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Galanin-like peptide (GALP) is composed of 60 amino acid residues and its sequence is highly homologous across species. GALP is produced in the hypothalamic arcuate nucleus and has diverse physiological effects such as the regulation of feeding, energy metabolism, and reproductive behavior. GALP-containing neurons express leptin receptors and these neurons form networks in the hypothalamus that contain various peptides that regulate feeding behavior. Recent studies have revealed that GALP has a central anti-obesity action in addition to its role in food intake regulation. Furthermore, we have found that the respiratory quotient declines shortly after administration of GALP into the lateral ventricle. This suggests that lipid metabolism is accelerated by GALP administration, and identifies a new physiological action for this peptide. In this review article, we summarize our recent research focusing on the mechanism whereby GALP regulates feeding and energy metabolism. We concentrate on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system and outline the effectiveness of the nasal administration of GALP and basic research towards its clinical application.

Insulin receptor substrate-1 (Irs1) is one of the major substrates for insulin receptor and insulin-like growth factor-1 (IGF-1) receptor tyrosine kinases. Systemic Irs1-deficient mice show growth retardation, with resistance to insulin and IGF-1, although the underlying mechanisms remain poorly understood. For this study, we generated mice with brain-specific deletion of Irs1 (NIrs1KO mice). The NIrs1KO mice exhibited lower body weights, shorter bodies and bone lengths, and decreased bone density. Moreover, the NIrs1KO mice exhibited increased insulin sensitivity and glucose utilization in the skeletal muscle. Although the ability of the pituitary to secrete growth hormone (GH) remained intact, the amount of hypothalamic growth hormone–releasing hormone (GHRH) was significantly decreased and, accordingly, the pituitary GH mRNA expression levels were impaired in these mice. Plasma GH and IGF-1 levels were also lower in the NIrs1KO mice. The expression levels of GHRH protein in the median eminence, where Irs1 antibody staining is observed, were markedly decreased in the NIrs1KO mice. In vitro, neurite elongation after IGF-1 stimulation was significantly impaired by Irs1 downregulation in the cultured N-38 hypothalamic neurons. In conclusion, brain Irs1 plays important roles in the regulation of neurite outgrowth of GHRH neurons, somatic growth, and glucose homeostasis.

Galanin, galanin-like peptide(GALP), and alarin belong to the galanin family. They are mainly produced in the brain and secreted to the blood, and have indicated various physiological functions. These hormones relate to feeding behavior, although their effects differ between animals. Galanin family hormones are bound to GalRs, including GalR1, GalR2, and GalR3. These receptors are widely distributed in mammal brain, and are involved in rectifying K+ channels (GIRK) and mitogen associated protein (MAPK) signaling pathways. GALP and alarin can bind to these receptors, but several studies have reported that these receptors are not specific.

Objective Previous human and animal studies have shown that excessive maternal intake of folic acid (FA) predisposes to impaired glucose tolerance in the offspring. However, the underlying mechanism is unknown. Therefore, we aimed to determine whether excessive supplementation with FA during pregnancy affects the glucose tolerance of mouse offspring. Research methods & procedures Pregnant C57BL/6J mice were fed AIN93G diet containing either 2 mg [control group (CN)] or 40 mg [high FA group (HFA)] FA/kg diet throughout their pregnancies. On postnatal days (PD)22 and 50, fasting blood glucose was measured in the offspring of both groups, and an oral glucose tolerance test (OGTT) was performed on PD50. On PD53, tissues were collected, and the tissue masses, area of insulin expression in the pancreas, liver triglyceride content, and gene expression were determined. Results The blood glucose concentrations at 60 and 120 min of the OGTT were higher in female HFA than CN offspring. The serum fasting and non-fasting insulin concentrations and the area of insulin expression in the pancreas were lower in HFA than CN offspring. The liver triglyceride content was higher in female, and tended to be higher in male (P < 0.05), HFA offspring than CN offspring (P < 0.05). The liver mRNA expression of fat synthesis genes, such as Pparγ2 (male and female) and Cidec (male), was higher in HFA than CN offspring (P < 0.05). Conclusion Excessive maternal supplementation of FA in mice leads to lower insulin synthesis and an impairment in hepatic fat metabolism in the offspring., Biochemistry; Nutrition; Health Sciences; Pregnancy; Metabolism; Metabolic Disorder; folic acid; insulin; impaired glucose tolerance; fat metabolism

