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Abstract

In recent years, knowledge about hormonal feedback from the gastrointestinal tract and adipose tissue has increased tremendously. Peptide hormones modulating hunger have been intensively studied, mostly in animals but increasingly also in humans. The first therapeutic agents, such as GLP-1 analogues, are in successful clinical use for T2D and may beneficially affect hunger and reduce weight. Data from in vitro studies and animals provide detailed insight into regulatory mechanisms leading to peptide secretion and receptor bindings, as well as to the distribution of receptors involved in different parts of the body. With neuroimaging techniques human brain structures have been identified that play a role in hunger, satiety and eating behaviour. These include the primary gustatory (insular) and olfactory (pyriform) cortex and regions with a highly permeable blood-brain barrier (hypothalamus, brain stem), which facilitates humoral input via gut peptides and leptin. In addition, cerebral networks involved in higher cognitive functions, especially those relevant to reward, pleasure and also addiction (ventral and dorsal striatum, amygdala, orbitofrontal cortex (OFC), prefrontal cortex (PFC)) were shown to be involved. First indications of direct influences of peptide hormones on these networks have become available from neuroimaging studies administrating synthetic PYY, ghrelin and leptin. Insulin also appears to play an important role as a central satiety hormone, and evidence indicating the possibility of central insulin resistance in obesity is available.