Leptin Treatment in Activity-Based Anorexia

Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
Biological Psychiatry (Impact Factor: 10.26). 08/2005; 58(2):165-71. DOI: 10.1016/j.biopsych.2005.03.011
Source: PubMed


Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa (AN). In ABA, scheduled feeding together with voluntary access to a running wheel results in increased running wheel activity (RWA), hypophagia, and body weight loss. Previously it was shown that leptin treatment reduced semi-starvation-induced hyperactivity in rats. The present study was performed to confirm and extend this finding, to evaluate leptin's effect on energy balance in ABA.
The effects of chronic leptin treatment (intracerebroventricular, 4 microg/day) in ABA rats, ad libitum-fed running rats, and sedentary rats exposed to ad libitum feeding or scheduled feeding were investigated.
Leptin treatment decreased RWA in ABA rats. Additionally, leptin treatment reduced food intake and increased energy expenditure by thermogenesis in ABA rats. Ad libitum-fed running/sedentary rats or food-restricted sedentary rats did not reduce activity after leptin treatment, whereas all leptin-treated rats showed hypophagia. Body temperature was slightly increased in leptin-treated food-restricted sedentary rats.
Although leptin treatment reduced RWA in ABA rats, it also prevented hypothermia and decreased food intake. Altogether, this resulted in a stronger negative energy balance and body weight loss in leptin-treated ABA rats.

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    • "Leptin plays pleiotropic roles in energy assessment and expenditure. When animals are food deprived, and as a consequence develop hyperactivity, leptin injections diminish their activity level [31–33]. As a consequence, leptin levels were hypothesized to be inversely related to the heightened activity levels in ED. "
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    ABSTRACT: Patients with anorexia nervosa (AN) are often observed to have high levels of physical activity, which do not necessarily diminish after a successful therapy. Previous studies have shown that body fat tissue recovery in these patients is associated with a disproportional restoration of the adipocyte hormone, leptin. Therefore, we wondered whether the individual variation in physical activity in AN patients prior to treatment may be related to body fat percentage and plasma leptin level outcome. Body fat percentage, leptin serum, and physical activity levels (accelerometer) were measured in adolescents with an (n=37, age 13 to 17.5 years) at initial assessment, at the end of study participation (median 12 months), and at one-year follow-up. ACCELEROMETER DATA WERE USED TO SPLIT THE PATIENTS IN TWO GROUPS: those with low (n=26) and those with high levels of physical activity (HLPA, n=11). These groups did not differ in terms of age, IQ, presence of menses, BMI and season of admission. The HLPA group was characterized by a longer total duration of illness. Physical activity levels during therapy decreased for the group with initially HLPA and increased for the group with low levels of physical activity (to comparable levels). Physical activity remained stable after one year. The increase in body fat percentage and leptin levels were dependent on the recovery status; however, recovered patients with initially HLPA had significantly higher fat mass during the follow-up. HLPA, an important modulator of AN progression in adolescents, can be successfully diminished by therapeutic intervention. Among recovered patients, those with initially HLPA had higher fat mass levels than those with low levels of physical activity. This finding suggests that HLPA are an important modulator of the body composition recovery mechanism.
    PLoS ONE 10/2013; 8(10):e78251. DOI:10.1371/journal.pone.0078251 · 3.23 Impact Factor
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    • "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]. "
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    ABSTRACT: 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.
    PLoS ONE 04/2013; 8(4):e62862. DOI:10.1371/journal.pone.0062862 · 3.23 Impact Factor
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    • "Self-starvation and weight loss following from increased running by rats and mice submitted to a restricted feeding schedule in the Activity Based Anorexia model (ABA) [20], [21], [22], [23] revealed a striking parallelism with the symptoms of AN. Besides its interpretation as a form of foraging behavior or its rewarding properties through the activation of dopaminergic reinforcing pathways [5], excessive activity in semi-starved rats has been associated with low levels of the fat-derived hormone leptin [24], association that has also been reported for AN patients [25], [26]. Leptin treatment has been quite effective in suppressing semi-starvation-induced hyperactivity in a modified ABA procedure [27]. "
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    ABSTRACT: Excessive physical activity is a common feature in Anorexia Nervosa (AN) that interferes with the recovery process. Animal models have demonstrated that ambient temperature modulates physical activity in semi-starved animals. The aim of the present study was to assess the effect of ambient temperature on physical activity in AN patients in the acute phase of the illness. Thirty-seven patients with AN wore an accelerometer to measure physical activity within the first week of contacting a specialized eating disorder center. Standardized measures of anxiety, depression and eating disorder psychopathology were assessed. Corresponding daily values for ambient temperature were obtained from local meteorological stations. Ambient temperature was negatively correlated with physical activity (p = -.405) and was the only variable that accounted for a significant portion of the variance in physical activity (p = .034). Consistent with recent research with an analogous animal model of the disorder, our findings suggest that ambient temperature is a critical factor contributing to the expression of excessive physical activity levels in AN. Keeping patients warm may prove to be a beneficial treatment option for this symptom.
    PLoS ONE 07/2012; 7(7):e41851. DOI:10.1371/journal.pone.0041851 · 3.23 Impact Factor
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