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Evidence for the Existence of Distinct Central Appetite, Energy Expenditure, and Ghrelin Stimulation Pathways as Revealed by Hypothalamic Site-Specific Leptin Gene Therapy
Distinct brain pathways control appetite, energy use, and hunger hormone response shown by targeted leptin gene therapy
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Abstract
Leptin transgene expression in the paraventricular nucleus and ventromedial nucleus led to 26-29% body weight reduction in female rats.
- Daily food intake decreased by 18-20% with leptin expression in the ventromedial nucleus and paraventricular nucleus.
- Leptin expression resulted in drastic reductions in serum leptin (81-97%) and insulin (92-93%), along with decreased free fatty acids (35-36%).
- In the arcuate nucleus, leptin expression decreased body weight gain by 21% and food intake by 11%, with metabolic hormones suppressed similarly.
- Leptin expression in the medial preoptic area reduced body weight and metabolic hormones without affecting food intake.
- All hypothalamic sites of leptin expression increased serum ghrelin and thermogenic energy expenditure, indicated by raised uncoupling protein-1 mRNA in brown adipose tissue.
- Proopiomelanocortin gene expression was up-regulated by leptin in all sites, while neuropeptide Y expression was suppressed only in the arcuate nucleus.
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