GHS-R1a deficiency mitigates lipopolysaccharide-induced lung injury in mice via the downregulation of macrophage activity.

Acute respiratory distress syndrome (ARDS) is a critical illness syndrome characterized by dysregulated pulmonary inflammation. Currently, effective pharmacological treatments for ARDS are unavailable. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor type 1a (GHS-R1a), has a pivotal role in regulating energy metabolism and immunomodulation.

Functional interaction between Ghrelin and GLP-1 regulates feeding through the vagal afferent system.

The gastrointestinal tract transmits feeding-regulatory signals to the brain via neuronal and hormonal pathways. Here we studied the interaction between the orexigenic gastric peptide, ghrelin, and the anorectic intestinal peptide, glucagon-like peptide 1 (GLP-1), in terms of feeding regulation via the vagal afferents. GLP-1 preadministration 30 min before ghrelin administration to rats and mice abolished ghrelin-induced food intake, while ghrelin preadministration abolished the anorectic effect of GLP-1.

Analysis of peripheral ghrelin signaling via the vagus nerve in ghrelin receptor-restored GHSR-null mice.

The vagus nerve connects peripheral organs to the central nervous system (CNS), and gastrointestinal hormones transmit their signals to the CNS via the vagal afferent nerve. Ghrelin, a gastric-derived orexigenic peptide, stimulates food intake by transmitting starvation signals via the vagus nerve. To understand peripheral ghrelin signaling via the vagus nerve, we investigated the ghrelin receptor (GHSR)-null mouse.

Restoration of metabolic inflammation-related ghrelin resistance by weight loss.

High-fat diet (HFD)-induced metabolic inflammation in the central and peripheral organs contributes to the pathogenesis of obesity. Long-term HFD blunts signaling by ghrelin, a gastric-derived orexigenic peptide, in the vagal afferent nerve via a mechanism involving activation of inflammation. This study was undertaken to investigate whether ghrelin resistance is associated with progressive development of metabolic inflammation.

NERP-2 regulates gastric acid secretion and gastric emptying via the orexin pathway.

Neuroendocrine regulatory peptide (NERP)-2 is derived from a distinct region of VGF, a neurosecretory protein originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. Colocalization of NERP-2 with orexin-A in the lateral hypothalamus increases orexin-A-induced feeding and energy expenditure in both rats and mice. Orexigenic and anorectic peptides in the hypothalamus modulate gastric function.

Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic Vagal Activation via the Nicotinic Alpha 7 Acetylcholine Receptor.

Central insulin action activates hepatic IL-6/STAT3 signaling, which suppresses the gene expression of hepatic gluconeogenic enzymes. The vagus nerve plays an important role in this centrally mediated hepatic response; however, the precise mechanism underlying this brain-liver interaction is unclear. Here, we present our findings that the vagus nerve suppresses hepatic IL-6/STAT3 signaling via α7-nicotinic acetylcholine receptors (α7-nAchR) on Kupffer cells, and that central insulin action activates hepatic IL-6/STAT3 signaling by suppressing vagal activity.

One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice.

A high-fat diet (HFD) induces inflammation in systemic organs including the hypothalamus, resulting in obesity and diabetes. The vagus nerve connects the visceral organs and central nervous system, and the gastric-derived orexigenic peptide ghrelin transmits its starvation signals to the hypothalamus via the vagal afferent nerve. Here we investigated the inflammatory response in vagal afferent neurons and the hypothalamus in mice following one day of HFD feeding.

Diet-induced obesity causes peripheral and central ghrelin resistance by promoting inflammation.

Ghrelin, a stomach-derived orexigenic peptide, transmits starvation signals to the hypothalamus via the vagus afferent nerve. Peripheral administration of ghrelin does not induce food intake in high fat diet (HFD)-induced obese mice. We investigated whether this ghrelin resistance was caused by dysfunction of the vagus afferent pathway.

Neuroendocrine regulatory peptide-1 and -2 (NERPs) inhibit the excitability of magnocellular neurosecretory cells in the hypothalamus.

Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 (NERPs) are novel carboxy-terminally amidated peptides derived from the neurosecretory protein VGF. NERPs are colocalized with vasopressin in the paraventricular nucleus (PVN) and the supraoptic nucleus (SON) of the hypothalamus, and suppress vasopressin secretion evoked by intracerebroventricular administration of angiotensin II (AngII) and hypertonic saline or bath administration of AngII. Magnocellular neurosecretory cells (MCNs) of the hypothalamus release vasopressin and oxytocin from their dendrites and soma.

Circulating des-acyl ghrelin improves cardiovascular risk prediction in older hypertensive patients.

Background: We aimed to assess the predictive value of circulating levels of des-acyl ghrelin, an abundant form of ghrelin in humans, for the risk of cardiovascular disease (CVD) in older hypertensive patients. We simultaneously evaluated other biomarkers, such as high-molecular-weight (HMW) adiponectin, high-sensitivity C-reactive protein (hs-CRP), and plasminogen activator inhibitor 1 (PAI-1), for their usefulness in risk prediction.

Methods: We enrolled 590 older hypertensive patients (mean age = 72.

Elevation of muscle temperature stimulates muscle glucose uptake in vivo and in vitro.

The purpose of this study was to examine whether elevation of muscle temperature per se might be a stimulatory factor to increase muscle glucose uptake. Heat stimulation to rat hindlimbs increased glucose uptake measured in vivo in the extensor digitorum longus (EDL) and soleus muscles with a significant increase in muscle temperature. This thermal effect was observed again when glucose uptake was measured in vitro in both isolated muscles immediately after the heat stimulation in vivo.

Ghrelin prevents the development of experimental diabetic neuropathy in rodents.

Ghrelin is an acylated peptide discovered in gastric extracts as an endogenous ligand for the growth hormone secretagogue (GHS) receptor. This peptide increases food intake and growth hormone secretion, suppresses inflammation and oxidative stress, and promotes cell survival and proliferation. Our study investigated the pharmacological effect of ghrelin in the prevention of polyneuropathy in streptozotocin-induced diabetes mellitus in C57BL/6N mice, GHS receptor-deficient mice, and growth hormone-deficient rats.

Neuroendocrine regulatory peptide-2 stimulates glucose-induced insulin secretion in vivo and in vitro.

Neuroendocrine regulatory peptide (NERP)-2, recently identified as a bioactive peptide involved in vasopressin secretion and feeding regulation in the central nervous system, is abundantly expressed in endocrine cells in peripheral tissues. To explore the physiological roles of NERP-2 in the pancreas, we examined its effects on insulin secretion. NERP-2 increased glucose-stimulated insulin secretion (GSIS) in a dose-dependent manner, with a lowest effective dose of 10(-7) M, from the pancreatic β-cell line MIN6 and isolated mouse pancreatic islets.

Therapeutic potential of ghrelin treatment for unloading-induced muscle atrophy in mice.

Ghrelin is a growth hormone (GH) secretagogue secreted mainly from the stomach that functions in controlling muscle volume and energy homeostasis. We here studied the effects of ghrelin on unloading-induced muscle atrophy using a mouse model of hindlimb suspension (HS). Ghrelin administration during 2-week HS alleviated reductions of muscle mass in the fast-twitch fiber-rich plantaris muscle and the slow-twitch fiber-rich soleus muscle of the hindlimb.

Telmisartan suppresses food intake in mice via the melanocortin pathway.

Telmisartan, an angiotensin type 1 receptor blocker, is widely used for the treatment of hypertension and related cardiovascular and organ damage. We here describe the effects of telmisartan on food intake and body weight using C57BL/6N mice, KKAy mice that overexpress agouti protein (a mouse model of type 2 diabetes with obesity), and mice deficient for angiotensin II-1a receptor. Telmisartan combined with a high-fat diet significantly reduced food intake and body weight gain in the three groups of mice compared with respective control animals that were fed the high-fat diet without telmisartan.

Significant lowering of plasma ghrelin but not des-acyl ghrelin in response to acute exercise in men.

