Glucose-dependent insulinotropic polypeptide receptor systems in the hypothalamus and the brainstem regulate feeding and weight through distinct pathways.

The report by Adriaenssens et al. in JCI Insight 22 May 2023 explored the role and property of the neurons that express glucose-dependent insulinotropic polypeptide receptor (GIPR) in the brainstem and hypothalamus. The chemogenetic activation of the brainstem GIPR neurons and that of the hypothalamic GIPR neurons showed different feeding and behavior responses.

1,5-Anhydro-D-Fructose Exhibits Satiety Effects via the Activation of Oxytocin Neurons in the Paraventricular Nucleus.

1,5-Anhydro-D-fructose (1,5-AF) is a bioactive monosaccharide that is produced by the glycogenolysis in mammalians and is metabolized to 1,5-anhydro-D-glucitol (1,5-AG). 1,5-AG is used as a marker of glycemic control in diabetes patients. 1,5-AF has a variety of physiological activities, but its effects on energy metabolism, including feeding behavior, are unclarified.

Glucose-dependent insulinotropic polypeptide counteracts diet-induced obesity along with reduced feeding, elevated plasma leptin and activation of leptin-responsive and proopiomelanocortin neurons in the arcuate nucleus.

Aim: To clarify the effects of glucose-dependent insulinotropic polypeptide (GIP) receptor agonists (GIPRAs) on feeding and body weight.

Materials And Methods: Acute and subchronic effects of subcutaneous GIPFA-085, a long-acting GIPRA, on blood glucose, food intake, body weight, respiratory exchange ratio and plasma leptin levels were measured in diet-induced obese (DIO) mice and/or functional leptin-deficient ob/ob mice. The effects of GIPFA-085 on the hypothalamic arcuate nucleus (ARC) neurons from lean and DIO mice were studied by measuring cytosolic Ca concentration ([Ca ] ).

Fasting inhibits excitatory synaptic input on paraventricular oxytocin neurons neuropeptide Y and Y1 receptor, inducing rebound hyperphagia, and weight gain.

Fasting with varying intensities is used to treat obesity-related diseases. Re-feeding after fasting exhibits hyperphagia and often rebound weight gain. However, the mechanisms underlying the hyperphagia and rebound remain elusive.

d-Allulose Inhibits Ghrelin-Responsive, Glucose-Sensitive and Neuropeptide Y Neurons in the Arcuate Nucleus and Central Injection Suppresses Appetite-Associated Food Intake in Mice.

d-allulose, a rare sugar, has sweetness with few calories. d-allulose regulates feeding and glycemia, and ameliorates hyperphagia, obesity and diabetes. All these functions involve the central nervous system.

TRPV1-Mediated Sensing of Sodium and Osmotic Pressure in POMC Neurons in the Arcuate Nucleus of the Hypothalamus.

The central melanocortin system conducted by anorexigenic pro-opiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus (ARC) not only regulates feeding behavior but also blood pressure. Excessive salt intake raises the Na concentration ([Na]) in the cerebrospinal fluid (CSF) and worsens hypertension. The blood-brain barrier is immature in the ARC.

D-Allulose cooperates with glucagon-like peptide-1 and activates proopiomelanocortin neurons in the arcuate nucleus and central injection inhibits feeding in mice.

A rare sugar D-Allulose has sweetness without calorie. Previous studies have shown that D-Allulose improves glucose and energy metabolism and ameliorates obesity. However, underlying mechanisms remain elusive.

Coexistence of sensory qualities and value representations in human orbitofrontal cortex.

Despite the multiple regions and neural networks associated with value-based decision-making, the orbitofrontal cortex (OFC) is possible a particularly important one. Although the role of the OFC in reinforcer devaluation tasks, which assess the ability to represent identity, sensory qualities, and subjective values of the expected outcomes, has been established, the specific aspect represented in this area remains unclear. In this study, using functional magnetic resonance imaging, wherein participants rated the palatability of 128 food items using photographs, we investigated whether the human OFC represents object identity, sensory qualities, or value.

Circadian Clock Component BMAL1 in the Paraventricular Nucleus Regulates Glucose Metabolism.

It is suggested that clock genes link the circadian rhythm to glucose and lipid metabolism. In this study, we explored the role of the clock gene in the hypothalamic paraventricular nucleus (PVN) in glucose metabolism. The --mediated deletion of markedly reduced insulin secretion, resulting in impaired glucose tolerance.

Status of ghrelin as an islet hormone and paracrine/autocrine regulator of insulin secretion.

Ghrelin is expressed in the pancreatic islet cells as well as the stomach. In the perfused pancreas and isolated islets, GHS-R antagonism, ghrelin immunoneutralization and ghrelin-knockout (Ghr-KO) all increase glucose-induced insulin release. Thus, pharmacological, immunological and genetic blockades of ghrelin in the pancreatic islets all markedly augment glucose-induced insulin release, showing that islet-derived ghrelin physiologically restricts insulin release in rodents.

Onion component, isoalliin, stimulates feeding and activates the arcuate nucleus neuropeptide Y, ghrelin- and Ninjin'yoeito-responsive neurons.

Appetite loss or anorexia substantially decreases the quality of life in patients with cancer, depression and gastrointestinal disorders, and can lead to sarcopenia and frailty. Foods that restore appetite have been sought-for but are not currently available. Historically, onion intake was adopted to treat a variety of diseases with reduced appetite including cancer and gastrointestinal disturbances.

