The social problems and medical burdens caused by obesity have become more serious in recent years. Obesity is mainly caused by the imbalance of energy intake and consumption in the body. The central nervous system and related neurons regulate the balance of energy metabolism. The hypothalamic arcuate nucleus (ARC) contains anorexigenic proopiomelanocortin (POMC) neurons and orexigenic neuropeptid Y(NPY)/agouti-related protein (AgRP) neurons that regulate the feeding behavior of body. High-fat diet induces phosphorylation of Rb protein in POMC neurons, and inactivation of Rb phosphorylation leads to re-entry of POMC neurons from the resting-state into the cell cycle, which rapidly shifts to apoptosis. High-fat diet also causes the inhibition of neuronal regeneration, induces inflammation and neuronal damage, loss of neuronal homeostasis, leptin resistance, and ultimately leads to obesity. This review discusses the relationship between loss of neuronal homeostasis and dietary obesity, as well as the underlying mechanisms, which might provide the evidence for prevention and treatment of these diseases.
Arcuate Nucleus of Hypothalamus ; Homeostasis ; Humans ; Leptin ; Obesity ; Pro-Opiomelanocortin

Olfaction and food intake are interrelated and regulated. In the process of feeding, the metabolic signals in the body and the feeding signals produced by food stimulation are first sensed by the arcuate nucleus of hypothalamus and the nucleus tractus solitarius of brain stem, and then these neurons project to the paraventricular nucleus of hypothalamus. The paraventricular nucleus transmits the signals to other brain regions related to feeding and regulates feeding behavior. In this process, olfactory signals can be transmitted to hypothalamus through olfactory bulb and olfactory cortex to regulate feeding behavior. At the same time, gastrointestinal hormones (ghrelin, insulin, leptin, etc.) and some neurotransmitters (acetylcholine, norepinephrine, serotonin, endocannabinoid, etc.) produced in the process of feeding act on the olfactory system to regulate olfactory function, which in turn affects the feeding itself. This review summaries the research progress of the interaction between olfaction and food intake and its internal mechanism from the aspects of neuronal and hormonal regulation.
Arcuate Nucleus of Hypothalamus/metabolism* ; Feeding Behavior/physiology* ; Hypothalamus ; Paraventricular Hypothalamic Nucleus ; Smell

The distributions and morphological characteristics of neurons displaying immunoreactivity to the catecholamine synthetic enzymes, tyrosine hydroxylase[TH], dopamine-beta-hydroxylase[DBH], and phenyletha-nolamine-N-methyltransferase[PNMT] were examined in the adjacent sections of the diencephalon of the striped field mouse [Apodemus agrarius coreae].Only TH-, and no DBH- or PNMT-immunoreactive neurons were found in the diencephalon. In the preoptic area, TH-immunoreactive neurons were found in the anterior preoptic nucleus of Loo[APN], periventricular preoptic nucleus, medial preoptic nucleus, lateral preoptic nucleus and suprachiasmatic nucleus. In the hypothalamus, TH-immunoreactive neurons were found in theparaventricular hypothalamic nucleus, periventricular gray, retrochiasmatic area,anterior hypothalamic nucleus of anterior hypothalamic area and retrochiasmatic region of the hypothalamus. In the rostral tuberal region of the hypothalamus, TH-immunoreactive neurons were found in the paraventricular nucleus, periventricular gray and arcuate nucleus. In the midtuberal region of the hypothalamus, TH-immunoreactive neurons were found in the paraventricular nucleus, dorsomedial hypothalamic nucleus, zona incerta and arcuate nucleus. In the caudal tuberal region of the hypothalamus, dorsal hypothalamic nucleus, posterior hypothalamic complex and arcuate nucleus.
Animals ; Anterior Hypothalamic Nucleus ; Arcuate Nucleus ; Diencephalon* ; Dopaminergic Neurons* ; Dorsomedial Hypothalamic Nucleus ; Hypothalamus ; Immunohistochemistry ; Mice ; Neurons ; Paraventricular Hypothalamic Nucleus ; Preoptic Area ; Subthalamus ; Suprachiasmatic Nucleus ; Tyrosine

