The gut endocrine system is emerging as a central player in the control of appetite and glucose homeostasis, and as a rich source of peptides with therapeutic potential in the field of diabetes and obesity. In this study we have explored the physiology of insulin-like peptide 5 (Insl5), which we identified as a product of colonic enteroendocrine L-cells, better known for their secretion of gluc...

SORCS1 and SORCS3 are two related sorting receptors expressed in neurons of the arcuate nucleus of the hypothalamus. Using mouse models with individual or dual receptor deficiencies, we document a previously unknown function of these receptors in central control of metabolism. Specifically, SORCS1 and SORCS3 act as intracellular trafficking receptors for tropomyosin-related kinase B to attenuat...

Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, plays a major role in inhibiting seizures. However, the underlying mechanism of ghrelin's anticonvulsant action is still unclear. Nowadays, there are considerable evidences showing that ghrelin is implicated in various neurophysiological processes, including learning and memory, neuroprotection, neurogenesis, a...

The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs. We report that orexigenic AAPDs potently and selectively activate hypothalamic AMP-kinase, an action abolished in mice with deletion of histamine H1 receptors. These findings may afford a means of developing more effecti...

Celiac disease is defined as a permanent gluten intolerance, which if untreated leads to malnutrition. The effect of that disease on the gut-brain axis remains unknown. This paper reports the level of plasma ghrelin, orexin A and B in a group of fifteen 8.6 ± 3.4-year-old children with untreated celiac disease and experimentally maintained on a gluten-free diet. A group of 15 age-matched health...

Jerboas are wild rodents exhibiting exceptional adaptation to their desert environment. Under harsh autumn conditions, they shut down reproduction, increase body weight and hibernate, while during spring they become sexually active even under negative energy-balance. We recently reported that these rhythms are associated with synchronized changes in genes expressing reproductive (Kiss1, Rfrp) a...

Intra-uterine growth restriction (IUGR) is involved in developmental metabolic programming and here we test the hypothesis that IUGR affects the developing hypothalamic energy balance regulatory pathways in a sex-specific manner. This experiment investigated early postnatal hypothalamic gene expression for six primary leptin- and insulin-sensitive neuropeptides and receptors in male and female ...

Previous studies have demonstrated that mammalian target of rapamycin (mTOR) signalling in the hypothalamus is involved in the control of energy homeostasis. The aim of this study was to characterize the effect of mTOR signalling in the dorsal motor nucleus of the vagus (DMNV) on energy intake. Phospho-mTOR was detected in the DMNV neurons, and its levels were increased by energy deprivation. R...

Obesity is often attributed to a Western lifestyle, a high-fat diet and decreased activity. While these factors certainly contribute to adult obesity, compelling data from our laboratory and others indicate that this explanation is oversimplified. Recent studies strongly argue that maternal/fetal under- or overnutrition predisposes the offspring to become hyperphagic and increases the risk of l...