galanin-like-peptide and Obesity

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.

Topics: Animals; Anti-Obesity Agents; Energy Metabolism; Feeding Behavior; Galanin-Like Peptide; Humans; Obesity

Scientific and commercial pharmacological interest in the role of galanin and galanin receptors in the regulation of food intake, energy balance, and obesity has waned recently, following initial enthusiasm during the 1980-1990s. It has been replaced by efforts to understand the role of newly discovered peptide systems such as the hypocretin/orexins, melanocortins and cocaine- and amphetamine-regulated transcript (CART) and their relationship to the important hormones, leptin and insulin. Thus, while numerous studies have revealed the ability of galanin to stimulate food intake via actions at sites within the hypothalamus, and shown reliable changes in hypothalamic galanin synthesis in response to food ingestion; findings including the lack of a 'body weight/obesity' phenotype in galanin transgenic mouse strains and a lack of agonists/antagonists for galanin receptor subtypes have probably served to reduce enthusiasm. However, as more is learnt about the general and galanin-related neurochemistry of brain pathways involved in feeding, metabolism and body weight control, the potential importance of galanin systems is again in focus. Studies of the newly discovered galanin family peptide, 'galanin-like peptide' (GALP), highlight the likely role of galanin peptides and receptors in the physiological coupling of body weight, adiposity and reproductive function. GALP is produced by a discrete population of neurons within the basomedial arcuate nucleus (and median eminence) that send projections to the anterior paraventricular nucleus and that make close contacts with leutinizing hormone-releasing hormone (LHRH) neurons in basal forebrain. Furthermore, GALP neurons express leptin receptors and respond to leptin treatment by increasing their expression of GALP mRNA. Centrally administered GALP activates LHRH-immunoreactive neurons and increases plasma LH levels. These findings suggest a direct stimulatory action of endogenous GALP on gonadotropin secretion via actions within the hypothalamus/basal forebrain, with leptin actions linking this system to body adipose levels.

Topics: Amino Acid Sequence; Body Weight; Eating; Galanin; Galanin-Like Peptide; Gene Expression; Humans; Hypothalamus; Models, Biological; Molecular Sequence Data; Mutation; Nerve Tissue Proteins; Neurons; Obesity; Receptors, Galanin; Receptors, Neuropeptide; Sequence Homology, Amino Acid

We aimed to investigate serum galanin-like peptide (GALP) levels and their correlation with hormonal and metabolic parameters in patients with polycystic ovary syndrome (PCOS).. The study included 48 women (age range, 18-44 years) with a diagnosis of PCOS, and a control group that included 40 healthy females (age range, 18-46 years). Waist circumference, body mass index (BMI), and Ferriman-Gallwey score were evaluated and plasma glucose, lipid profile, oestradiol, progesterone, total testosterone, prolactin, insulin, dehydroepiandrosterone sulphate (DHEA-S), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), 25-hydroxyvitamin D (25(OH)D), fibrinogen, d-dimer, C-reactive protein (CRP), and GALP levels were measured in all study subjects.. Waist circumference (p = 0.044) and Ferriman-Gallwey score (p = 0.002) were significantly higher in patients with PCOS compared to the control group. Among the metabolic and hormonal parameters studied, only total testosterone was significantly higher in patients with PCOS (p = 0.002). Also, the serum 25(OH)D level was significantly lower in the PCOS group (p = 0.001). CRP, fibrinogen, and D-dimer levels were all similar between the 2 groups. Serum GALP level was significantly higher in PCOS patients (p = 0.001). GALP was negatively correlated with 25(OH)D (r = -0.401, p = 0.002) and positively correlated with total testosterone values (r = 0.265, p = 0.024). Multiple regression analysis revealed that both total testosterone and 25(OH)D significantly contributed to GALP levels.. Our study is the first in the literature to evaluate serum GALP levels in patients with PCOS. Increased GALP levels in PCOS and its association with total testosterone levels might show that GALP can act as an intermediary in increased GnRH-mediated LH release, which is one of the underlying pathogenetic mechanism of PCOS.

