Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity

Smith, Brenda K.; York, David A.; Bray, George A.

doi:10.1016/0196-9781(94)90152-x

Cited by 93 publications

(38 citation statements)

References 20 publications

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“…56 The GAL-stimulated feeding response is stronger and more prolonged in subgroups or strains of rats that naturally prefer fat or are maintained on an HFD compared to an HCD. 53,57 Also, chronic GAL injections, while having little impact on body weight on an HCD with 10% fat, 58 can significantly increase fat pad weights on an HFD with 50-60% fat and can produce a rise in leptin, TG, and NEFA levels together with aLPL activity. 29 Thus, under physiological conditions, the role of GAL in eating and body weight regulation may be expressed only on fat-rich diets.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

Different forms of obesity as a function of diet composition

et al. 2005

Int J Obes

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“…The saline group body weight fell on day +1, and this weight was maintained during the entire study period. Other investigators (47,48), have previously observed a maintenance of body weight in a saline-injected control group. No significant difference in body weight was observed between the saline and AGRP pair-fed groups throughout the study (day +7 body weight: 271 ± 6 [saline] vs. 260 ± 4 g [AGRP pair-fed]; NS) (Fig.…”

Section: ± 07 [Agrp Ad Libitum Fed] Vs ± 09 G [Agrp Pair-fed])mentioning

confidence: 99%

Effects of Chronic Central Nervous System Administration of Agouti-Related Protein in Pair-Fed Animals

Small

Kim²,

Stanley³

et al. 2001

Diabetes

146

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The melanocortin receptor (MC3-R and MC4-R) antagonist, agouti-related protein (AGRP), is a potent stimulant of food intake. We examined the effect of chronic intracerebroventricular (ICV) AGRP treatment on energy metabolism and pituitary function in ad libitum fed rats and rats administered AGRP and then pair-fed to a saline control group. Chronic ICV AGRP (83-132) administration (1 nmol/day for 7 days) significantly increased food intake and body weight in ad libitum fed animals compared with saline-treated controls (body weight on day 7: 272 ± 6 [saline] vs. 319 ± 8 g [AGRP ad libitum fed]; P < 0.001). A significant increase in the epididymal fat pad weight, interscapular brown adipose tissue (BAT) weight, and plasma leptin was also observed in the ad libitum fed group. In the AGRP pair-fed group, a significant increase in the epididymal fat pad weight, BAT weight, and plasma leptin was again observed, suggesting that AGRP caused metabolic changes independent of increased food intake. BAT uncoupling protein 1 (UCP-1) content was significantly decreased compared with saline controls in both the AGRP ad libitum fed (21 ± 8% of saline control; P < 0.01) and AGRP pair-fed groups (24 ± 7% of saline control; P < 0.01). Plasma thyroid-stimulating hormone (TSH) was significantly suppressed compared with saline controls in both the AGRP ad libitum fed and AGRP pair-fed groups (3. T he hypothalamic melanocortin system is a regulator of energy homeostasis. The agouti-related protein (AGRP), produced in the arcuate nucleus, is an antagonist at the melanocortin 3 and 4 receptors (MC3-R and MC4-R), which are distributed throughout the brain. The proopiomelanocortin (POMC) products, such as ␣-melanocyte-stimulating hormone (␣-MSH), act as agonists at the melanocortin receptors (1-3). Hypothalamic POMC mRNA, AGRP mRNA, and the density of MC4-R have been shown to be altered with nutritional status (4,5). Defects of POMC processing and mutations of MC4-R in humans and mice are associated with gross obesity (6-11).5Administration of the synthetic MC3/4-R agonist MT II into the forebrain ventricles or directly into the paraventricular nucleus (PVN) of the hypothalamus of rats or mice produced a dosage-dependent reduction in food intake and body weight (12)(13)(14). A single injection of either the endogenous (AGRP ) or the synthetic (SHU9119 and HS014) MC3/4-R antagonists stimulated food intake in rodents (12,13,15,16). Chronic administration of the more selective MC4-R antagonist, HS028, for 7 days via an osmotic minipump significantly increased food intake and body weight. Tachyphylaxis to HS028 did not occur. However, neither energy expenditure nor pituitary function were examined in this study (17). Previous results from this department have demonstrated that AGRP (83-132), the endogenous hypothalamic melanocortin receptor antagonist, significantly increased 24-h food intake and antagonized the anorectic effects of ␣-MSH (16).The melanocortin system also influences energy expenditure. Intracerebroventricular (ICV) administra...

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“…Throughthesemetabolic actions, as well asthe daily hyperphagiafor carbohydrate and to a lesser extent fat, chronic NPY stimulation increases lipogenesis and body weight gain; it mimics the endocrine and metabolic changes associated with obesity (159,162,195,196). While repeated ventricular injections of GAL produce overeating in the inactive period of the daily cycle, compensatory adjustments during the feeding period preclude alterations in total caloric intakeand weightgain (158).…”

Section: Physiological and Behavioral Effects Of Brain Peptidesmentioning

confidence: 99%

“…This suggests that they may have differential roles in the normal process of energy homeostasis and body weight control. In understanding the functions of these peptides, it will be important to consider the potent effects of the circulating hormones, not only on carbohydrate and lipid metabolism (52,53,153,185) (158). Structure-function analyses of these peptides' feeding stimulatory effects reveal pharmacological specificity in terms of the amino acid sequence required for efficacy.…”

Section: Physiological and Behavioral Effects Of Brain Peptidesmentioning

confidence: 99%

Brain Peptides and Obesity: Pharmacologic Treatment

Leibowitz

1995

Obesity Research

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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Chronic cerebroventricular galanin does not induce sustained hyperphagia or obesity

Cited by 93 publications

References 20 publications

Different forms of obesity as a function of diet composition

Different forms of obesity as a function of diet composition

Effects of Chronic Central Nervous System Administration of Agouti-Related Protein in Pair-Fed Animals

Brain Peptides and Obesity: Pharmacologic Treatment

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