Previous studies have shown that dissolved substances in some natural hot springs have analgesic/anti-nociceptive and anti-inflammatory actions. However, the mechanisms underlying how such dissolved substances exert these actions are not fully understood. In the present study on mice, we examined the analgesic/anti-nociceptive and anti-inflammatory properties of a mineral cream containing natural hot spring ingredients. The anti-nociceptive effects of the mineral cream were assessed by using the von Frey test. Application of the mineral cream to the hind paw of mice produced a significant anti-nociceptive effect compared to control. The anti-nociceptive effects of the mineral cream were also assessed following the injection of complete Freund's adjuvant (CFA) into the hind paws of mice after pre-treatment for one or four weeks with the mineral cream. Histological experiments with light microscopy showed that the mineral cream did not reduce inflammation caused by the CFA treatment. In addition, the mineral cream did not inhibit oxidative stress as evidenced by increased levels of oxidative metabolites (d-ROMs) and biological anti-oxidant potential (BAP). These results suggest that the mineral cream does not exert a protective effect against inflammation, and that the constituents of the mineral cream may produce their anti-nociceptive effects transdermally via different mechanisms including the nervous system.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide/glucagon/secretin family of peptides. PACAP and its three receptor subtypes are expressed in neural tissues and in the eye, including the retina, cornea, and lacrimal gland. PACAP is known to exert pleiotropic effects on the central nervous system and in eye tissues where it plays important roles in protecting against dry eye. This review provides an overview of current knowledge regarding dry eye symptoms in aged animals and humans and the protective effects, mechanisms of action. In addition, we also refer to the development of a new preventive/therapeutic method by PACAP of dry eye patients.

The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine-N-oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues.

This study investigates effects of dipeptide balenine, as a major component of whale meat extract (hereafter, WME), supplementation on senescence-accelerated mouse prone 8 (SAMP8), an Alzheimer's disease (AD) model at level of learning and memory formation and brain expression profiles genome-wide in brain. Mice fed experimental balenine (+ WME) supplemented diet for 26 weeks were subjected to four behavioral tests – open field, Y-maze, novel object recognition, and water-filled multiple T-maze – to examine effects on learning and memory. Brain transcriptome of SAMP8 mice-fed the WME diet over control low-safflower oil (LSO) diet-fed mice was delineated on a 4 × 44 K mouse whole genome DNA microarray chip. Results revealed the WME diet not only induced improvements in the learning and memory formation but also positively modulated changes in the brain of the SAMP8 mouse; the gene inventories are publically available for analysis by the scientific community. Interestingly, the SAMP8 mouse model presented many genetic characteristics of AD, and numerous novel molecules ( Slc2a5 , Treh , Fbp1 , Aldob , Ppp1r1a , DNase1 , Agxt2l1 , Cyp2e1 , Acsm1 , Acsm2 , and Pah ) were revealed over the SAMR1 (senescence-accelerated mouse resistant 1) mouse, to be oppositely regulated/recovered under the balenine (+ WME) supplemented diet regime by DNA microarray and bioinformatics analyses. Our present study demonstrates an experimental strategy to understand the effects of dipeptide balenine, prominetly contained in meat diet, on SAMP8, providing new insight into whole brain transcriptome changes genome-wide. The gene expression data has been deposited into the Gene Expression Omnibus (GEO): GSE76459 . The data will be a valuable resource in examining the effects of natural products, and which could also serve as a human model for further functional analysis and investigation.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues of the eye, including the retina, cornea and lacrimal gland, and PACAP is known to exert pleiotropic effects throughout the central nervous system. This review provides an overview of current knowledge regarding the cell protective effects, mechanisms of action and therapeutic potential of PACAP in response to several types of eye injury.

