Lipid Science & Technology

Biography

Biography: Allison W Xu

Abstract

    Obesity     develops with chronic consumption of palatable energy-dense diets, and also with increasing age. With persistent positive energy balance, the increase in body weight is accompanied by a steady rise in circu lating    leptin    levels , indicating the progressive development of counter regulatory mechanisms to antagonize leptin's anorexigenic effects.    Hypothalamic    neurons co-expressing agouti-related peptide (AgRP) and   neuropeptide   Y are direct leptin targets. We have recently shown that AgRP neurons are the predominant cell type situated outside the blood-bra in barrier in the mediobasal   hypot halamus  . AgRP neurons are able to sense slight changes in plasma metabolic signals, such as leptin, but they also more quickly develop cellular leptin resistance in contr ast to  proopiomelanocortin  (POMC)  and other hypothalamic neurons that remain leptin-sensitive. AgRP neurons also display age-dependent increase in innervation onto their target neurons, and this process is accelerated by chronic  high-fat feeding. Our studies suggest that AgRP neurons are critical sensors for peripheral metabolic hormones and that they play a dynamic role in metabolic fine tuning in response to acute changes in  nutritional  status. Our studies also suggest that these neurons, with their unique anatomical relationship with the blood-brain barrier, could serve as important targets for therapeutic intervention for the treatme  nt of metabolic disorders