Topics: Adolescent; Adult; Androgens; Body Mass Index; C-Reactive Protein; Female; Fibrinogen; Follicle Stimulating Hormone; Galanin-Like Peptide; Humans; Insulin; Luteinizing Hormone; Middle Aged; Obesity; Polycystic Ovary Syndrome; Testosterone; Young Adult

The aim of this research was to test the efficacy and potential clinical application of intranasal administration of galanin-like peptide (GALP) as an anti-obesity treatment under the hypothesis that GALP prevents obesity in mice fed a high-fat diet (HFD). Focusing on the mechanism of regulation of lipid metabolism in peripheral tissues via the autonomic nervous system, we confirmed that, compared with a control (saline), intranasally administered GALP prevented further body weight gain in diet-induced obesity (DIO) mice with continued access to an HFD. Using an omics-based approach, we identified several genes and metabolites in the liver tissue of DIO mice that were altered by the administration of intranasal GALP. We used whole-genome DNA microarray and metabolomics analyses to determine the anti-obesity effects of intranasal GALP in DIO mice fed an HFD. Transcriptomic profiling revealed the upregulation of flavin-containing dimethylaniline monooxygenase 3 (

Topics: Administration, Intranasal; Animals; Diet, High-Fat; Fatty Acids; Galanin-Like Peptide; Lipid Metabolism; Liver; Metabolome; Mice; Mice, Inbred C57BL; Obesity; Oligonucleotide Array Sequence Analysis; Transcriptome; Weight Gain

To study the level of circulating Alarin in obese children and its association with various metabolic parameters.. A total of 86 obese children with a body mass index (BMI) above the 95th percentile were enrolled as the obesity group, and 82 healthy children, matched for age and sex, with a BMI below the 85th percentile were enrolled as the healthy control group. According to the presence or absence of insulin resistance (IR), the obesity group was further divided into an IR group with 27 children and a non-IR group with 59 children. Related anthropometric parameters, including body height, body weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP), were measured, and BMI was calculated. Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), uric acid (UA), fasting insulin (FINS), and fasting blood glucose (FBG) were measured. The area under the receiver operating characteristic curve (AUC) for glucose and insulin, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and whole-body insulin sensitivity index (WBISI) were calculated. ELISA was used to measure the level of circulating Alarin.. The obesity group had a significantly higher level of circulating Alarin than the healthy control group (P<0.01). The IR group had a significantly higher level of circulating Alarin than the non-IR group (P<0.01). Circulating Alarin was positively correlated with BMI, TG, FBG, AUC-glucose, AUC-FINS, and HOMA-IR (P<0.05) and was negatively correlated with WBISI (P<0.05). The circulating Alarin level had a linear regression relationship with BMI, FBG, and HOMA-IR, among which HOMA-IR had the greatest influence on the circulating Alarin level (P<0.05).. There is a significant increase in the circulating Alarin level in obese children, which may be associated with the development of obesity and IR.

Topics: Blood Glucose; Body Mass Index; Child; Galanin-Like Peptide; Humans; Insulin; Insulin Resistance; Obesity

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.

Topics: Administration, Intranasal; Animals; Body Weight; Diet, High-Fat; Galanin-Like Peptide; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Obesity; Treatment Outcome

Galanin-like peptide (GALP) has an anti-obesity effect in rats and mice. It has been reported that the uptake of GALP by the brain is higher after intranasal administration than with intravenous injection. This study therefore aimed to clarify the effect of intranasal administration of GALP on the feeding behavior of lean and obese mice. Autoradiography revealed the presence of (125)I-GALP in the olfactory bulb and the brain microcirculation. The body weights of ob/ob mice gradually increased during vehicle treatment, but remained unchanged in response to repeated intranasal administration of GALP, with both ob/ob and diet-induced obese mice displaying significantly decreased food intake, water intake and locomotor activity when treated with GALP. These results suggest that intranasal administration is an effective route whereby GALP can exert its effect as an anti-obesity drug.