Ghrelin, an acylated peptide produced predominantly in the stomach, stimulates feeding and growth hormone (GH) secretion via interaction with the GH secretagogue receptor. Ghrelin molecules are present in two major endogenous forms, an acylated form (ghrelin) and a des-acylated form (des-acyl ghrelin). Recent studies indicated that aerobic exercise did not change plasma total ghrelin levels, however, dynamics of circulating ghrelin and des-acyl ghrelin during aerobic exercise remains unclear.

Neuroendocrine regulatory peptide-2 regulates feeding behavior via the orexin system in the hypothalamus.

Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 are derived from distinct regions of VGF, a neurosecretory protein. Vgf(-/-) mice exhibit dwarfism and hypermetabolic rates, suggesting that VGF or VGF-derived peptides play important roles in energy metabolism. Here, we examined the role of NERPs in the central regulation of feeding and energy homeostasis.

Plasma des-acyl ghrelin, but not plasma HMW adiponectin, is a useful cardiometabolic marker for predicting atherosclerosis in elderly hypertensive patients.

Objective: The coming obesity epidemic in elderly persons necessitates the establishment of new and easy-to-use cardiometabolic markers to identify individuals most likely to develop atherosclerosis among hypertensives.

Methods: We measured plasma HMW adiponectin and des-acyl ghrelin levels, and carotid-artery intima-media thickness (cIMT) in 263 elderly hypertensives (mean 72.6 years; 37%men).

Characterization of obestatin in rat and human stomach and plasma, and its lack of acute effect on feeding behavior in rodents.

Obestatin is a 23-amino acid peptide, initially isolated from rat stomach as an endogenous ligand for the orphan G-protein-coupled receptor. Obestatin is derived from proteolytic cleavage of a 117-amino acid precursor, preproghrelin. Ghrelin increases food intake, body weight, and gastric emptying, whereas obestatin has the opposite effects.

The vagal afferent pathway does not play a major role in the induction of satiety by intestinal fatty acid in rats.

Intestinal infusion of long-chain fatty acids (LCFAs) strongly suppresses food intake and gut motility. Vagal afferents and cholecystokinin (CCK) signaling pathway are considered to play important roles in intestinal LCFA-induced satiety. Here, we first investigated the influence of vagus nerve on satiety following intestinal LCFA infusion in rats.

Ontogeny of a new enteric peptide, neuropeptide W (NPW), in the developing rat stomach.

Neuropeptide W (NPW), a novel endogenous peptide for G protein-coupled receptors GPR7 and GPR8, is expressed in the gastric antral mucosa of rat, mouse, and human stomachs. Here, we studied the ontogeny of NPW in the developing rat stomach. Real-time RT-PCR showed that NPW gene expression was initially detectable in embryonic day 14 (E14) stomach and gradually increased during the progress of age until birth, postnatal day 1 (P1).

[Hormone replacement Up-to-date. Ghrelin, growth hormone and somatopause].

Age-related decreases in energy expenditure and physical activity have been associated with the loss of skeletal muscle and decline of food intake, possibly through a mechanism involving changes of growth hormone secretion and feeding behavior. Age-related declines of growth hormone secretion and food intake have been termed the somatopause and anorexia of aging, respectively. Ghrelin was isolated from human and rat stomachs as an endogenous ligand of growth hormone secretagogue receptor.

Peptidomic identification and biological validation of neuroendocrine regulatory peptide-1 and -2.

Recent advances in peptidomics have enabled the identification of previously uncharacterized peptides. However, sequence information alone does not allow us to identify candidates for bioactive peptides. To increase an opportunity to discover bioactive peptides, we have focused on C-terminal amidation, a post-translational modification shared by many bioactive peptides.

Ghrelin stimulates growth hormone secretion and food intake in aged rats.

Age-related decreases in energy expenditure have been associated with the loss of skeletal muscle and decline of food intake, possibly through a mechanism involving changes of growth hormone (GH) secretion and feeding behavior. Age-related declines of growth hormone secretion and food intake have been termed the somatopause and anorexia of ageing, respectively. Ghrelin, a 28-amino-acid peptide, was isolated from human and rat stomachs as an endogenous ligand of growth hormone secretagogue receptor.