The present study was aimed to explore the effects of intraperitoneal injection of growth hormone releasing peptide-6 (GHRP-6), a ghrelin receptor agonist, on food intake and neuronal activity of feeding-related nuclei in the hypothalamus of NMRI mice. Accumulated amount of food intake was measured, and total number of c-fos immunoreactive neurons in arcuate nucleus (ARC), paraventricular nucleus (PVN) and supraoptic nucleus (SON) was counted by immunohistochemistry at 1, 3 and 6 h after the GHRP-6 injection. The results showed that GHRP-6 significantly increased the amount of food intake with a peak at 3 h after the GHRP-6 injection. Meanwhile, GHRP-6 could promote c-fos expression in the ARC and PVN independent of food intake, and the total number of c-fos immunoreactive neurons was peaked at 1 h after injection and then decreased gradually. These results suggest that GHRP-6 may increase food intake in time-dependent manner, which is associated with up-regulations of c-fos protein expression in the ARC and PVN.
Animals ; Arcuate Nucleus of Hypothalamus ; Eating ; Immunohistochemistry ; Male ; Mice ; Neurons ; Oligopeptides ; Paraventricular Hypothalamic Nucleus ; Proto-Oncogene Proteins c-fos ; Receptors, Ghrelin ; Supraoptic Nucleus

This study investigated the interrelation between the hypothalamic arcuate nucleus (ARC) and the bone variation of osteoporosis in rats. Four animal models of ovariectomy-induced osteoporosis (OVX), glucocorticoid-induced osteoporosis (GIOP), retinoic acid-induced osteoporosis (RAOP) and senile osteoporosis (SOP) were used to study the influence of osteoporosis on ARC. Ovariectomized rats were further treated with thymopeptide, ciclosporin and exercise respectively to detect the changes of ARC nerve cells number. The results showed that: (1) The OVX, GIOP, RAOP and SOP models were successfully established, showing osteoporosis as well as decrease of the number of ARC nerve cells; (2) Thymopeptide and exercise respectively alleviated the bone loss induced by ovariectomy, accompanied by increase of the number of ARC nerve cells, while ciclosporin further increased the bone loss of ovariectomized rats, accompanied by further decrease of the number of ARC nerve cells. These results suggest that there is a close interrelationship between ARC and osteoporosis in rat. There is a hypothalamus-pituitary-bone (HPB) axis, and HPB axis regulates the mechanism of osteoporosis in rats.
Animals ; Arcuate Nucleus of Hypothalamus ; physiopathology ; Bone and Bones ; physiopathology ; Disease Models, Animal ; Female ; Osteoporosis ; chemically induced ; pathology ; Ovariectomy ; Rats

This study was conducted to define the underlying mechanism of hypophagia induced by increased central serotonergic action. Rats received 3 daily injections of 5-hydroxy-L-tryptophan (5-HTP), a serotonin precursor, at a dose of 100 mg/kg/10 ml saline at 1 h before lights off. A significant suppression in food intake was observed shortly after the 5-HTP injection and persisted during 3 daily 5-HTP injections. Neuropeptide Y (NPY) expression in the arcuate nucleus increased after 3 days of 5-HTP treatment, as high as in the pair-fed group. Immunoreactivity of phosphorylated extracellular signal-regulated protein kinase (pERK1/2) in the hypothalamic paraventricular nucleus (PVN) was increased markedly by 3 days of 5-HTP treatment, but not by 3 days of pair-fed. mRNA expression levels of serotonin reuptake transporter (5-HTT) was increased in the dorsal raphe nucleus of the 5-HTP treated rats, but not in the pair-fed group. Results suggest that increased pERK1/2 in the PVN of 5-HTP injected rats may be a part of serotonergic anorectic signaling, perhaps blunting the orectic action of NPY; i.e., 5-HTP injected rats showed hypophagia despite of increased NPY expression in the arcuate nucleus.
5-Hydroxytryptophan ; Animals ; Arcuate Nucleus ; Eating ; Hypothalamus ; Light ; Neuropeptide Y ; Paraventricular Hypothalamic Nucleus ; Protein Kinases ; Raphe Nuclei ; Rats ; RNA, Messenger ; Serotonin

