دورية أكاديمية

Leptin Regulates Nutrient Reward via Galanin and Orexin Neurons

التفاصيل البيبلوغرافية
العنوان: Leptin Regulates Nutrient Reward via Galanin and Orexin Neurons
المؤلفون: Laque, Amanda
المصدر: LSU Doctoral Dissertations
بيانات النشر: LSU Digital Commons
سنة النشر: 2014
المجموعة: LSU Digital Commons (Louisiana State University)
مصطلحات موضوعية: reward, orexin, galanin, leptin
الوصف: Obesity has become a widespread concern to human health largely over the past three decades. It is thought that obesity is associated with the over consumption of calorically dense diets. The rewarding value of food is mediated through the mesolimbic dopamine system, though is less understood how appetitive control circuits relay information to existing reward circuitry. The adiposity signaling hormone, leptin, is a critical mediator of food intake and fat storage. Leptin signaling, via the long form of the leptin receptor (LepRb), is predominantly carried out within the hypothalamus. Leptin action specific to the lateral hypothalamus area (LHA) modulates reward function via direct and indirect inhibition of reward circuitry. Here, I have identified a novel leptin receptor population within the LHA that co-expresses the inhibitory neuropeptide galanin (termed Gal-LepRb neurons). To investigate the physiological function of leptin through Gal-LepRb neurons, we selectively deleted LepRb in galanin neurons (referred to as Gal-LepRbKO mice). In a two-bottle-choice paradigm, I assessed nutrient selection for isocaloric lipid and sucrose solutions. Interestingly, Gal-LepRbKO mice demonstrated a significant preference for the sucrose solution and decreased lipid intake compared to controls. Moreover, Gal-LepRbKO mice displayed stronger motivation to work for a sucrose treat. My data further indicate that Gal-LepRb neurons are inhibitory acting neurons that are stimulated by leptin. Gal-LepRb neurons strongly innervate local orexin neurons and noradrenergic neurons in the locus coeruleus (LC). Intriguingly, orexin neurons also strongly innervate the LC, and activation of orexin neurons correlates with motivational and food-seeking behaviors. My data also show that orexin neurons express the Gi-coupled GPCR galanin 1-receptor (GalR1), validating the cellular ability of orexin neurons to respond to galanin. In summary, we have characterized a novel population of LHA LepRb neurons and propose that leptin-mediated ...
نوع الوثيقة: text
وصف الملف: application/pdf
اللغة: unknown
العلاقة: https://digitalcommons.lsu.edu/gradschool_dissertations/3829Test; https://digitalcommons.lsu.edu/context/gradschool_dissertations/article/4828/viewcontent/Laquediss.pdfTest
DOI: 10.31390/gradschool_dissertations.3829
الإتاحة: https://doi.org/10.31390/gradschool_dissertations.3829Test
https://digitalcommons.lsu.edu/gradschool_dissertations/3829Test
https://digitalcommons.lsu.edu/context/gradschool_dissertations/article/4828/viewcontent/Laquediss.pdfTest
رقم الانضمام: edsbas.5C72B322
قاعدة البيانات: BASE
الوصف
DOI:10.31390/gradschool_dissertations.3829