed to investigate the hypothesis that leptin action within the caudal brain stem (CBS) contributes to its intake inhibitory effects. The first experiment evaluated the anatomical distribution of leptin receptor mRNA in rat CBS using a sensitive fluorescence in situ hybridization method with a riboprobe specific for the long form of the leptin receptor (Ob-Rb). An Ob-Rb mRNA hybridization signal was detected in neurons of several CBS nuclei involved in the control of food intake, including the dorsal vagal complex and parabrachial nucleus. A strong hybridization signal was also obtained from neuronal cell bodies of a number of other structures including the hypoglossal, trigeminal, lateral reticular, and cochlear nuclei; locus ceruleus; and inferior olive. The anatomical profile revealed by fluorescence in situ hybridization was in good agreement with immunocytochemical analysis with an antibody specific to Ob-Rb. In a second experiment, exploring the relevance of CBS Ob-Rb to feeding behavior, rats were given a fourth intracerebroventricular (i.c.v.) injection of leptin (0.1, 0.83, or 5.0 g; n 9 –11/group) or vehicle 30 min before lights-out on three consecutive days The two higher doses reduced food intake significantly at 2, 4, and 24 h after injection and caused significant reductions of body weight. The dose-response profiles for fourth i.c.v. administration were indistinguishable from those obtained from separate groups of rats that received leptin via a lateral i.c.v. cannula. In the last experiment, a ventricle-subthreshold dose of leptin (0.1 g) microinjected unilaterally into the dorsal vagal complex suppressed food intake at 2, 4, and 24 h. The results indicate that the CBS contains neurons that are potentially direct targets for the action of leptin in the control of energy homeostasis. (Endocrinology 143: 239 –246, 2002)
388 citations
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TL;DR: S sensitization of incentive salience can produce addictive behavior even if the expectation of drug pleasure or the aversive properties of withdrawal are diminished and even in the face of strong disincentives, including the loss of reputation, job, home and family.
6,783 citations
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TL;DR: A model is described that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.
Abstract: New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its importance to human health. Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity, the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. To better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food intake and the means by which obesity can arise from inherited or acquired defects in their function.
6,178 citations
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TL;DR: The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
Abstract: Cannon, Barbara, and Jan Nedergaard. Brown Adipose Tissue: Function and Physiological Significance. Physiol Rev 84: 277–359, 2004; 10.1152/physrev.00015.2003.—The function of brown adipose tissue i...
5,470 citations
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TL;DR: It is suggested that dopamine may be more important to incentive salience attributions to the neural representations of reward-related stimuli and is a distinct component of motivation and reward.
3,833 citations
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TL;DR: The authors hypothesize that there is a general bias, based on both innate predispositions and experience, in animals and humans to give greater weight to negative entities (e.g., events, objects, personal traits).
Abstract: We hypothesize that there is a general bias, based on both innate predispositions and experience, in animals and humans, to give greater weight to negative entities (e.g., events, objects, personal traits). This is manifested in 4 ways: (a) negative potency (negative entities are stronger than the equivalent positive entities), (b) steeper nega tive gradients (the negativity of negative events grows more rapidly with approach to them in space or time than does the positivity of positive events, (c) negativity domi nance (combinations of negative and positive entities yield evaluations that are more negative than the algebraic sum of individual subjective valences would predict), and (d) negative differentiation (negative entities are more varied, yield more complex conceptual representations, and engage a wider response repertoire). We review evi dence for this taxonomy, with emphasis on negativity dominance, including literary, historical, religious, and cultural sources, as well as the psychological literatures on learning, attention, impression formation, contagion, moral judgment, development, and memory. We then consider a variety of theoretical accounts for negativity bias. We suggest that 1 feature of negative events that make them dominant is that negative entities are more contagious than positive entities.
3,032 citations