title: Lentiviral vector-mediated knockdown of Lrb in the arcuate nucleus promotes diet-induced obesity in rats.
abstract: Obesity is currently a worldwide pandemic. Leptin resistance is a main mechanism of obese human and rodents. The downregulation of the long form of the leptin receptor (Lrb) was involved in leptin resistance in diet-induced obese rats. In the studies, we investigated whether arcuate nucleus (ARC) silencing of Lrb would promote diet-induced obesity in rats. Lentiviral vectors expressing Lrb-shRNA were administered to 5-week-old male rats by ARC injection. Following viral delivery, the rats were provided with a high-fat diet (HFD) or a chow diet (CD). After 8 weeks of the diet, serum leptin, and insulin concentrations were measured by RIA, gene expression of Lrb in the ARC was detected by a real-time RT-PCR, and leptin signaling was examined by western blot. The Lrb-shRNA knocked down the expression of Lrb mRNA in infected regions by 54% for the HFD rats and 47% for the CD rats respectively. The Lrb knockdown reduced Stats3 activation and increased expression of Npy mRNA. The rats with reduced Lrb in the ARC showed a significant increase in energy intake and body weight (BW) again when fed with a HFD. By contrast, there were no effects of Lrb reduction on energy intake or BW when rats maintained on a low-fat chow. Our results provide evidence that Lrb knockdown selectively in the ARC promotes diet-induced obesity and associated metabolic complications in rats.
authors.affiliation: Department of Pediatrics, The Second Affiliated Hospital, Dalian Medical University, Shahekou District, Dalian 116027, China.
authors.forename: J
authors.initials: J
authors.lastname: Bian
authors.forename: X M
authors.initials: XM
authors.lastname: Bai
authors.forename: Y L
authors.initials: YL
authors.lastname: Zhao
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Liu
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D020738:Leptin / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D054411:Receptors, Leptin / Q000235:genetics*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D034741:RNA, Small Interfering; D054411:Receptors, Leptin; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: leptin; metabolism; obesity; receptors