Topics: Administration, Intranasal; Animals; Anti-Obesity Agents; Autoradiography; Body Weight; Brain; Energy Metabolism; Galanin-Like Peptide; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Rats; Rats, Sprague-Dawley

Obesity is strongly linked to metabolic complications, including type 2 diabetes mellitus and hyperlipidemia. Experimental evidences indicate that galanin (GAL) and galanin-like peptide (GALP) are involved in the regulation of feeding behavior and energy metabolism. We evaluated the possible relationships between both peptide concentrations and blood fat indexes in obese and normal subjects.. The study groups consisted of 41 obese subjects (age 35.17±12.29year, BMI 30.97±2.75kg/m(2)) and 38 healthy controls (age 38.47±11.63year, BMI 22.83±3.00kg/m(2)). Plasma GAL and GALP concentration was determined using ELISA.. Plasma GAL and GALP concentration was significantly higher in obese subjects than healthy controls (P<0.001). In addition, the positive correlations were found between: GAL and triglyceride (TG) concentrations (r=0.636; P<0.001), GALP and TG concentrations (r=0.362; P=0.020) in obese subjects.. Our results indicated that obese individuals have higher plasma GAL and GALP concentrations and both peptide concentrations were positively correlative to TG concentrations in obese human. GAL and GALP concentrations may be taken as potential biomarkers to predict development of obesity.

Topics: Adult; Female; Galanin; Galanin-Like Peptide; Humans; Male; Obesity; Triglycerides

It has been suggested that nutritional manipulations during the first weeks of life can alter the development of the hypothalamic circuits involved in energy homeostasis. We studied the expression of a large number of the hypothalamic neuropeptide mRNAs that control body weight in mice that were overfed during breastfeeding (mice grown in a small litter, SL) and/or during adolescence (adolescent mice fed a high-fat diet, AHF). We also investigated possible alterations in mRNA levels after 50 days of a high-fat diet (high-fat challenge, CHF) at 19 weeks of age. Both SL and AHF conditions caused overweight during the period of developmental overfeeding. During adulthood, all of the mouse groups fed a CHF significantly gained weight in comparison with mice fed a low-fat diet, but the mice that had undergone both breast and adolescent overfeeding (SL-AHF-CHF mice) gained significantly more weight than the control CHF mice. Of the ten neuropeptide mRNAs studied, only neuropeptide Y (NPY) expression was decreased in all of the groups of developmentally overfed adult mice, but CHF during adulthood by itself induced a decrease in NPY, agouti-related protein (AgRP) and orexin (Orx) mRNA levels. Moreover, in the developmentally overfed CHF mice NPY, AgRP, galanin (GAL) and galanin-like peptide (GalP) mRNA levels significantly decreased in comparison with the control CHF mice. These results show that, during adulthood, hypothalamic neuropeptide systems are altered (NPY) and/or abnormally respond to a high-fat diet (NPY, AgRP, GAL and GalP) in mice overfed during critical developmental periods.

Topics: Agouti-Related Protein; Animals; Animals, Newborn; Body Weight; Diet, Fat-Restricted; Diet, Ketogenic; Dietary Fats; Female; Galanin; Galanin-Like Peptide; Gene Expression; Gene Expression Regulation, Developmental; Hypothalamus; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neuropeptide Y; Neuropeptides; Obesity; Orexins; Overnutrition; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Animals; Eating; Feeding Behavior; Galanin-Like Peptide; Humans; Obesity

