Brain Peptides and Obesity: Pharmacologic Treatment

Leibowitz, Sarah F.

doi:10.1002/j.1550-8528.1995.tb00230.x

Cited by 104 publications

(59 citation statements)

References 189 publications

(176 reference statements)

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“…Many of the areas suffering anterograde degeneration have previously been shown to be involved in various aspects of feeding and/or body weight regulation. These include the lateral septum (55,108), shell area of the nucleus accumbens (61,82,99,100), medial division of the extended amygdala (see below), medial preoptic nucleus (58,63,104), retrochiasmatic area (29), ventromedial hypothalamic area (e.g., 41,48,49), and ventral premammillary nucleus (30,105).…”

Section: Anterograde Degeneration and Retrograde Tracing Experimentsmentioning

confidence: 99%

Obesity-inducing amygdala lesions: examination of anterograde degeneration and retrograde transport

King

Cook

Rossiter

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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King, Bruce M., Jack T. Cook, Kirk N. Rossiter, and Bethany L. Rollins. Obesity-inducing amygdala lesions: examination of anterograde degeneration and retrograde transport. Am J Physiol Regul Integr Comp Physiol 284: R965-R982, 2003. First published November 14, 2002 10.1152/ajpregu.00249.2002.-Small lesions centered in the posterodorsal region of the medial amygdala resulted in excessive weight gains in female rats. Unilateral lesions were nearly as effective as bilateral lesions in the first 48 h after surgery (ϩ21 to ϩ32 g). Assessment of lesion damage was done by both qualitative evaluation and by a quantitative grid-point counting method. The critical sites for weight gain were the intra-amygdaloid bed nucleus of the stria terminalis and the posterodorsal medial amygdaloid nucleus. Incidental damage to the overlying globus pallidus was negatively related to weight gain. The cupric silver method for demonstrating axonal degeneration was applied to brains with obesity-inducing lesions. A dense pattern of degenerating terminals was found in the lateral septum, amygdala, ventral striatum, and ventromedial hypothalamus. Degeneration in the paraventricular nucleus of the hypothalamus was scarce or absent. Small retrograde tracer injections made in either the intra-amygdaloid bed nucleus of the stria terminalis or in the posterodorsal medial amygdaloid nucleus labeled cells in the amygdala, lateral septum, and hypothalamus, reciprocating the anterograde projections from the amygdala to these areas. The data suggest that subdivisions of the posterodorsal amygdala participate in the regulation of feeding in a manner that is similar to the better-known role of this part of the brain in mediating reproductive behavior. Although topographical differences may exist within the amygdaloid and hypothalamic subdivisions regulating these two sexually dimorphic behaviors, the relays engaged by feeding-related connections and those related to reproduction are remarkably parallel. nucleus accumbens; hypothalamus; stria terminalis SEVERAL RECENT STUDIES have demonstrated that bilateral electrolytic lesions of the amygdala in female rats can result in marked hyperphagia and excessive weight gains. Daily food intake nearly doubles, and weight gains of 20-30 g during the first 3 days after lesions are not unusual (e.g., 45, 50-53, 84). Weight gains of Ն100 g in 20-25 days have been observed (50, 51). The lesions result in a marked preference for carbohydrates (53). Although food intake eventually returns to normal, the excessive weight gain is maintained indefinitely, with a marked increase in adipose tissue (50).These results are similar to those reported many years ago for cats, dogs, and primates (including humans) given amygdaloid lesions or temporal lobectomies (e.g., 9, 32, 37, 70, 103). In the rat, the effective lesion site for hyperphagia and obesity has recently been identified as the posterodorsal part of the medial amygdaloid nucleus (MePD) and the intra-amygdaloid bed nucleus of the stria terminalis (BSTIA), together ...

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Section: Anterograde Degeneration and Retrograde Tracing Experimentsmentioning

confidence: 99%

Obesity-inducing amygdala lesions: examination of anterograde degeneration and retrograde transport

King

Cook

Rossiter

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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“…PYY3-36 has high affinity for neuropeptide Y (NPY) Y2 receptors and lower affinity for Y1 and Y5 NPY receptors (Grandt et al, 1992;Ballantyne, 2006); NPY is a hypothalamic peptide that increases food intake after hypothalamic or ventricular injections (Leibowitz, 1995). The Y2 receptor is a putative NPY presynaptic inhibitory autoreceptor, whereas Y1 and Y5 are postsynaptic excitatory receptors (Wahlestedt et al, 1986;Larhammar and Salaneck, 2004).…”

Section: Introductionmentioning

confidence: 99%

Peptide YY3-36 Decreases Reinstatement of High-Fat Food Seeking during Dieting in a Rat Relapse Model

Ghitza¹,

Nair²,

Golden³

et al. 2007

J. Neurosci.

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A major problem in treating obesity is high rates of relapse to maladaptive food-taking habits during dieting. This relapse is often provoked by acute re-exposure to palatable food, food-associated cues, or stress. We used a reinstatement model, commonly used to study relapse to abused drugs, to explore the effect of peptide YY3-36 (PYY3-36) on reinstatement of high-fat (35%, 45 mg pellets) food seeking induced by acute exposure to the pellets (pellet priming), a cue previously associated with pellet delivery (pellet cue), or yohimbine (2 mg/kg, a pharmacological stressor). Rats were placed on a restricted diet (16 g of chow per day) and lever-pressed for the pellets for 9 -12 sessions (6 h/d, every 48 h); pellet delivery was paired with a tone-light cue. They were then given 10 -20 extinction sessions wherein lever presses were not reinforced with the pellets and subsequently tested for reinstatement of food seeking. Finally, systemic PYY3-36 injections had minimal effects on ongoing food self-administration or heroin priming-or heroin cue-induced reinstatement of heroin seeking. These data identify an effect of systemic PYY3-36 on relapse to food seeking that is independent of Y2 receptor activation in Arc and suggest that PYY3-36 should be considered for the treatment of relapse to maladaptive food-taking habits during dieting.

