Effects of PVN galanin on macronutrient selection

Tempel, Donna L.; Leibowitz, Kimara J.; Leibowitz, Sarah F.

doi:10.1016/0196-9781(88)90265-3

Cited by 241 publications

(106 citation statements)

References 23 publications

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“…This 29-amino acid peptide is found to act similarly to NPY in potentiating food intake after injection into the PVN (236). However, GAL preferentially enhances fat intake (237), in contrast to jVPY's stimulatory action on carbohydrate feeding (Fig. 5).…”

Section: Additional Steroid-peptide Systems Involved In Nutrient Ingementioning

confidence: 97%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

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194

127

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The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle.Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 pg%) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-1 0 pg%) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further ( > 10 pg%) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle.Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term. Moreover, under conditions of obesity, diabetes and food restriction, steroid receptor function is greatly disturbed in association with chronic high circulating levels of CORT and abnormal glucose homeostasis. These disturbances in steroid action, along with dysfunction in brain neurochemical processes, very possibly contribute to the maintenance of hyperphagia and body weight gain in obese and diabetic ...

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Section: Additional Steroid-peptide Systems Involved In Nutrient Ingementioning

confidence: 97%

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Tempel

Leibowitz

1994

J Neuroendocrinology

Self Cite

194

127

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“…The major biological properties of galanin relate to its modulation of hormone and neurotransmitter function with respect to nociception, learning, and memory and in feeding behavior. Galanin's proposed role with respect to satiety is the demonstration that it increases food intake in rodents with a preference for fat diets (Tempel et al, 1988). It is interesting that central administration of neuropeptide Y, another proposed mediator of body weight homeostasis, up-regulates galanin concentrations, potentially augmenting galanin's stimulation of food intake (Crawley et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Molecular Characterization and Expression of Cloned Human Galanin Receptors GALR2 and GALR3

Kolakowski

O’Neill

Howard

et al. 1998

Journal of Neurochemistry

168

129

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Abstract:Galanin is a 29-or 30-amino acid peptide with wide-ranging effects on hormone release, feeding behavior, smooth muscle contractility, and somatosensory neuronal function. Three distinct galanin receptor (GALR) subtypes, designated GALR1, 2, and 3, have been cloned from the rat. We report here the cloning of the human GALR2 and GALR3 genes, an initial characterization of their pharmacology with respect to radioligand binding and signal transduction pathways, and a profile of their expression in brain and peripheral tissues. Human GALR2 and GALR3 show, respectively, 92 and 89% amino acid sequence identity with their rat homologues. Radioligand binding studies with 125l-galanin show that recombinant human GALR2 binds with high affinity to human galanin (K 0 = 0.3 nM). Human GALR3 binds galanin with less affinity (IC50 of 12 nM for porcine galanin and 75 nM for human galanin). Human GALR2 was shown to couple to phospholipase C and elevation of intracellular calcium levels as assessed by aequorin luminescence in HEK-293 cells and by Xenopus melanophore pigment aggregation and dispersion assays, in contrast to human GALR1 and human GALR3, which signal predominantly through inhibition of adenylate cyclase. GALR2 mRNA shows a wide distribution in the brain (mammillary nuclei, dentate gyrus, cingulate gyrus, and posterior hypothalamic, supraoptic, and arcuate nuclei), and restricted peripheral tissue distritution with highest mRNA levels detected in human small intestine. In comparison, whereas GALR3 mRNA was expressed in many areas of the rat brain, there was abundant expression in the primary 01-factory cortex, olfactory tubercie, the islands of Calleja, the hippocampal CA regions of Ammon's horn, and the dentate gyrus. GALR3 mRNA was highly expressed in human testis and was detectable in adrenal gland and pancreas. The genes for human GALR2 and 3 were localized to chromosomes 17q25 and 22q12.2-13.1, respectively. Key Words: Galanin receptor-G protein-coupled receptor-Cloning.

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“…Further, the stimulatory effect of PVN GAL on fat ingestion remains intact in ADX animals and is unaltered by CORT or selective steroid agonists and antagonists (174,175).This relative independence of the PVN GAL system of circulating CORT may be reflective of this peptide's physiological actions in the PVN. These include the inhibition of CORT release (173) and the potentiation of fat ingestion (176). This pattern in the PVN, which contrasts markedly with the NPY system of the ARC, does not preclude a possible interaction between CORT and GAL in otherhypothalamic sites, where glucocorticoidreceptors co-exist with GAL neurons (6,43).…”

Section: Effects Of Adrenal Steroids On Brain Peptide Systems -mentioning

confidence: 99%

“…This suggests a possible relationship between these neurochemical, endocrine, and behavioral phenomena. Since GAL also facilitates copulatory behavior (29) in addition to fat ingestion (176), this peptide may be involved in abroader array of postpubertal behaviors that are essential for reproduction. This is in contrast to NPY, which inhibits sexual behavior (3 9,45) and preferentially stimulates the ingestionof carbohydrate (16 l), whichishighlypreferred by prepubertal subjects.…”

Section: Shifts In Brain Peptides Across Physiological States and Stagesmentioning

confidence: 99%

Brain Peptides and Obesity: Pharmacologic Treatment

Leibowitz

1995

Obesity Research

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104

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LEIBOWITZ, SARAH F. Brain peptides and obesity: pharmacologic treatment. ObesRes. 1995;3(Supp14):573S-5893. Obesity results from an imbalance between nutrient ingestion andmetabolism,withmore calories being ingested than utilized. Thebrain plays animportant roleincoordinating these complex behavioral and physiologicalfunctions, operating through multiple neurochemical systems with distinct properties. This review focuses on two hypothalamicpeptide systems, neuropeptide Y (NPY) and galanin (GAL), that illustrate how the brain operates through different mechanisms to control the body's nutrient stores, in different states o r conditions. These peptides have different behavioralandphysiologicaleffects andare,themselves,differentially responsive to feedback signals from circulating steroids,peptides,and nutrients. They canbedistinguishedby their relation to natural feeding patterns and endogenous hormones and by their specificity of action in relation to natural biological rhythms.Theneuroanatomicalsubstrates involved in these actionsaf NPY and GAL are also distinct. The neurocircuit mediating NPY's actions originates in the arcuatenucleus and terminates in the medial portion of the paraventricular nucleus; the GAGcontaining neurons, in contrast, are concentrated in the lateral portion of the paraventricular nucleus, in addition to the medial preoptic area, which contribute to 1ocalGALinnervation as wellas projections to the median eminence. Regarding their distinct functions, the evidence suggests that the NPY system is more closely related to patterns of carbohydrate ingestion andcarbohydrate utilization, channeling nutrients towards the synthesisoffat. Itismost strongly activatedatthestartoftheactive feeding cycle or afterweaning,in close association with the adrenal steroid,corticosterone. The GAL system,in contrast, is more closely associated with patterns of fat consumption and signals related to fat oxidation. This peptide systemis most active duringthemiddleof the feeding cycle or immediately afterpuberty,in close associationwith the gonadal steroids. The gene expression and synthesis of these peptides in their respective neuronal cell groups is inhibited by circulating insulin and altered by dietary nutriFrom the Rockefeller University, New York, NY

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Effects of PVN galanin on macronutrient selection

Cited by 241 publications

References 23 publications

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Adrenal Steroid Receptors: Interactions with Brain Neuropeptide Systems in Relation to Nutrient Intake and Metabolism

Molecular Characterization and Expression of Cloned Human Galanin Receptors GALR2 and GALR3

Brain Peptides and Obesity: Pharmacologic Treatment

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