Galanin-like peptide (GALP), a ligand for three types of galanin receptor, is reported to have a role in regulating luteinising hormone (LH) release in male rodents and primates, but its role in LH release in female rodents remains controversial. The present study was conducted to test whether GALP has a stimulatory role in regulating LH secretion in female rats. The effect of i.c.v. infusion of GALP (5 nmol) on pulsatile LH release was investigated in Wistar-Imamichi strain female rats, or lean and obese Zucker rats. In oestradiol-17beta (oestradiol)-primed ovariectomised (OVX) Wistar-Imamichi female rats, i.c.v. infusion of GALP caused a gradual increase in LH release for the first 1.5 h after the infusion followed by an increased LH pulse frequency during the next 1.5 h, resulting in a significant increase in the mean LH concentrations and baseline levels of LH pulses throughout the sampling period and in the frequency of LH pulses at the last half of the period compared to vehicle-treated controls. The stimulatory effect of GALP was oestrogen-dependent because the same GALP treatment did not affect LH release in OVX rats in the absence of oestradiol. In lean Zucker rats, LH pulses were found in oestradiol-primed OVX individuals and central GALP infusion increased mean LH concentrations in the last half of the period. By contrast, few LH pulses were found in oestradiol-primed OVX obese Zucker rats reportedly with lower hypothalamic GALP expression. Central GALP infusion caused an apparent but transient increase in LH release, resulting in the significant increase in all pulse parameters of LH pulses compared to vehicle-treated controls in the first half of the sampling period. These results suggest that hypothalamic GALP is likely involved in stimulating GnRH/LH release, and that the stimulatory effect of GALP on LH release is oestrogen-dependent in female rats.

Topics: Animals; Estradiol; Female; Galanin-Like Peptide; Luteinizing Hormone; Obesity; Ovariectomy; Pulsatile Flow; Rats; Rats, Wistar; Rats, Zucker; Thinness

Galanin-like peptide (GALP) is a newly identified neuropeptide implicated in the regulation of metabolism and reproduction. GALP gene expression is decreased in the hypothalamus of genetically obese rodents, such as fa/fa rats and ob/ob mice, and central administration of GALP increases feeding in satiated rats. The effect of dietary obesity on GALP-induced feeding is unknown, so this study characterized the effects of central administration of GALP on feeding in a rat model of diet-induced obesity. Male Sprague-Dawley rats (n = 21) were randomly assigned to receive standard laboratory chow (12% fat as kcal) or high-fat cafeteria diet (35% fat) for 12 weeks before intracerebroventricular (icv) cannulae were implanted. Seven days later, rats received 0,0.2 or 0.3 nmol doses of GALP in randomized order at least 48 h apart. Food intake was measured at 0.5,1,2, 4 and 24 h post administration and body weight was measured at 24 h. Rats were maintained on their respective diets throughout the entire feeding experiment. Implementation of the high-fat diet led to significantly greater caloric intake (230%) and body weight (28%) compared to chow-fed control rats. GALP-induced feeding was rapid and maximal in both dietary groups at 30 min post injection. The 0.3 nmol dose of GALP led to significantly larger increases in caloric intake in high-fat fed rats than in chow-fed controls (35.4 +/- 3.7 and 22.1 +/- 1.3 kcal, respectively, at 30 min). It is not known if diet-induced obesity alters endogenous GALP levels, but our data suggest that adaptive responses in GALP signaling might occur during chronic overfeeding. One possible explanation is an increased sensitivity and/or number of specific GALP receptors, although actions of exogenous GALP may also represent pharmacological actions at galanin receptors.