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“…While the subjects in this study had elevated CSF 5-HIAA (data not shown), no significant relationship with CSF GAL was found. In the brain, GAL stimulates appetite and in particular fat consumption (Lee et al 1994;Leibowitz 1995). These data raise the question of whether alterations in brain GAL activity play a role in common clinical symptoms in AN, such as food restriction and fat avoidance (Sunday and Halmi 1990).…”

Section: Discussionmentioning

confidence: 99%

“…The main site of action of brain GAL is the paraventricular nucleus of the HTL as well as other HTL nuclei (Crawley 1999). GAL may stimulate appetite (Lee et al 1994) and in particular fat intake (Leibowitz 1995). GABA has been suggested to be an important part of a system in the brain that constitutes "taste pleasure" (Berridge and Pecina 1995), and may transmit taste information (Yamamoto et al 1998).…”

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confidence: 99%

Could Reduced Cerebrospinal Fluid (CSF) Galanin Contribute to Restricted Eating in Anorexia Nervosa?

Frank

Kaye

Sahu

et al. 2001

Neuropsychopharmacology

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Galanin (GAL) and gamma amino butyric acid (GABA) are orexigenic neuropeptides that could contribute to the pathogenesis of anorexia nervosa (AN). To avoid the confounding effects of the ill state, we studied women who were recovered ( Ͼ 1 year, normal weight, and regular menstrual cycles, no bingeing or purging) from AN (REC AN) and matched healthy control women (NC). CSF GAL was reduced in REC AN (64.4 Ϯ 8.6 pg/ml) compared to NC (72.0 Ϯ 11.6 pg/ml; p Ͻ .05) (American Psychiatric Association 1994). The most distinguishing characteristic of AN is severe emaciation. Two subtypes have been identified. Restrictingtype AN patients lose weight by pure restricted eating. Bulimic anorexics also restrict food, but engage episodically in inappropriate compensatory behaviors, most often repeated bingeing and purging behavior. It has been hypothesized that a disturbance of brain neurotransmitter function might contribute to disturbances of food ingestion in AN. Two neuropeptides of potential interest are galanin (GAL) and gamma amino butyric acid (GABA) since both peptides contribute to the modulation of feeding (Hoebel 1997;Kelley 1999).GAL and GABA are expressed in several hypothalamic sites and they are co-expressed in the hypothalamus (HTL) arcuate nucleus (Kalra et al. 1999). The main site of action of brain GAL is the paraventricular nucleus of the HTL as well as other HTL nuclei (Crawley 1999). GAL may stimulate appetite (Lee et al. 1994) and in particular fat intake (Leibowitz 1995). GABA has been suggested to be an important part of a system in the brain that constitutes "taste pleasure" (Berridge and Pecina 1995), and may transmit taste information (Yamamoto et al. 1998).Disturbances of neuropeptides could be a consequence of disturbed eating behavior or malnutrition, or pre-morbid traits that contribute to a vulnerability to develop an ED. Determining whether abnormalities are a consequence or a potential antecedent of pathological feeding behavior is a major question in the study of eating disorders. It is impractical to study people with ED prospectively due to the young age of onset and diffi- NO . 6 Reduced CSF Galanin and GABA after Recovery from AN 707 culty in premorbid identification of people who will develop an ED. Therefore, we decided to study women who had recovered for more than a year from AN. Any persistent psychobiological abnormalities might be traitrelated and potentially contribute to the pathogenesis of this disorder. In this study we measured CSF values of GAL and GABA in subjects who were long-term recovered from AN (REC AN). We hypothesized that REC AN might have decreased GAL or GABA activity which might contribute to reduced motivation to eat. METHODSSubjects were recruited, screened and diagnosed as previously described (Kaye et al. 1998(Kaye et al. , 1999. Diagnoses were adapted to DSM-IV criteria. REC AN subjects were 18 women who had previously met DSM-IV criteria for AN, 13 women who had recovered from binge eating/purging, and five women who had recovered from restricting ...

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Brain Peptides and Obesity: Pharmacologic Treatment

Cited by 104 publications

References 189 publications

Obesity-inducing amygdala lesions: examination of anterograde degeneration and retrograde transport

Obesity-inducing amygdala lesions: examination of anterograde degeneration and retrograde transport

Peptide YY3-36 Decreases Reinstatement of High-Fat Food Seeking during Dieting in a Rat Relapse Model

Could Reduced Cerebrospinal Fluid (CSF) Galanin Contribute to Restricted Eating in Anorexia Nervosa?

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