Gastrointestinal Distension by Pectin-Containing Carbonated Solution Suppresses Food Intake and Enhances Glucose Tolerance GLP-1 Secretion and Vagal Afferent Activation.

Diet-induced gastrointestinal distension is known to evoke satiation and suppress postprandial hyperglycemia; however, the underlying mechanisms remain poorly understood. This study explored how gastrointestinal distension regulates energy homeostasis by using inflating stomach formulation (ISF), the carbonated solution containing pectin that forms stable gel bubbles under acidic condition in the stomach. Here we show that, in mice, oral administration of ISF induced distension of stomach and proximal intestine temporarily, stimulated intestinal glucagon-like peptide-1 (GLP-1) secretion, and activated vagal afferents and brainstem.

Ninjin'yoeito Targets Distinct Ca Channels to Activate Ghrelin-Responsive vs. Unresponsive NPY Neurons in the Arcuate Nucleus.

Appetite loss or anorexia substantially deteriorates quality of life in various diseases, and stand upstream of frailty. Neuropeptide Y (NPY) in the hypothalamic arcuate nucleus (ARC) and ghrelin released from stomach are potent inducers of appetite. We previously reported that Ninjin'yoeito, a Japanese kampo medicine comprising twelve herbs, restores food intake, and body weight in cisplatin-treated anorectic mice.

Lavender Oil Reduces Depressive Mood in Healthy Individuals and Enhances the Activity of Single Oxytocin Neurons of the Hypothalamus Isolated from Mice: A Preliminary Study.

Background: The aim of the present study was to assess the effects of lavender oil inhalation on blood pressure, pulse measurements, cortisol levels, depressive mood, and anxiety in healthy male adults. The mechanism was investigated by the action on oxytocin single neurons in the hypothalamus of rodents.

Methods: The participants ( = 7) were aged 20-40 years.

Peripheral circadian rhythms in the liver and white adipose tissue of mice are attenuated by constant light and restored by time-restricted feeding.

Disturbance of circadian rhythms underlies various metabolic diseases. Constant light exposure (LL) is known to disrupt both central and peripheral circadian rhythms. Here, we attempted to determine whether the effects of LL are different between various peripheral tissues and whether time-restricted feeding restores the circadian rhythms especially in white adipose tissue (WAT).

Immunohistochemical localization and possible functions of nesfatin-1 in the testis of mice during pubertal development and sexual maturation.

The study was aimed to address the role of nesfatin-1 on the sexual maturation of testis during the pubertal transition. The immunostaining of testis suggested nesfatin-1 is expressed in Leydig cells with pubertal maturation. The pre-pubertal mice for in vivo study were randomly divided in three groups; (a) control-saline (b) treated with low (0.

Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats.

Glucagon-like peptide-1 receptor (GLP-1R) agonists, widely used to treat type 2 diabetes, reduce blood pressure (BP) in hypertensive patients. Whether this action involves central mechanisms is unknown. We here report that repeated lateral ventricular (LV) injection of GLP-1R agonist, liraglutide, once daily for 15 days counteracted the development of hypertension in spontaneously hypertensive rats (SHR).

Relay of peripheral oxytocin to central oxytocin neurons via vagal afferents for regulating feeding.

Oxytocin (Oxt), a neurohormone synthesized in the neurons of hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus induces milk-ejection and uterine contraction and regulates social behavior, stress responses, memory and food intake. Peripheral (intraperitoneal and subcutaneous) infusion of Oxt decreases food intake and body weight in obese animals via mechanisms involving vagal afferent nerves and in obese subjects when administered nasally. Peripherally injected and intracerebroventricularly injected Oxt inhibit food intake to similar extent and with similar time course.

Islet β-cell-produced NUCB2/nesfatin-1 maintains insulin secretion and glycemia along with suppressing UCP-2 in β-cells.

Nesfatin-1 is a hypothalamic anorexigenic peptide processed from nucleobindin 2 (NUCB2). Central and peripheral administration of NUCB2/nesfatin-1 enhances glucose metabolism and insulin release. NUCB2/nesfatin-1 is also localized in pancreatic islets, while its function remains unknown.

Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice.

Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius.

Ninjin-yoeito activates ghrelin-responsive and unresponsive NPY neurons in the arcuate nucleus and counteracts cisplatin-induced anorexia.

Reduced appetite or anorexia substantially deteriorates quality of life in various diseases including cancer, depression and heart failure. Furthermore, reduced appetite may stand upstream of sarcopenia and frailty. All these diseases are heavy burdens in the modern medicine and society.

Direct effects of neuropeptide nesfatin-1 on testicular spermatogenesis and steroidogenesis of the adult mice.

Recent studies have revealed nesfatin-1 as a hypothalamic neuropeptide, regulating food intake, energy expenditure and reproduction primarily by acting on the hypothalamic-pituitary-gonadal axis. Nesfatin-1 is also localized in several peripheral tissues including testes. However, functional significance of nesfatin-1 in testicular activities is not yet well documented in mammals.

New insight into GABAergic neurons in the hypothalamic feeding regulation.

Several lines of study have suggested that GABA in the hypothalamic feeding center plays a role in promoting food intake. Recent studies revealed that not only NPY/AgRP neurons in the hypothalamic arcuate nucleus (ARC) that co-express GABA but also other GABAergic neurons act as an orexigenic. Here, we review the progress of studies on hypothalamic GABAergic neurons distributed in ARC, dorsomedial hypothalamus (DMH), and lateral hypothalamus (LH).