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Obesity Related Peptide
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Galanin related products |
Differential Patterns of Fos Induction in the Hypothalamus of the Rat following central injection of Galanin-like Peptide and Galanin
Galanin and its newly discovered relative galanin-like peptide (GALP) are neuropeptides that are implicated in the neuroendocrine regulation of body weight and reproduction. GALP has been shown to bind in vitro to galanin receptor subtypes 1 and 2, but whether it has its own specific receptor(s) is unknown. We reasoned that if GALP acts through a receptor that is distinct from galanin receptors, then GALP should activate central pathways that are different from those activated by galanin. The purpose of this study was to determine whether galanin and GALP produce different patterns of neuronal activation within the hypothalamus. Quantitative analysis of Fos immunoreactivity showed that galanin induced a significantly greater number of Fos-positive nuclei in the paraventricular nucleus compared with GALP (P < 0.001); however, compared with galanin, GALP induced significantly more Fos-positive cells in the horizontal limb of the diagonal band of Broca, caudal preoptic area, arcuate nucleus, and median eminence (P < 0.05). These observations suggest that GALP and galanin act through different receptor-mediated pathways to exert their effects on the regulation of body weight and reproduction and identify target cells for GALP's specific actions in the hypothalamus, including the preoptic area, paraventricular and arcuate nuclei, and the median eminence.
Fraley GS et al. Endocrinology, Apr 2003; 144:
1143 - 1146
Role of neuropeptide Y and galanin in high altitude induced anorexia
in rats
Anorexia causing weight loss at high altitude (HA) is a major problem.
Neuropeptide Y (NPY) and galanin are considered to have appetite regulatory
function. The present study was therefore undertaken to investigate the
changes in these two peptides at simulated HA and its possible role in
anorexia. Male Sprague-Dawley rats (n = 8 in each group) were exposed
to simulated HA (7620 m) for 1, 7, 14 and 21 days for 6 h a day and to
an altitude of 6,096 m for 72 h to study the effect of intermittent and
continuous exposure, respectively. NPY and galanin levels were estimated
in different brain parts and plasma of exposed and unexposed control animals.
Significant reduction in food intake was observed in rats during both
intermittent as well as continuous exposure. In case of 72 h continuous
exposure severe reduction in food intake was observed (73.2%) with reduction
in body mass (approximately 29.7g/rat in 48h). Hypothalamic NPY levels
were decreased by 54.7, 35.0 and 15.4% in 1, 7, and 14 days, respectively,
in case of intermittent exposure to HA. However in case of 72 h HA exposure
no significant change in hypothalamic and circulating NPY levels were
observed. Plasma galanin levels were decreased in both intermittent and
72 h continuous HA exposed rats. Hypothalamic galanin levels were also
decreased in 72h exposed rats. The changes in levels of these peptides
may be responsible for anorexia at HA.
Singh SN, Vats P, Shyam R, Suri S, Kumria MM,
Ranganathan S, Sridharan K, Selvamurthy W. Nutr Neurosci 2001;4(4):323-31
Plasma leptin and hypothalamic neuropeptide Y and galanin levels
in Long-Evans rats with marked dietary preferences.
Neuropeptides present in the hypothalamus and new messengers in the periphery
such as leptin modulate food intake in mammals. Neuropeptide Y (NPY) and
galanin in microdissected brain areas and plasma leptin levels were measured
by specific radioimmunoassays during the resting period in rats selected
for their strong preference either for carbohydrate or fat, but with identical
energy intake. NPY concentrations were 23% lower (p <.02) in carbohydrate-preferring
(CP) than in fat-preferring (FP) rats in the parvocellular part of the
paraventricular nucleus (PVN), which is one of the main areas involved
in the regulation of feeding behavior. On the other hand, galanin was
significantly (+25%, p = .03) higher in CP rats than in FP rats in the
magnocellular part of the PVN. Plasma leptin was more than 50% higher
in FP rats than in CP rats (p < .01) and highly correlated with the
fat preference (r = 0.57; p = .003) and body weight gain. We conclude
that the rats with a spontaneous and marked dietary preference have a
characteristic peptidergic profile. Due to their anatomical relationships,
neuropeptide Y could act in conjunction with galanin in a peptidergic
balance located in the paraventricular nucleus. This model integrates
information provided by the energy stores and translated by peripheral
messengers such as leptin which could act in a counterregulatory manner
in order to limit the overweight induced by the ingestion of unbalanced
diets.
Beck B, Stricker-Krongrad A, Burlet A, Cumin F,
Burlet C. Plasma leptin and hypothalamic neuropeptide Y and galanin levels
in Long-Evans rats with marked dietary preferences. Nutr Neurosci 2001;4(1):39-50
Interplay between galanin and leptin in the hypothalamic control of feeding via corticotropin-releasing hormone and neuropeptide Y
Over long periods, feeding and metabolism are tightly regulated at the
central level. The total amount of nutrients ingested is thought to result
from a delicate balance between orexigenic and anorexigenic factors expressed
and secreted by specialized hypothalamic neuronal populations. We have
developed a system of perifused hypothalamic neurons to characterize the
relationships existing between the orexigenic peptide galanin and two
other physiological modulators of feeding: neuropeptide Y (NPY) and corticotropin-releasing
hormone (CRH). We demonstrated that galanin stimulates CRH and NPY secretion
from hypothalamic neurons in a dose-dependent manner. Exposure to leptin
for 24 h before galanin stimulation decreased NPY secretion by 30%, leaving
the responsiveness of CRH neurons intact. These results suggest that CRH
and NPY neurons participate to the intrahypothalamic signaling pathway
of galanin, an observation that can explain the lower potency of galanin
to stimulate food intake in vivo compared with NPY. The differential effects
exerted by leptin on CRH and NPY suggest that there exists a subset of
NPY neurons that are exquisitely sensitive to marked variations in leptin
levels, and that the CRH neurons are less responsive to increases in leptin
concentrations.
Bergonzelli GE, Pralong FP, Glauser M, Cavadas C,
Grouzmann E, Gaillard RC. Diabetes 2001 Dec;50(12):2666-72
Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction?
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.
Gundlach AL. Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction? Eur J Pharmacol 2002 Apr 12;440(2-3):255-68
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Galanin related products |