a-MSH enhances activity-based anorexia

Hillebrand, J.J.G.; Kas, Martien; Adan, Roger A.H.

doi:10.1016/j.peptides.2004.11.027

Cited by 33 publications

(18 citation statements)

References 52 publications

(60 reference statements)

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Section: Resultsmentioning

confidence: 99%

“…Animal models of ABA mimic core features of AN in humans, including food restriction, reduced body weight, and enhanced physical activity [24], [25], [30]. We adapted the rat ABA paradigms [23], [24], [25] to our present mouse study. Variations in ABA paradigm or mouse strain or sex can affect food intake and body weight loss [31], [32], [33], [34], [35], [36].…”

Section: Resultsmentioning

confidence: 99%

“…CLAMS (Comprehensive Laboratory Animal Monitoring System) (Columbus Instruments, Columbus, OH) was used to measure body weight, whole-body metabolism [VO 2 , VCO 2 , respiratory exchange ratio (RER), and energy expenditure (EE)], ambulatory activity, running wheel activity, water consumption, and food intake. We adapted the rat ABA paradigm [23], [24], [25] to our present mouse study. As a control, the ad libitum group (AL) was provided access to standard laboratory chow with no running wheel.…”

Section: Methodsmentioning

confidence: 99%

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A Central Role for C1q/TNF-Related Protein 13 (CTRP13) in Modulating Food Intake and Body Weight

et al. 2013

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C1q/TNF-related protein 13 (CTRP13), a hormone secreted by adipose tissue (adipokines), helps regulate glucose metabolism in peripheral tissues. We previously reported that CTRP13 expression is increased in obese and hyperphagic leptin-deficient mice, suggesting that it may modulate food intake and body weight. CTRP13 is also expressed in the brain, although its role in modulating whole-body energy balance remains unknown. Here, we show that CTRP13 is a novel anorexigenic factor in the mouse brain. Quantitative PCR demonstrated that food restriction downregulates Ctrp13 expression in mouse hypothalamus, while high-fat feeding upregulates expression. Central administration of recombinant CTRP13 suppressed food intake and reduced body weight in mice. Further, CTRP13 and the orexigenic neuropeptide agouti-related protein (AgRP) reciprocally regulate each other’s expression in the hypothalamus: central delivery of CTRP13 suppressed Agrp expression, while delivery of AgRP increased Ctrp13 expression. Food restriction alone reduced Ctrp13 and increased orexigenic neuropeptide gene (Npy and Agrp) expression in the hypothalamus; in contrast, when food restriction was coupled to enhanced physical activity in an activity-based anorexia (ABA) mouse model, hypothalamic expression of both Ctrp13 and Agrp were upregulated. Taken together, these results suggest that CTRP13 and AgRP form a hypothalamic feedback loop to modulate food intake and that this neural circuit may be disrupted in an anorexic-like condition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A Central Role for C1q/TNF-Related Protein 13 (CTRP13) in Modulating Food Intake and Body Weight

et al. 2013

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“…Hence, autoAbs against ␣-MSH appear to be relevant to these symptoms, and the most likely route seems to be interference with the central melanocortin system. In fact, the dysregulation of the central melanocortin system may result in psychobehavioral abnormalities characteristic for eating disorders, because critical involvement of melanocortins in the central control of appetite and body weight is well known (9)(10)(11)(12)31), and, besides the control of appetite, melanocortins are involved in variety of motivated behavior (32) and affective states (33)(34)(35). The mechanism of possible autoAbs interference with the melanocortin system may include a direct blockage of melanocortin receptors (as we observed in our in vitro study) by ␣-MSH-autoAbs complexes, rendering them inaccessible for orexigenic agouti-related protein (36) or by complementmediated damage to the cells bearing the peptide-receptor complex.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies against neuropeptides are associated with psychological traits in eating disorders

