Endospanin 1 silencing in the hypothalamic arcuate nucleus contributes to sustained weight loss of high fat diet obese mice
| Autor: | Ralf Jockers, Virginie Vauthier, Julie Dam, Patty Chen, M Pagnon, Clara Roujeau, T D Swartz, Chamsy Sarkis, Jacques Mallet |
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| Rok vydání: | 2014 |
| Předmět: |
Leptin
Male STAT3 Transcription Factor medicine.medical_specialty Mice Obese Biology Diet High-Fat Mice Weight loss Internal medicine Weight Loss Genetics medicine Animals Obesity Receptor Molecular Biology Arc (protein) Leptin receptor digestive oral and skin physiology Arcuate Nucleus of Hypothalamus Intracellular Signaling Peptides and Proteins medicine.disease Lipids Mice Inbred C57BL Endocrinology Gene Expression Regulation Hypothalamus Molecular Medicine medicine.symptom Steatosis Carrier Proteins |
| Zdroj: | Gene Therapy. 21:638-644 |
| ISSN: | 1476-5462 0969-7128 |
| Popis: | Leptin targets specific receptors (OB-R) expressed in the hypothalamus to regulate energy balance. Leptin decreases food intake in normal weight individuals, but this effect is blunted in obese subjects who are characterized by a state of leptin resistance. The prevention of leptin resistance is one of the major goals of obesity research. Recently, we identified endospanin 1 as a negative regulator of OB-R, which by interacting with OB-R retains the receptor inside the cell. We show here that in obese mice endospanin 1 is upregulated in the hypothalamic arcuate nucleus (ARC), the major brain structure involved in body weight regulation, suggesting that endospanin 1 is implicated in obesity development and/or the installation of leptin resistance. In contrast, silencing of endospanin 1 with lentiviral vectors in the ARC of obese mice fully restores leptin responsiveness when combined with a switch to ad libitum fed chow diet. The recovery of central leptin sensitivity is accompanied by sustained body weight loss and amelioration of blood lipid parameters and steatosis. Collectively, our results define endospanin 1 as a novel therapeutic target against obesity. |
| Databáze: | OpenAIRE |
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