BDNF belongs to the neurotrophin family and important molecular mediator of functional and structural plasticity. The highest levels of BDNF are found in the hippocampus and hypothalamus of the adult rat. Hypothalamus is important because of its high degree of plasticity, but little is known about distribution of BDNF in hypothalamic nuclei. Therefore, it is necessary to study distribution and expression pattern of BDNF in each hypothalamic nuclei to understand changes of BDNF through various neural damages including spinal cord injury. Through this experiment, we found specific BDNF expression pattern in some regions of hypothalamus and the results are as follows. 1) BDNF expressions were found in median eminence, arcuate nucleus, supraoptic nucleus, and periventricular nucleus of rat hypothalamus. 2) BDNF immunoreactive cells and nerve fibers were of various shapes and sizes. 3) Glial cells also express BDNF in certain hypothalamic nuclei. These results seem to be useful for future investigations of neurochemical changes in the hypothalamus induced by various neural trauma or degenerative changes
Adult ; Animals ; Arcuate Nucleus ; Brain-Derived Neurotrophic Factor ; Hippocampus ; Humans ; Hypothalamus ; Median Eminence ; Nerve Fibers ; Neuroglia ; Plastics ; Rats ; Spinal Cord Injuries ; Supraoptic Nucleus

Brain natriuretic peptide (BNP) is a neuropeptide, isolated from porcine brain that is homologous with atriopeptin. Magnocellular neurosecretory cells located in the paraventricular nucleus and supraoptic nucleus synthesize and secrete neurohormones. The purpose of this study was to investigate distribution of BNP immunoreactivity throughout the rat hypothalamus from the day of birth to 30 days and adult using immunoperoxidase and immunofluorescent staining. The first BNP immunoreactive neurons appeared in the paraventricular and supraoptic nucleus at P10. In adult, BNP immunoreactivity was widely distributed throughout regions of the hypothalamus including dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus and internal layer of median eminence. The intensity of BNP immunoreactivity was weak in almost all hypothalamic nuclei except the paraventricular and supraoptic nuclei. BNP immunoreactivity was first observed in the lateral hypothalamic area at P15. In retrochiasmatic supraoptic nucleus, BNP immunoreactivity was first observed at P20 and remarkably distributed in adult. In the present study, distinct localization of BNP immunoreactivity was in the hypothalamic cell bodies and fibers. Although the role of BNP in the brain is yet to be determined, these results indicate that BNP in the neurons of hypothalamus play important role in the regulation of a variety of neurosecretory functions as a neuromodulator during postnatal development of the hypothalamus.
Adult ; Animals ; Arcuate Nucleus ; Brain* ; Dorsomedial Hypothalamic Nucleus ; Humans ; Hypothalamic Area, Lateral ; Hypothalamus* ; Immunohistochemistry ; Median Eminence ; Natriuretic Peptide, Brain ; Neurons* ; Neuropeptides ; Neurotransmitter Agents ; Paraventricular Hypothalamic Nucleus ; Parturition ; Rats* ; Supraoptic Nucleus ; Ventromedial Hypothalamic Nucleus