Whale oil (WO) contains n-3 polyunsaturated fatty acids (PUFAs), but the effects of whale oil intake on lipid metabolism have remained unclear. We examined the influence of WO on lipid metabolism in obese KK mice. Male KK mice were fed a high-fat diet for 12 weeks to induce obesity. The mice were then given free access to a different diet for 10 weeks: the lard/safflower oil (LSO) diet consisted of 25 energy% (en%) LSO (6:4), the WO diet consisted of 25 en% WO, and the fish oil (FO) diet consisted of 11 en% FO plus 14 en% LSO. The n-3 PUFA content of the FO diet was the same as that in the WO diet. In the WO and FO groups, the total plasma cholesterol level was significantly decreased compared with that in the LSO group. The number of lipid droplets in liver specimens was also lower in the WO and FO groups, and the hepatic triglyceride and total cholesterol levels were decreased in these groups compared with the LSO group. Hepatic mRNA levels of fatty acid synthase, and stearoyl-CoA desaturase 1, which are fatty acid synthesis-related genes, were decreased in the WO and FO groups. No significant differences were observed between the WO and FO groups. Taken together, these results indicate that WO intake inhibits lipid accumulation in the liver by reducing fatty acid biosynthesis.

Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid receptor (GR) has been reported to regulate the clock genes, but the underlying mechanisms are incompletely understood. In this study, we focused on the suppressive effect of the GR on the expression of Rev-erbα (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erbα expression via the formation of a complex with CLOCK and BMAL1, which binds to the E-boxes in the Nr1d1 promoter. In this GR-CLOCK-BMAL1 complex, the GR does not directly bind to DNA, which is referred to as tethering. These findings provide new insights into the role of the GR in the control of circadian rhythm.

Previous studies have shown that dissolved substances in some natural hot springs have analgesic/anti-nociceptive and anti-inflammatory actions. However, the mechanisms underlying how such dissolved substances exert these actions are not fully understood. In the present study on mice, we examined the analgesic/anti-nociceptive and anti-inflammatory properties of a mineral cream containing natural hot spring ingredients. The anti-nociceptive effects of the mineral cream were assessed by using the von Frey test. Application of the mineral cream to the hind paw of mice produced a significant anti-nociceptive effect compared to control. The anti-nociceptive effects of the mineral cream were also assessed following the injection of complete Freund's adjuvant (CFA) into the hind paws of mice after pre-treatment for one or four weeks with the mineral cream. Histological experiments with light microscopy showed that the mineral cream did not reduce inflammation caused by the CFA treatment. In addition, the mineral cream did not inhibit oxidative stress as evidenced by increased levels of oxidative metabolites (d-ROMs) and biological anti-oxidant potential (BAP). These results suggest that the mineral cream does not exert a protective effect against inflammation, and that the constituents of the mineral cream may produce their anti-nociceptive effects transdermally via different mechanisms including the nervous system.

Background: Selective sodium-glucose cotransporter 2 inhibitor (SGLT2i) has become widely used for treatment of diabetes. Recently, EMPA-REG OUTCOME and CANVAS Program showed that SGLT2i reduce cardiovascular events in patients with type 2 diabetes, but the mechanism still remains uncertain. We investigated the mechanisms of vascular protection of Tofogliflozin (Tofo), one of the SGLT2i. Method: 1) Streptozotocin (STZ)-diabetic apolipoprotein-E-deficient (ApoE KO) mice were separated into two groups, one group were fed normal chow and the other were fed normal chow containing 0.005% Tofo for ad libitum. After 6weeks, all mice were administered thioglycolate intraperitoneally, and 4 days later, peritoneal macrophages were collected to investigate the expressions of inflammatory cytokines of peritoneal macrophages by real-time PCR. Histological analyses were carried out by Sudan IV, Oil Red O, and MOMA-2 staining. 2) The same experiment targeted were carried out towards nondiabetic ApoE KO mice. Results: 1) Tofo increased food and water intake and decreased blood glucose, but there were no significant changes in body weight, serum levels of free fatty acid, triglyceride and total cholesterol between two groups. The legions of atherosclerosis and macrophages accumulations were significantly suppressed in Tofo group. Moreover, the expression levels of TNF-α, IL-β were significantly suppressed in macrophages from Tofo group. 2) Nondiabetic ApoE KO mice showed similar increase in food and water intake, but failed to exhibit differences in blood glucose, Sudan IV staining, and expressions of inflammatory cytokines in macrophages, as observed in diabetic ApoE KO mice. Conclusion: Tofogliflozin suppresses the progression of atherosclerosis and reduces inflammation in macrophages of STZ- diabetic ApoE KO mice. These beneficial effects may be exerted due to improvement of glucose tolerance. Disclosure M. Iwamoto: None. N. Kubota: None. T. Kubota: None. Y. Sakurai: None. N. Wada: None. I. Takamoto: None. S. Shioda: None. T. Kadowaki: Consultant; Self; Novo Nordisk A/S, AstraZeneca, Merck Sharp & Dohme Corp.. Research Support; Self; Kissei Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Sanofi, Kyowa Hakko Kirin Co., Ltd., Novo Nordisk A/S, Astellas Pharma, Daiichi Sankyo Company, Limited, Takeda, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Merck Sharp & Dohme Corp., Nippon Boehringer Ingelheim Co. Ltd.. Speaker's Bureau; Self; Astellas Pharma, AstraZeneca, Merck Sharp & Dohme Corp., Ono Pharmaceutical Co., Ltd., Takeda, Eli Lilly and Company, Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk A/S.