Topics: Animal Feed; Animals; Dietary Fats; Feeding Behavior; Galanin-Like Peptide; Hypothalamus; Male; Microinjections; Obesity; Rats; Rats, Sprague-Dawley; Satiation

We examined the galanin-like peptide (GALP) gene expression in the arcuate nucleus (ARC) and posterior pituitary (PP) in 6- and 18-week-old male obese fa/fa rats. GALP mRNA in the ARC in fa/fa rats was significantly decreased in 6- and 18-week-old and GALP mRNA in the PP in fa/fa rats was significantly increased in 18-week-old compared to lean Fa/? rats. Insulin treatment in hyperglycemic fa/fa rats partially reversed those changes. These results suggest that the GALP gene expression in fa/fa rats might be regulated in part by leptin-independent mechanisms.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Blood Glucose; Galanin-Like Peptide; Gene Expression Regulation; Hyperglycemia; Insulin; Leptin; Male; Neuropeptide Y; Obesity; Pituitary Gland, Posterior; Pro-Opiomelanocortin; Rats; Rats, Mutant Strains; RNA, Messenger

Galanin-like peptide (GALP) is a 60-amino-acid peptide with structural similarities to galanin and a high affinity for galanin receptors. GALP is expressed by a discrete population of neurons in the arcuate nucleus (ARC) and median eminence of the hypothalamus of several species, including the rat. GALP neurons express leptin receptors and GALP mRNA levels are decreased slightly in fasted rats and stimulated significantly by acute leptin treatment in combination with fasting. In studies to further explore the leptin dependence of GALP expression, we examined GALP mRNA levels in the hypothalamus of obese Zucker and streptozotocin-induced diabetic (STZ-DM) rats. In leptin receptor-deficient obese Zucker rats, with 75% higher body weight than lean littermates, GALP mRNA levels in the ARC were decreased by 75%, while neuropeptide Y (NPY) mRNA levels were increased 7-fold (n = 5, p < 0.001), consistent with earlier reports. In hypoleptinemic diabetic rats with 4.5-fold higher blood glucose and 15% lower body weight than controls, GALP mRNA levels in the ARC were decreased by 90%, while NPY mRNA levels were increased 9-fold (n = 5, p < 0.001). GALP is also expressed by pituicytes in the neural lobe of the rat pituitary gland and GALP expression is increased by osmotic stimulation such as dehydration and salt loading. Thus, in STZ-DM rats that are in a hyperosmotic state with elevated plasma vasopressin levels, GALP mRNA levels were increased by approximately 20-fold in the neural lobe relative to control (n = 4, p < 0.001). The current findings are consistent with a strong tonic influence of leptin receptor signalling on hypothalamic GALP expression under normal conditions, and possible abnormalities in GALP neuronal signalling and their putative targets, thyrotropin-releasing hormone and gonadotropin hormone-releasing hormone neurons, under pathophysiological conditions such as diabetes and obesity. Our data in STZ-DM rats also clearly demonstrate that GALP gene expression is differentially regulated in neurons and pituicytes.

Topics: Analysis of Variance; Animals; Arcuate Nucleus of Hypothalamus; Arginine Vasopressin; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Galanin-Like Peptide; Hypothalamus; In Situ Hybridization; Male; Neuropeptide Y; Obesity; Pituitary Gland; Rats; Rats, Sprague-Dawley; Rats, Zucker; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger

Galanin-like peptide (GALP) is a novel peptide that has been isolated from the porcine hypothalamus. The expression of GALP mRNA is localized to the hypothalamic arcuate nucleus and is thought to be under the regulation of leptin. First, we confirmed by real-time PCR analysis that sc administration of leptin to Wistar rats under food-deprived conditions resulted in a 1.5-fold increase in hypothalamic GALP mRNA levels. Next, GALP mRNA levels were found to be reduced by 50% in 11-wk-old male Zucker obese rats compared with age-matched Zucker lean rats, whereas neuropeptide Y mRNA levels were increased by 55% and proopiomelanocortin mRNA levels were reduced by 53% in Zucker obese rats. Analysis using a two-site enzyme immunoassay revealed a lower level of hypothalamic GALP immunoreactivity in 11-wk-old Zucker obese rats (5.9 fmol/mg protein) than in age-matched Zucker lean rats (19.6 fmol/mg protein). Immunohistochemical studies demonstrated that Zucker obese rats (11 wk old) had a reduced number of GALP immunoreactivity-positive cells (29.4 cells/3 slices) in the arcuate nucleus compared with age-matched Zucker lean rats (115 cells/3 slices). Furthermore, Zucker obese rats showed increased sensitivity to intracerebroventricularly administered GALP compared with Zucker lean rats, in that a lower dose of GALP increased plasma LH levels in male Zucker obese rats, but not in male Zucker lean rats. In addition, a reduction in the level of hypothalamic GALP mRNA was found in db/db and ob/ob mice. The result supports the hypothesis that the hypothalamic GALP gene expression is controlled by leptin signals and suggests possible involvement of GALP in the reproductive abnormalities of the Zucker obese rat.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Disease Models, Animal; Galanin-Like Peptide; Gene Expression; Injections, Intraventricular; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Nerve Tissue Proteins; Neurons; Obesity; Rats; Rats, Wistar; Rats, Zucker; RNA, Messenger; Signal Transduction; Up-Regulation

