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      Temperature but not leptin prevents semi-starvation induced hyperactivity in rats: implications for anorexia nervosa treatment

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          Abstract

          The hypothesis linking hyperactivity with weight loss associated hypoleptinemia in anorexia nervosa gained momentum after a study showing that leptin suppressed semi-starvation induced hyperactivity in rats. Alternatively, ambient temperature is a key modulating factor of activity in semi-starved rats. The aim of the study is to compare the efficacy of leptin with increased ambient temperature in the prevention of hyperactivity in semi-starved rats. 74 Sprague-Dawley male rats were employed in two experiments with the difference residing in the length of baseline. After an extended (28 days), or shorter (14 days) baseline with free access to food and the running wheel, housed at 21 °C, animals were either ad-lib feed or food restricted (60% of food ingested during previous week) and infused with same amount of leptin at 21 °C, 25 °C, or vehicle at 21 °C, 25 °C and 32 °C for a week. Animals housed at 32 °C significantly reduced wheel running and weight loss during food restriction while animals given leptin did not yield no differences in activity or weight loss. Moreover, unlike animals housed at 32 °C, body temperature of leptin infused animals housed at 21 °C was significantly reduced during food restriction. Furthermore, leptin treated rats without a preceding stable pattern of activity displayed a severe dysregulation of circadian rhythm in activity and a collapse of body temperature. Housing temperature plays a more critical role than leptin in the regulation of semi-starvation induced hyperactivity in rats, which may be of relevance for the management of hyperactivity in anorexia nervosa.

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          Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight.

          After weight loss, total energy expenditure -- in particular, energy expenditure at low levels of physical activity -- is lower than predicted by actual changes in body weight and composition. An important clinical issue is whether this reduction, which predisposes to weight regain, persists over time. We aimed to determine whether this disproportionate reduction in energy expenditure persists in persons who have maintained a body-weight reduction of > or =10% for >1 y. Seven trios of sex- and weight-matched subjects were studied in an in-patient setting while receiving a weight-maintaining liquid formula diet of identical composition. Each trio consisted of a subject at usual weight (Wt(initial)), a subject maintaining a weight reduction of > or =10% after recent (5-8 wk) completion of weight loss (Wt(loss-recent)), and a subject who had maintained a documented reduction in body weight of >10% for >1 y (Wt(loss-sustained)). Twenty-four-hour total energy expenditure (TEE) was assessed by precise titration of fed calories of a liquid formula diet necessary to maintain body weight. Resting energy expenditure (REE) and the thermic effect of feeding (TEF) were measured by indirect calorimetry. Nonresting energy expenditure (NREE) was calculated as NREE = TEE - (REE +TEF). TEE, NREE, and (to a lesser extent) REE were significantly lower in the Wt(loss-sustained) and Wt(loss-recent) groups than in the Wt(initial) group. Differences from the Wt(initial) group in energy expenditure were qualitatively and quantitatively similar after recent and sustained weight loss. Declines in energy expenditure favoring the regain of lost weight persist well beyond the period of dynamic weight loss.
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            Self-starvation of rats living in activity wheels on a restricted feeding schedule.

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              Proopiomelanocortin neurons are direct targets for leptin in the hypothalamus.

              Leptin is a protein product of the obese (ob) gene, which is secreted by adipocytes and functions as a satiety factor to regulate food intake. The expression of the leptin receptor in several hypothalamic nuclei suggests that multiple neuronal subtypes are targets for leptin's action. Products of the proopiomelanocortin (POMC) gene are known to affect feeding behavior, and POMC neurons share a similar distribution with leptin receptor mRNA in the arcuate nucleus. We used double label in situ hybridization and computerized image analysis to test the hypothesis that POMC neurons coexpress the leptin receptor. Quantitative analysis confirmed that POMC neurons in the hypothalamus express leptin receptor mRNA. Based on this observation, we infer that POMC neurons and the products of the POMC gene may be part of the signaling pathway mediating leptin's action on feeding and perhaps other physiological functions.
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                Author and article information

                Contributors
                emilio.gutierrez@usc.es
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                24 March 2020
                24 March 2020
                2020
                : 10
                : 5300
                Affiliations
                [1 ]ISNI 0000000109410645, GRID grid.11794.3a, Department Psicología Clínica y Psicobiología, , Facultad de Psicología, Universidad de Santiago, Campus Vida, ; 15782 Santiago de Compostela, Spain
                [2 ]ISNI 0000000109410645, GRID grid.11794.3a, Unidad Venres Clínicos, Facultad de Psicología, Campus Vida, Universidad de Santiago, ; 15782 Santiago de Compostela, Spain
                [3 ]Lab de Endocrinología Molecular, Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), Complej o Hospitalario de Santiago (CHUS), A Coruña, Spain
                [4 ]ISNI 0000 0000 9314 1427, GRID grid.413448.e, CIBER Fisiopatología Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, ; Madrid, Spain
                [5 ]ISNI 0000000109410645, GRID grid.11794.3a, Department Fisioloxía and Centro de Investigación en Medicina Molecular (CIMUS), Universidade de Santiago de Compostela, Instituto de Investigaciones Sanitarias de Santiago de Compostela (IDIS), ; Santiago de Compostela, 15782 Spain
                Author information
                http://orcid.org/0000-0002-7823-1648
                http://orcid.org/0000-0001-5808-353X
                Article
                62147
                10.1038/s41598-020-62147-z
                7093431
                32210308
                c33570e3-e6c7-4aac-bf66-a425245818c6
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 22 October 2019
                : 3 March 2020
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100004587, Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III);
                Award ID: PI 17/01287
                Award ID: PI 17/01287
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100010801, Xunta de Galicia;
                Award ID: 2015-CP079
                Award ID: 2016-PG068
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100003329, Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness);
                Award ID: RTI2018-101840-B-I00
                Award ID: BFU2015-70454-REDT/Adipoplast
                Award Recipient :
                Funded by: Atresmedia Corporation
                Categories
                Article
                Custom metadata
                © The Author(s) 2020

                Uncategorized
                psychology,malnutrition
                Uncategorized
                psychology, malnutrition

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