Fetissov

Harro

Jaanisk

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

133

100

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Previously, we identified that a majority of patients with anorexia nervosa (AN) and bulimia nervosa (BN) as well as some control subjects display autoantibodies (autoAbs) reacting with ␣-melanocyte-stimulating hormone (␣-MSH) or adrenocorticotropic hormone, melanocortin peptides involved in appetite control and the stress response. In this work, we studied the relevance of such autoAbs to AN and BN. In addition to previously identified neuropeptide autoAbs, the current study revealed the presence of autoAbs reacting with oxytocin (OT) or vasopressin (VP) in both patients and controls. Analysis of serum levels of identified autoAbs showed an increase of IgM autoAbs against ␣-MSH, OT, and VP as well as of IgG autoAbs against VP in AN patients when compared with BN patients and controls. Further, we investigated whether levels of these autoAbs correlated with psychological traits characteristic for eating disorders. We found significantly altered correlations between ␣-MSH autoAb levels and the total Eating Disorder Inventory-2 score, as well as most of its subscale dimensions in AN and BN patients vs. controls. Remarkably, these correlations were opposite in AN vs. BN patients. In contrast, levels of autoAbs reacting with adrenocorticotropic hormone, OT, or VP had only few altered correlations with the Eating Disorder Inventory-2 subscale dimensions in AN and BN patients. Thus, our data reveal that core psychobehavioral abnormalities characteristic for eating disorders correlate with the levels of autoAbs against ␣-MSH, suggesting that AN and BN may be associated with autoAb-mediated dysfunctions of primarily the melanocortin system.anorexia ͉ autoimmunity ͉ behavior ͉ bulimia ͉ hypothalamus N europeptides are important transmitters in the brain limbic and neuroendocrine systems involved in the regulation of different modalities of feeding, social and defensive behaviors, the stress response, and homeostasis (1). These roles of neuropeptides suggest a possible implication in some neuropsychiatric conditions primarily manifested by behavioral abnormalities (2, 3), including anorexia nervosa (AN) and bulimia nervosa (BN) (4). Although changes in concentrations of some neuropeptides in plasma or in cerebrospinal fluid have been noted in patients with eating disorders (5, 6), the mechanisms underlying these changes are unknown, and the modern therapy of eating disorders adopts the symptomatic approach (7).In search of possible peptidergic mechanisms underlying eating disorders, we recently found that a majority of a group of Swedish AN and BN patients display autoAbs against ␣-melanocyte-stimulating hormone (␣-MSH) (8), a melanocortin peptide involved in appetite control (9-12). AutoAbs against adrenocorticotropic hormone (ACTH) and luteinizing hormone-releasing hormone (LHRH) also were identified in some patients and controls (8). The growing evidence of the immune system's critical involvement in some neurological and psychiatric disorders (13) suggests that autoAbs reacting with neuropeptides responsible for the c...

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“…It is one of the downstream pathways mediating the regulation of energy homeostasis by leptin and insulin (Schwartz et al, 2000;Benoit et al, 2002). ␣-MSH released by proopiomelanocortin (POMC) neurons is considered an anorexigenic peptide, which can increase energy expenditure (Poggioli et al, 1986;Brown et al, 1998;Hillebrand et al, 2005). MC3/4R agonists inhibit feeding, whereas the antagonists stimulate feeding (Cowley et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Pol²

2008

J. Neurosci.

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Anorexigenic melanocortins decrease food intake by activating MC3/MC4 receptors (MC3/4R); the prevailing view is that the orexigenic neuropeptide agouti-related peptide (AgRP) exerts the opposite action by acting as an antagonist at MC3/MC4 receptors. A total of 370 hypothalamic ventromedial nucleus (VMH) glutamatergic neurons was studied using whole-cell recording in hypothalamic slices from a novel mouse expressing green fluorescent protein (GFP) under control of the vesicular glutamate transporter 2 (vGluT2) promoter. Massive numbers of GFP-expressing VMH dendrites extended out of the core of the nucleus into the surrounding cell-poor shell. VMH dendrites received frequent appositions from AgRP-immunoreactive axons in the shell of the nucleus, but not the core, suggesting that AgRP may influence target VMH neurons. ␣-MSH, melanotan II (MTII), and selective MC3R or MC4R agonists were all inhibitory, reducing the spontaneous firing rate and hyperpolarizing vGluT2 neurons. The MC3/4R antagonist SHU9119 was excitatory. Unexpectedly, AgRP did not attenuate MTII actions on these neurons; instead, these two compounds showed an additive inhibitory effect. In the absence of synaptic activity, no hyperpolarization or change in input resistance was evoked by either MTII or AgRP, suggesting indirect actions. Consistent with this view, MTII increased the frequency of spontaneous and miniature IPSCs. In contrast, the mechanism of AgRP inhibition was dependent on presynaptic inhibition of EPSCs mediated by G i /G o -proteins, and was attenuated by pertussis toxin and NF023, inconsistent with mediation by G s -proteins associated with MC receptors. Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors.

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a-MSH enhances activity-based anorexia

Cited by 33 publications

References 52 publications

A Central Role for C1q/TNF-Related Protein 13 (CTRP13) in Modulating Food Intake and Body Weight

A Central Role for C1q/TNF-Related Protein 13 (CTRP13) in Modulating Food Intake and Body Weight

Autoantibodies against neuropeptides are associated with psychological traits in eating disorders

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

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