The effects of leptin upon body weight (BW) cannot be explained by its anorectic actions alone. Part of the metabolic changes elicited by leptin includes sympathetic nervous system activation leading to increased energy expenditure. Galanin-like peptide (GALP), a recently described hypothalamic neuropeptide, is up-regulated by leptin and has anorectic effects in the mouse. We postulated that GALP mediates effects of leptin upon metabolism. To test this hypothesis, we administered GALP centrally to the leptin-deficient ob/ob mouse. Acutely, GALP induced a decrease in food intake and BW, both of which remained significant relative to controls for 4 d. Chronic GALP administration resulted in a sustained decrease in BW and an increase in core body temperature, despite significant recovery of food intake. In a pair-fed model, chronic GALP treatment resulted in a greater decrease in BW than that seen in controls. Furthermore, GALP treatment resulted in increased body temperature and uncoupling protein 1 mRNA and protein in brown adipose tissue compared with controls. The expression of pro-opiomelanocortin (POMC) mRNA in the arcuate nucleus was decreased after chronic GALP treatment. These observations suggest that leptin's activation of the sympathetic nervous system, and ultimately thermogenesis, may be partially mediated by GALP through a melanocortin-independent mechanism.

Topics: Adipose Tissue, Brown; Animals; Arcuate Nucleus of Hypothalamus; Body Weight; Carrier Proteins; Drug Administration Schedule; Eating; Galanin-Like Peptide; Injections, Intraventricular; Ion Channels; Leptin; Male; Membrane Proteins; Metabolism; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Obesity; Pro-Opiomelanocortin; Rats; RNA, Messenger; Sympathetic Nervous System; Uncoupling Protein 1

Galanin-like peptide (GALP) is a newly discovered molecule whose expression in the brain is confined to the arcuate nucleus and median eminence. In the rat, cellular levels of GALP mRNA are reduced by fasting and reversed by peripheral administration of leptin. The purpose of this investigation was 1) to clone and map the distribution of GALP mRNA in the brain of the mouse; 2) to compare the pattern and magnitude of GALP mRNA expression in the leptin-deficient obese (ob/ob) mouse with that of wild-type controls; and 3) to examine the effects of leptin delivered into the brain on the expression of GALP mRNA in the ob/ob mouse. We report the sequence of a mouse GALP cDNA and show that GALP mRNA is expressed in the arcuate nucleus, median eminence, infundibular stalk, and the neurohypophysis of this species. The expression of GALP mRNA in the brain was markedly reduced in the ob/ob mice, compared with wild-type animals. Intracerebroventricular infusion of leptin to ob/ob mice increased both the number of GALP mRNA-expressing neurons and their content of GALP mRNA, compared with vehicle-treated controls. These observations demonstrate that GALP mRNA is induced by leptin through a direct action on the brain.

Topics: Animals; Brain; Cloning, Molecular; DNA, Complementary; Galanin-Like Peptide; Hypothalamus; Leptin; Male; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Obesity; Reference Values; RNA, Messenger; Tissue Distribution