Although considerable progress has been made in understanding how the temporal and regional control of neural progenitor cells (NPCs) dictates their fate, their key regulators during neural development are still unknown. Ghrelin, which is isolated from porcine stomach extract, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The widespread expression of ghrelin and GHS-R in the central nervous system during development suggests that ghrelin may be involved in developmental neural growth. However, its role in regulating fetal NPCs is still unclear. In this study, we investigated the effects of ghrelin on primary cultured NPCs derived from fetal mouse telencephalon. The expressions of both ghrelin and its receptor were observed in NPCs using RT-PCR, immunoblotting and immunocytostaining. Interestingly, the exposure of fetal NPCs to ghrelin at concentrations of 10(-7) and 10(-9)M suppressed their proliferation, and caused them to differentiate into neurons and to extend neurites. These results strongly suggest that ghrelin plays an autocrine modulatory role in fetal neural development.

Neuropeptide W (NPW), which was originally isolated from the porcine hypothalamus, has been identified as the endogenous ligand for both the NPBWR1 (GPR7) and NPBWR2 (GPR8) receptors. These receptors, which belong to the orphan G protein-coupled receptor (GPCR) family, share a high sequence homology with the opioid and somatostatin receptor families. NPW and NPBWR1 are widely distributed in the rat central nervous system (CNS). While the intracerebroventricular (i.c.v.) injection of NPW elevates plasma corticosterone levels, the intravenous administration of NPW in conjunction with a corticotropin-releasing hormone (CRH) antagonist blocks NPW-induced corticosterone secretion. It has been reported that NPW is involved in regulating the hypothalamus-pituitary-adrenal cortex (HPA) axis and that i.c.v. administration of NPW decreases feeding behavior. The aim of the present study was to ascertain if NPW's role in feeding regulation is mediated (or not) through corticotropin-releasing hormone (CRH)-containing neurons. We found that NPW-containing axon terminals make synapses with CRH-immunoreactive cell bodies and dendritic processes in the hypothalamic paraventricular nucleus (PVN). The central infusion of NPW significantly induced c-Fos expression in CRH-immunoreactive neurons in the mouse PVN, but not in vasopressin- or oxytocin-immunoreactive neurons. To determine if NPW regulates feeding behavior through CRH neurons, the feeding behavior of mice was studied following the i.c.v. administration NPW in the presence or absence of pretreatment with a CRH antagonist. While NPW administration decreased feeding activity, the CRH antagonist inhibited this effect. These results strongly suggest that NPW regulates feeding behavior through CRH neurons in the mouse brain.

Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of food intake behavior, body weight and energy metabolism. In previous studies, we demonstrated that the intranasal administration of GALP has weight loss effects, although the mechanism of this action was not clarified. The aim of this study was to demonstrate the functional significance of GALP on lipid metabolism in the liver. Mice were fed a high fat diet to cause diet-induced obesity (DIO) and then administered GALP intranasally for 2 weeks (experimental), or vehicle (control). Body weights, along with lipid levels in the plasma and liver, and lipid metabolism-related gene expression in the liver were subsequently measured. Body weight gain was decreased by the GALP treatment compared to the control group. Lipid droplet levels in hepatocytes and hepatic triglyceride levels were decreased in the GALP group compared with the vehicle group, whereas hepatic fatty acid β-oxidation-related gene mRNA levels were increased in the GALP group. These results suggest that the intranasal administration of GALP has an inhibitory effect on lipid accumulation in the liver.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have both anti-diabetic and anti-obesity effects. However, the precise mechanism of the anti-obesity effect remains unclear. We previously demonstrated that the glycogen depletion signal triggers lipolysis in adipose tissue via liver-brain-adipose neurocircuitry. In this study, therefore, we investigated whether the anti-obesity mechanism of SGLT2 inhibitor is mediated by this mechanism. Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks. TOFO-treated mice showed a decrease in fat mass and the effect of TOFO was attenuated in HVx group. Although both HVx and sham mice showed a similar level of reduction in hepatic glycogen by TOFO treatment, HVx mice exhibited an attenuated response in protein phosphorylation by protein kinase A (PKA) in white adipose tissue compared with the sham group. As PKA pathway is known to act as an effector of the liver-brain-adipose axis and activate triglyceride lipases in adipocytes, these results indicated that SGLT2 inhibition triggered glycogen depletion signal and actuated liver-brain-adipose axis, resulting in PKA activation in adipocytes. Taken together, it was concluded that the effect of SGLT2 inhibition on weight loss is in part mediated via the liver-brain-adipose neurocircuitry.

Leptin is mainly produced in the white adipose tissue before being secreted into the blood and transported across the blood-brain barrier. Leptin binds to a specific receptor (LepR) that has numerous subtypes (LepRa, LepRb, LepRc, LepRd, LepRe, and LepRf). LepRb, in particular, is expressed in several brain nuclei, including the arcuate nucleus, the paraventricular nucleus, and the dorsomedial, lateral and ventromedial regions of the hypothalamus. LepRb is also co-expressed with several neuropeptides, including proopiomelanocortin, neuropeptide Y, galanin, galanin-like peptide, gonadotropin-releasing hormone, tyrosine hydroxylase and neuropeptide W. Functionally, LepRb induces activation of the JAK2/ERK, /STAT3, /STAT5 and IRS/PI3 kinase signaling cascades, which are important for the regulation of energy homeostasis and appetite in mammals. In this review, we discuss the structure, genetics and distribution of the leptin receptors, and their role in cell signaling mechanisms.

Neuropeptide Y (NPY) is a 36-amino-acid neuropeptide that was first discovered in porcine brain extracts and later in the porcine intestine. It is widely distributed in both the central and peripheral nervous systems and exerts a powerful orexigenic effect. NPY-producing neuronal cell bodies are abundantly localized in the medial arcuate nucleus of the hypothalamus, this being a brain center that integrates signals for energy homeostasis. Accumulated evidence shows that hypothalamic neuropeptides such as ghrelin, orexin, melanin-concentrating hormone (MCH), galanin-like peptide (GALP) and proopiomelanocortin (POMC) are involved in the regulation of feeding behavior and energy homeostasis via neuronal circuits in the hypothalamus. NPY also forms part of the feeding-regulating neuronal circuitry in conjunction with other feeding-regulating peptide-containing neurons within the hypothalamus. We summarize here current knowledge of the neuronal interactions between NPY and the different types of feeding-regulating peptide-containing neurons in the hypothalamus based on evidence at the immunohistochemicl level and with calcium imaging techniques.

Galanin-like peptide (GALP) is a neuropeptide involved in the regulation of feeding behavior and energy metabolism in mammals. While a weight loss effect of GALP has been reported, its effects on lipid metabolism have not been investigated. The aim of this study was to determine if GALP regulates lipid metabolism in liver and adipose tissue via an action on the sympathetic nervous system. The respiratory exchange ratio of mice administered GALP intracerebroventricularly was lower than that of saline-treated animals and fatty acid oxidation-related gene mRNA levels were increased in the liver. Even though the respiratory exchange ratio was reduced by GALP, this change was not significant when mice were treated with the sympatholytic drug, guanethidine. Lipolysis-related gene mRNA levels were increased in the adipose tissue of GALP-treated mice compared with saline-treated animals. These results show that GALP stimulates fatty acid β-oxidation in liver and lipolysis in adipose tissue and suggest that the anti-obesity effect of GALP may be due to anorexigenic actions and improvement of lipid metabolism in peripheral tissues via the sympathetic nervous system.