Brain natriuretic peptide (BNP) is a neuropeptide, isolated from porcine brain that is homologous with atriopeptin. Magnocellular neurosecretory cells located in the paraventricular nucleus and supraoptic nucleus synthesize and secrete neurohormones. The purpose of this study was to investigate distribution of BNP immunoreactivity throughout the rat hypothalamus from the day of birth to 30 days and adult using immunoperoxidase and immunofluorescent staining. The first BNP immunoreactive neurons appeared in the paraventricular and supraoptic nucleus at P10. In adult, BNP immunoreactivity was widely distributed throughout regions of the hypothalamus including dorsomedial hypothalamic nucleus, ventromedial hypothalamic nucleus, arcuate nucleus and internal layer of median eminence. The intensity of BNP immunoreactivity was weak in almost all hypothalamic nuclei except the paraventricular and supraoptic nuclei. BNP immunoreactivity was first observed in the lateral hypothalamic area at P15. In retrochiasmatic supraoptic nucleus, BNP immunoreactivity was first observed at P20 and remarkably distributed in adult. In the present study, distinct localization of BNP immunoreactivity was in the hypothalamic cell bodies and fibers. Although the role of BNP in the brain is yet to be determined, these results indicate that BNP in the neurons of hypothalamus play important role in the regulation of a variety of neurosecretory functions as a neuromodulator during postnatal development of the hypothalamus.
Adult ; Animals ; Arcuate Nucleus ; Brain* ; Dorsomedial Hypothalamic Nucleus ; Humans ; Hypothalamic Area, Lateral ; Hypothalamus* ; Immunohistochemistry ; Median Eminence ; Natriuretic Peptide, Brain ; Neurons* ; Neuropeptides ; Neurotransmitter Agents ; Paraventricular Hypothalamic Nucleus ; Parturition ; Rats* ; Supraoptic Nucleus ; Ventromedial Hypothalamic Nucleus

OBJECTIVE: Proopiomelanocortin (POMC) gene is involved in various neuroendocrine reproductive activities and its principal areas of expression are hypothalamus and pituitary gland. However, as it is known as low copy gene, detection of its expression by in situ hybridization is challenging. This study was to examine the degree of basal expression of POMC mRNA and anatomic localization of its expression in rat hypothalamus and pituitary gland as a preliminary study for related reproductive endocrine researches. METHODS: Hypothalamus and pituitary gland of ovariectomized female Spraque-Dawley rat (weight: 250-300 g) was obtained by decapitation with preservation of POMC mRNA by cardiac perfusion of 4% paraformaldehyde. Then, coronal sections of hypothalamus and horizontal sections of pituitary gland were made after paraffin embedding. For in situ hybridization, 35S-labeled antisense RNA probe was used and after in situ hybridization reaction and serial washing procedure, detection of its signal was made by emulsion autoradiography of slide and dark field microscopic examination was done for photographic documentation. Anatomic localization of various nucleus of hypothalamus was done by method proposed by Paxinos and Watson1. RESULTS: Strong expression signal of POMC mRNA was detected in the intermediate lobe of pituitary gland. Less strong, but evenly distributed signals were also detected in the anterior lobe of pituitary gland. In hypothalamic sections, entire area of arcuate nucleus from rostral to caudal direction (between bregma -2.80 mm to bregma -4.30 mm area) showed clear and strong signal of POMC mRNA expression. CONCLUSION: Though POMC gene is known as low copy gene, its basal mRNA expression in pituitary gland and hypothalamus in ovariectomized rat were detectable by in situ hybridization technique. As subpopulation of arcuate nucleus are under complex differential regulation, this in situ hybridization model would be helpful for understanding the effects of various regulatory factors on expression of POMC gene in the specific anatomic area of hypothalamus and pituitary gland.
Animals ; Arcuate Nucleus ; Autoradiography ; Decapitation ; Female ; Humans ; Hypothalamus* ; In Situ Hybridization* ; Paraffin Embedding ; Perfusion ; Pituitary Gland* ; Pituitary Gland, Anterior ; Pituitary Gland, Intermediate ; Pro-Opiomelanocortin* ; Rats* ; RNA, Antisense ; RNA, Messenger