Hypothalamic galanin: control by signals of fat metabolism

Wang, Jian; Akabayashi, Akira; Yu, Hi Joon; Dourmashkin, Jordan; Alexander, Jesline T.; Silva, Iván; Lighter, Jennifer; Leibowitz, Sarah F.

doi:10.1016/s0006-8993(98)00632-5

Cited by 64 publications

(39 citation statements)

References 56 publications

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“…These findings suggest a role specifically for processes of fat metabolism in controlling the expression of endogenous PVN GAL. This idea receives support from published evidence, showing similar relationships in rats exposed for brief periods to an HFD vs HCD independent of changes in body fat 6 and demonstrating that pharmacological blockade of fat oxidation reduces PVN GAL mRNA 44 while stimulating PVN GAL-R1 mRNA. 45 Also, reduced fat oxidation induces a feeding response that is blocked by a GAL receptor antagonist.…”

Section: Discussionmentioning

confidence: 57%

Different forms of obesity as a function of diet composition

et al. 2005

Int J Obes

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OBJECTIVE:To characterize the phenotype of obesity on a high-carbohydrate diet (HCD) as compared to a high-fat diet (HFD) or moderate-fat diet (MFD). METHODS AND PROCEDURES:In four experiments, adult Sprague-Dawley rats (275-300 g) were maintained for several weeks on a: (1) HFD with 50% fat; (2) balanced MFD with 25% fat; or (3) HCD with 10% fat/65% carbohydrate. Then, based on the amount of body fat accumulated in four dissected fat pads, the animals were subgrouped as lean (lowest tertile) or obese (highest tertile) and characterized with multiple measures. RESULTS: The obese rats of these diet groups, with 70-80% greater body fat than the lean animals, exhibited elevated levels of leptin and insulin and increased activity of lipoprotein lipase in adipose tissue (aLPL), with no change in muscle LPL. Characteristics common to the obese rats on the HFD or MFD, but not seen on the HCD, were hyperphagia, elevated circulating levels of triglycerides (TG), nonesterified fatty acids (NEFA) and glucose, and a significant increase in b-hydroxyacyl-CoA dehydrogenase (HADH) activity in muscle, reflecting its greater capacity to metabolize fat. This was accompanied by a significant increase in expression of the peptide, galanin (GAL), in the paraventricular nucleus (PVN), as measured by in situ hybridization and real-time quantitative PCR, and also in GAL peptide immunoreactivity. These measures of GAL were consistently, positively correlated with circulating TG levels and also with HADH activity in muscle. In contrast to these fatassociated changes, rats that became obese on an HCD maintained normal caloric intake and levels of TG, NEFA, and glucose. They also showed no change in PVN GAL mRNA or peptide. Instead, they exhibited a significant reduction in HADH activity compared to the lean animals, along with increased activity of phosphofructokinase in muscle, a key enzyme in glycolysis. CONCLUSION: Specific characteristics of obesity, including expression of hypothalamic peptides, are dependent upon diet composition. Whereas obesity on an HFD is associated with hyperphagia and elevated lipids, fat metabolism in muscle, and fatstimulated peptides such as GAL, obesity on an HCD with a similar increase in body fat shows none of these characteristics and instead exhibits a metabolic pattern in muscle that favors carbohydrate over fat oxidation. These results suggest the existence of multiple forms of obesity with different underlying mechanisms that are diet dependent.

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Section: Discussionmentioning

confidence: 57%

Different forms of obesity as a function of diet composition

et al. 2005

Int J Obes

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“…Notably, chronic intracerebroventricular administration of galanin did not induce sustained obesity, but chronic daily administration of galanin into the PVN produced variable, complex changes in daily caloric intake, levels of obesity, and regional fat deposition, depending on the fat and carbohydrate content of the diet (Smith et al, 1994). Rats fed a high-fat, but not high-carbohydrate or -protein, diet displayed a marked increase in hypothalamic galanin levels (Leibowitz et al, 1998), and blockade of fatty acid metabolism reduced galanin expression in the anterior PVN (Wang et al, 1998a), suggesting galanin production is regulated by signals related to fatty acid metabolism (Barson et al, 2010). Acute effects of galanin on feeding were abolished by galanin receptor (Corwin et al, 1993) and a 2 -adrenoceptor (Kyrkouli et al, 1990a) antagonists.…”

Section: A Feeding and Energy Homeostasismentioning

confidence: 96%

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

et al. 2014

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“…3,7,36,45 Information about the status of fat reserves is communicated throughout the body by the adipocyte-derived hormone leptin, which is secreted into the general circulation. The CNS is a major target for leptin's action and long form leptin receptor (Ob-Rb) mRNA is expressed by neurons in distinct anatomical regions of the brain.…”

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confidence: 99%

Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus

et al. 2001

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AbstractÐGalanin is widely distributed throughout the mammalian brain and has been implicated in the regulation of food intake, metabolism and reproductionÐfunctions that are also thought to be under the control of leptin. To investigate the possible role of galanin in mediating the physiological effects of leptin in the mouse, we had three experimental objectives: ®rst, to map the distribution of galanin messenger RNA-expressing cells in the brain of the mouse; second, to assess the effects of leptin on galanin gene expression in areas of the brain thought to be involved in the regulation of body weight and reproduction; and third, to determine whether galanin neurons in these regions express leptin receptor messenger RNA. We found the pattern of galanin messenger RNA expression in the mouse brain to be similar, but not identical, to that in the rat. Leptin treatment (2 mg/g for six days) signi®cantly reduced cellular levels of galanin messenger RNA in the hypothalamic periventricular nucleus of leptin-de®cient obese (ob/ob) mice (P , 0.01) by approximately 30%; however, leptin did not appear to in¯uence the expression of galanin in the arcuate or dorsomedial nucleus of the hypothalamus. Galanin-producing neurons in the arcuate, dorsomedial and periventricular nuclei did not appear to express leptin receptor messenger RNA (P . 0.05).These results demonstrate that galanin distribution patterns in the mouse brain are comparable to other species and, yet, possess unique features. In addition, galanin-expressing neurons in the hypothalamic periventricular nucleus are targets for regulation by leptin; however, the effect of leptin on galanin gene expression is likely to be mediated indirectly, perhaps through either proopiomelanocortin-or neuropeptide Y-expressing cells in the hypothalamus. q 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.Key words: neuropeptide, gene regulation, neuroanatomy, in situ hybridization, leptin receptor.Galanin is a 29 amino acid neuropeptide that was originally isolated from the porcine gut. 42 In mammals, galanin is widely distributed throughout the central and peripheral nervous systems. 26 One curious observation about galanin's expression in the brain of mammals is its species speci®city, which is particularly evident in the rat and monkey. For example, in the rat there is little or no expression of galanin in the hippocampus but there are abundant galanin-containing cells in the dorsal raphe. 23,34 In the monkey, however, galanin producing cells are found throughout the hippocampus, yet are absent from the dorsal raphe. 17 To date, there has been no detailed mapping of the distribution of galanin in the mouse brain. Because of the growing importance of the mouse as a genetic model for understanding the brain, it is vital that we know the comparative anatomy of neuropeptide expression in the murine brain and use this information to shed light on the differences and similarities between species. The ®rst objective of this study was to complete a detailed map of the...

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Hypothalamic galanin: control by signals of fat metabolism

Cited by 64 publications

References 56 publications

Different forms of obesity as a function of diet composition

Different forms of obesity as a function of diet composition

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus

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