Leptin actions on food intake and body temperature are mediated by IL-1
| Autor: | Jason D. Gardner, Nancy J. Rothwell, Andrew S. I. Loudon, Giamal N. Luheshi, David Rushforth |
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| Rok vydání: | 1999 |
| Předmět: |
Leptin
Male medicine.medical_specialty medicine.drug_class Sialoglycoproteins media_common.quotation_subject Pharmacology Body Temperature Proinflammatory cytokine Rats Sprague-Dawley Eating Mice Internal medicine medicine Animals Receptor media_common Multidisciplinary Leptin receptor biology Chemistry digestive oral and skin physiology Proteins Appetite Biological Sciences Receptor antagonist Rats Rats Zucker Interleukin 1 Receptor Antagonist Protein Endocrinology Hypothalamus Antirheumatic Agents biology.protein Cyclooxygenase hormones hormone substitutes and hormone antagonists Interleukin-1 |
| Zdroj: | Proceedings of the National Academy of Sciences. 96:7047-7052 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.96.12.7047 |
| Popis: | Leptin regulates energy balance through its actions in the brain on appetite and energy expenditure and also shares properties with cytokines such as IL-1. We report here that leptin, injected into rats intracerebroventricularly or peripherally, induces significant dose-dependent increases in core body temperature as well as suppression of appetite. Leptin failed to affect food intake or body temperature in obese (fa/fa) Zucker rats, which posses a defective leptin receptor. Furthermore, injection of leptin increased levels of the proinflammatory cytokine IL-1β in the hypothalamus of normal Sprague–Dawley rats. Central injection of IL-1 receptor antagonist (IL-1ra) inhibited the suppression of food intake caused by central or peripheral injection of leptin (60 and 84%, respectively) and abolished the leptin-induced increase in body temperature in both cases. Mice lacking (gene knockout) the main IL-1 receptor (80 kDa, R1) responsible for IL-1 actions showed no reduction in food intake in response to leptin. These data indicate that leptin actions in the brain depend on IL-1, and we show further that the effect of leptin on fever, but not food intake, is abolished by a cyclooxygenase inhibitor. Thus, we propose that in addition to its role in body weight regulation, leptin may mediate neuroimmune responses via actions in the brain dependent on release of IL-1 and prostaglandins. |
| Databáze: | OpenAIRE |
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