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Start Over Author "Sleeman MW" Journal journal of clinical investigation
2 results on '"Sleeman MW"'

1. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite.

Author

Abizaid A, Liu ZW, Andrews ZB, Shanabrough M, Borok E, Elsworth JD, Roth RH, Sleeman MW, Picciotto MR, Tschöp MH, Gao XB, and Horvath TL

Subjects
Action Potentials drug effects, Animals, Fluorescent Antibody Technique methods, Ghrelin, Male, Mesencephalon cytology, Mesencephalon drug effects, Mesencephalon metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons drug effects, Neurons physiology, Nucleus Accumbens cytology, Nucleus Accumbens drug effects, Nucleus Accumbens metabolism, Patch-Clamp Techniques, Peptide Hormones metabolism, Rats, Rats, Sprague-Dawley, Receptors, G-Protein-Coupled metabolism, Receptors, Ghrelin, Time Factors, Ventral Tegmental Area cytology, Ventral Tegmental Area drug effects, Ventral Tegmental Area metabolism, Appetite drug effects, Dopamine metabolism, Neurons metabolism, Peptide Hormones pharmacology
Abstract

The gut hormone ghrelin targets the brain to promote food intake and adiposity. The ghrelin receptor growth hormone secretagogue 1 receptor (GHSR) is present in hypothalamic centers controlling energy metabolism as well as in the ventral tegmental area (VTA), a region important for motivational aspects of multiple behaviors, including feeding. Here we show that in mice and rats, ghrelin bound to neurons of the VTA, where it triggered increased dopamine neuronal activity, synapse formation, and dopamine turnover in the nucleus accumbens in a GHSR-dependent manner. Direct VTA administration of ghrelin also triggered feeding, while intra-VTA delivery of a selective GHSR antagonist blocked the orexigenic effect of circulating ghrelin and blunted rebound feeding following fasting. In addition, ghrelin- and GHSR-deficient mice showed attenuated feeding responses to restricted feeding schedules. Taken together, these data suggest that the mesolimbic reward circuitry is targeted by peripheral ghrelin to influence physiological mechanisms related to feeding.

Published
2006
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2. Absence of ghrelin protects against early-onset obesity.

Author

Wortley KE, del Rincon JP, Murray JD, Garcia K, Iida K, Thorner MO, and Sleeman MW

Subjects
Animal Feed, Animals, Body Composition, Body Weight, Calorimetry, Carbohydrates chemistry, Diet, Genotype, Ghrelin, Growth Hormone metabolism, Heterozygote, Insulin-Like Growth Factor I metabolism, Ligands, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Biological, Neuropeptides chemistry, Oxygen metabolism, Peptide Hormones metabolism, Phenotype, Pituitary Gland metabolism, RNA, Messenger metabolism, Reverse Transcriptase Polymerase Chain Reaction, Time Factors, Obesity genetics, Peptide Hormones physiology
Abstract

The gut peptide ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, has been implicated not only in the regulation of pituitary growth hormone (GH) secretion but in a number of endocrine and nonendocrine functions, including appetitive behavior and carbohydrate substrate utilization. Nevertheless, recent genetic studies have failed to show any significant defects in GH levels, food intake, or body weight in adult ghrelin-deficient (Ghrl-/-) mice. Here we demonstrate that male Ghrl-/- mice are protected from the rapid weight gain induced by early exposure to a high-fat diet 3 weeks after weaning (6 weeks of age). This reduced weight gain was associated with decreased adiposity and increased energy expenditure and locomotor activity as the animals aged. Despite the absence of ghrelin, these Ghrl-/- mice showed a paradoxical preservation of the GH/IGF-1 axis, similar to that reported in lean compared with obese humans. These findings suggest an important role for endogenous ghrelin in the metabolic adaptation to nutrient availability.

Published
2005
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