Leptin Treatment in Activity-Based Anorexia

Hillebrand, J.J.G.; Koeners, Maarten P.; Rijke, Corine E de; Kas, Martien; Adan, Roger A.H.

doi:10.1016/j.biopsych.2005.03.011

Cited by 87 publications

(68 citation statements)

References 42 publications

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“…Previously, we observed that physical activity per se does not result in up-regulation of POMC gene expression (Hillebrand et al, 2005c;. One may argue that circadian fluctuation of POMC mRNA expression can also play a role in up-regulation of POMC.…”

Section: Discussionmentioning

confidence: 80%

AgRP(83–132) and SHU9119 differently affect activity-based anorexia

Hillebrand

Kas

Scheurink

et al. 2006

European Neuropsychopharmacology

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Activity-based anorexia (ABA) mimics starvation and hyperactivity of anorexia nervosa patients in rats. Activation of the melanocortin (MC) system leads to hypophagia and increased energy expenditure in ad libitum fed rats. Therefore, activation of the MC system might underlie the development and propagation of ABA. Pro-opiomelanocortin (POMC) gene expression is normally decreased during negative energy balance. Strikingly, we found a transient up-regulation of POMC mRNA levels in the arcuate nucleus during the development of ABA, indicating a hyperactive MC system. However, wheel running and food intake were not influenced by treating ABA rats with the competitive antagonist SHU9119. This suggests that agonism of MC receptors by endogenous a-melanocyte-stimulating hormone (a-MSH) levels does not underlie ABA. Instead, treatment with the inverse agonist AgRP did ameliorate signs of ABA. This implies that modulation of constitutive MC receptor activity rather than antagonizing putative a-MSH release contributes to the development and propagation of ABA.

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Section: Discussionmentioning

confidence: 80%

AgRP(83–132) and SHU9119 differently affect activity-based anorexia

Hillebrand

Kas

Scheurink

et al. 2006

European Neuropsychopharmacology

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“…Conversely, leptin administration decreases wheel running in rats (Hillebrand et al 2005). Gelegen et al (2007) compared the C57BL/6J and DBA/2J strains of inbred mice, which display low and high levels of anxiety and activity-related behaviors, respectively, in the activity/stress model.…”

Section: Animal Models Of Anmentioning

confidence: 98%

Relevance of animal models to human eating disorders and obesity

2008

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Background and rationale This review addresses the role animal models play in contributing to our knowledge about the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) and obesity. Objectives Explore the usefulness of animal models in complex biobehavioral familial conditions, such as AN, BN, and obesity, that involve interactions among genetic, physiologic, psychological, and cultural factors. Results and conclusionsThe most promising animal model to mimic AN is the activity-based anorexia rodent model leading to pathological weight loss. The paradigm incorporates reward elements of the drive for activity in the presence of an appetite and allows the use of genetically modified animals. For BN, the sham-feeding preparation in rodents equipped with a gastric fistula appears to be best suited to reproduce the postprandial emesis and the defects in satiety. Animal models that incorporate genes linked to behavior and mood may clarify biobehavioral processes underlying AN and BN. By contrast, a relative abundance of animal models has contributed to our understanding of human obesity. Both environmental and genetic determinants of obesity have been modeled in rodents. Here, we consider single gene mutant obesity models, along with models of obesigenic environmental conditions. The contributions of animal models to obesity research are illustrated by their utility for identifying genes linked to human obesity, for elucidating the pathways that regulate body weight and for the identification of potential therapeutic targets. The utility of these models may be further improved by exploring the impact of experimental manipulations on the behavioral determinants of energy balance.

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“…This key role of leptin in SIH has recently been confirmed in an independent study. 104 Accordingly, hypoleptinaemia can trigger a strong behavioural response, which can be corrected via increments of circulating leptin levels.…”

Section: Hyperactivitymentioning

confidence: 99%

“…107 Nevertheless, it has been suggested that a hyperactive melanocortinergic system underlies the SIH phenotype. 104,105,107 Other possible effectors downstream of the leptin receptor that might be implicated in SIH are the serotonergic and/or dopaminergic system as well as the hypothalamic-pituitary adrenal axis.…”

Section: Hyperactivitymentioning

confidence: 99%

The role of leptin in anorexia nervosa: clinical implications

et al. 2006

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Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with this eating disorder are related to the low leptin levels, which are characteristic of acute AN. Weight gain in AN patients can induce relative hyperleptinaemia in comparison to controls matched for body mass index; circulating leptin concentrations in AN patients thus transverse from subnormal to supranormal levels within a few weeks. We review findings on leptin secretion in AN and focus on implications, particularly for the hypothalamus-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Undoubtedly, the elucidation of leptin's function as a trigger of diverse neuroendocrine adaptations to a restricted energy intake has substantially advanced our knowledge of the pathogenesis of distinct symptoms of AN, including amenorrhoea that represents one of the four diagnostic criteria. The fact that hypoleptinaemia can induce hyperactivity in a rat model for AN has led to a series of studies in AN patients, which support the notion that application of leptin to severely hyperactive patients might prove beneficial.

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Leptin Treatment in Activity-Based Anorexia

Abstract: Background: Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN).

Cited by 87 publications

References 42 publications

AgRP(83–132) and SHU9119 differently affect activity-based anorexia

AgRP(83–132) and SHU9119 differently affect activity-based anorexia

Relevance of animal models to human eating disorders and obesity

The role of leptin in anorexia nervosa: clinical implications

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