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Ghrelin induces adiposity in rodents
It is proposed that ghrelin, in addition to its role in regulating GH secretion, signals the hypothalamus when an increase in metabolic efficiency is necessary, suggesting an involvement in regulation of energy balance.
Obesity is associated with hypothalamic injury in rodents and humans.
Obesity is associated with neuronal injury in a brain area crucial for body weight control in both humans and rodent models, and evidence of increased gliosis in the mediobasal hypothalamus of obese humans is found.
The Distribution and Mechanism of Action of Ghrelin in the CNS Demonstrates a Novel Hypothalamic Circuit Regulating Energy Homeostasis
Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite.
It is shown 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, suggesting that the mesolimbic reward circuitry is targeted by peripheral gh Relin to influence physiological mechanisms related to feeding.
The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis.
It is shown that the lack of CB1 in mice with a disrupted CB1 gene causes hypophagia and leanness, and the cannabinoid system is an essential endogenous regulator of energy homeostasis via central orexigenic as well as peripheral lipogenic mechanisms and might therefore represent a promising target to treat diseases characterized by impaired energy balance.
Circulating ghrelin levels are decreased in human obesity.
- M. Tschöp, C. Weyer, P. Tataranni, V. Devanarayan, E. Ravussin, M. Heiman
- Medicine, BiologyDiabetes
- 1 April 2001
Plasma ghrelin concentration was decreased in obese Caucasians as compared with lean Caucasians and was lower in Pima Indians, a population with a very high prevalence of obesity, compared with Caucasians.
Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin.
Ghrelin is considered a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis and there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.
Sirt1 protects against high-fat diet-induced metabolic damage
- P. Pfluger, D. Herranz, S. Velasco-Miguel, M. Serrano, M. Tschöp
- BiologyProceedings of the National Academy of Sciences
- 15 July 2008
Data is presented indicating that beneficial effects of Sirt1 are due to at least two mechanisms: induction of antioxidant proteins MnSOD and Nrf1, possibly via stimulation of PGC1α, and lower activation of proinflammatory cytokines, such as TNFα and IL-6, via down-modulation of NFκB activity.
Ghrelin controls hippocampal spine synapse density and memory performance
It is reported that circulating ghrelin enters the hippocampus and binds to neurons of the hippocampal formation, where it promotes dendritic spine synapse formation and generation of long-term potentiation.
Extent and Direction of Ghrelin Transport Across the Blood-Brain Barrier Is Determined by Its Unique Primary Structure
- W. Banks, M. Tschöp, S. M. Robinson, M. Heiman
- BiologyJournal of Pharmacology and Experimental…
- 1 August 2002
It is shown that ghrelin transport across the blood-brain barrier is a complex, highly regulated bidirectional process, defining a new role for the unique post-translational octanoylation.