Alarin is a recently discovered member of the galanin peptide family encoded by a splice variant of galanin-like peptide (GALP) mRNA. Alarin mRNA has been detected in the mouse brain, skin, and thymus, and alarin-like immunoreactivity (alarin-LI) has been observed in different areas of the murine brain. Alarin also participates in the regulation of feeding, metabolism, and reproduction, where it stimulates feeding behavior, increases body weight, and influences luteinizing hormone and gonadotropin-releasing hormone secretion.

Leptin is an adipose-derived hormone and consists of 146 aa residues. Leptin is involved in several functions such as feeding, thermogenesis, fertilization, and hormonal secretion. Leptin binds to leptin receptors and activates intracellular signaling pathways such as JAK-STAT, PI3/Akt, and MAPK. Rodents which have been reported with leptin gene mutation (e.g., db/db mouse, fak/ fak rat) have morbid obesity, hyperglycemia, hyperleptinemia, and hypothalamic hypogonadism. Human leptin analog is used for treatment of dystrophy.

Aquaporin (AQP) 7 and AQP9 are subcategorised as aquaglyceroporins which transport glycerin in addition to water. These AQPs may play a role in the homeostasis of energy metabolism. We examined the effect of AQP7, AQP9, and lipid metabolism-related gene expression in obese mice. In diet-induced obese (DIO) mice, excess lipid accumulated in the liver, which was hyperleptinemic and hyperinsulinemic. Hepatic AQP9 gene expression was significantly increased in both DIO and ob/ob mice compared to controls. The mRNA expression levels of fatty acid and triglyceride synthesis-related genes and fatty acid β oxidation-related genes in the liver were also higher in both mouse models, suggesting that triglyceride synthesis in this organ is promoted as a result of glycerol release from adipocytes. Adipose AQP7 and AQP9 gene expressions were increased in DIO mice, but there was no difference in ob/ob mice compared to wild-type mice. In summary, adipose AQP7 and AQP9 gene expressions are increased by diet-induced obesity, indicating that this is one of the mechanisms by which lipid accumulates in response to a high fat diet, not the genetic mutation of ob/ob mice. Hepatic AQP9 gene expression was increased in both obesity model mice. AQP7 and AQP9 therefore have the potential of defining molecules for the characterisation of obesity or fatty liver and may be a target molecules for the treatment of those disease.

Galanin-like peptide (GALP) is a 60 amino acid neuropeptide that was first isolated from the porcine hypothalamus. It is produced in the hypothalamic arcuate nucleus by neurons that form networks with other neurons containing peptides involved in the control of feeding behavior. GALP plays an important role in the regulation of feeding, body weight and energy metabolism. Although the physiological actions of GALP are yet to be fully elucidated, it is possible, given the anti-obesity effect of GALP seen in relation to food intake and body weight loss in obese mice, that GALP could be applied clinically to combat obesity in humans. Here we summarize what is known about the regulation of energy metabolism by GALP, and describe results in animals that could possibly lead to the clinical use of GALP to treat obesity.

胃潰瘍に対する胃機能保存手術としての迷走神経切断術 (迷切) の意義を検討するため, 実験的ならびに臨床的研究を行った.その結果, 高酸下の潰瘍ではSelective proximal vagotomy (SPV) などの迷切は犬に作成した酢酸潰瘍の治癒に好影響を与えたが, 幽門形成術または幽門洞切除合併手術はかえって胆汁逆流による影響が推測され, SPV単独手術よりも不良であった.一方, 非高酸下の潰瘍では迷切はむしろ潰瘍治癒に不良な影響を示した.臨床例における胃切除兼Selective vagotomy (SV) の減酸率は約90%と大きく, 胃機能検査でもSV非合併手術に比べ不良なものはなかった.今後適応を決め, 迷切を併用すれば, 胃切除量を少くでき, 胃機能保存手術も可能と思われる.