Nutritional Regulation of Hypothalamic Leptin Receptor Gene Expression is Defective in Diet-Induced Obesity
| Autor: | A. Sahu, R. M. O'Doherty, L. Nguyen |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Messenger RNA
medicine.medical_specialty Leptin receptor Endocrine and Autonomic Systems Endocrinology Diabetes and Metabolism Leptin Biology medicine.disease Obesity Cellular and Molecular Neuroscience Endocrinology Cerebrospinal fluid Hypothalamus Internal medicine Gene expression medicine Receptor hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Neuroendocrinology. 14:887-893 |
| ISSN: | 0953-8194 |
| DOI: | 10.1046/j.1365-2826.2002.00856.x |
| Popis: | Leptin action in the hypothalamus plays a critical role in maintaining normal food intake and body weight. Hyperleptinaemia is associated with obesity in humans and animal models, suggesting a state of leptin resistance. Although the mechanism of leptin resistance is not clearly understood, alterations in leptin receptor (Ob-R) gene expression have been proposed as a potential mechanism mediating modifications in leptin action in obesity and during changes in nutritional status (fed/fasted). The current study examined the effects of diet-induced obesity (DIO) made by feeding rats a high fat diet for 9 weeks, and nutritional status on levels of long form (Ob-Rb) and total (Ob-Rtot) Ob-R mRNA expression in the hypothalamus. In the fed state, hypothalamic Ob-Rb mRNA and Ob-Rtot mRNA levels were similar in DIO and control standard chow fed rats (SC) despite hyperleptinaemia in DIO rats. However, although an overnight fast moderately increased hypothalamic Ob-Rb mRNA levels in SC rats, fasting did not increase Ob-Rb mRNA levels in DIO rats. To address the possibility that elevated leptin concentration in DIO rats may mediate an alteration in OB-R mRNA levels, we examined the effects of adenovirus-mediated hyperleptinaemia on Ob-R gene expression in SC rats. Despite substantially elevated plasma and cerebrospinal fluid concentrations of leptin, hypothalamic Ob-R mRNA levels were similar in both groups. In conclusion, the current study demonstrates that DIO is associated with a loss of nutritional regulation of hypothalamic Ob-R mRNA levels, and that hyperleptinaemia is not sufficient to alter Ob-R mRNA expression. |
| Databáze: | OpenAIRE |
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