| Intranasal Leptin Reduces Appetite and Induces Weight Loss in Rats with Diet-Induced Obesity (DIO). | |
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MedLine Citation:
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PMID: 22128019 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Resistance to brain-mediated effects of leptin is a characteristic feature of obesity, resulting from alterations in leptin receptor signaling in hypothalamic neurons and/or transport across the blood-brain-barrier. We have shown previously, that the latter can be circumvented by intranasal (i.n.) application of leptin in lean rats. This prompted us to test i.n. leptin in animals with diet-induced obesity (DIO) as a basis for future human administration. DIO was induced in male Wistar rats by feeding a cafeteria diet for 25 or 32 wk, respectively. Consecutively, these DIO animals (seven to eight per treatment) and standard diet rats (lean) (14-15 per treatment, matched for age and diet duration) were treated with 0.1, 0.2 mg/kg leptin, or control solution i.n. daily for 4 wk before onset of dark period. Energy intake and body weight were measured daily; blood glucose, serum insulin, and leptin were measured before and after treatment. Expression of hypothalamic neuropeptides was assessed by quantitative real-time PCR. We demonstrate, for the first time, that i.n. leptin reduces appetite and induces weight loss in DIO to the same extent as in lean rats. Our findings are supported accordingly by an altered expression pattern of anorexigenic and orexigenic neuropeptides in the hypothalamus, e.g. proopiomelanocortin, cocaine and amphetamine-related transcript, neuropeptide Y, agouti-related protein. It now appears clear that i.n. leptin is effectively acting in obese animals in the same fashion as in their lean counterparts. These findings now clearly warrant studies in humans and may open new perspectives in the treatment of obesity. |
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Authors:
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Carla Schulz; Kerstin Paulus; Olaf Jöhren; Hendrik Lehnert |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-29 |
Journal Detail:
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Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-30 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Internal Medicine I (C.S., K.P., H.L.), and Department of Experimental and Clinical Pharmacology and Toxicology (O.J.), University of Luebeck, 23538 Luebeck, Germany. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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