Open AccessAblation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility
Author(s) -
Qi Wu,
Benjamin B. Whiddon,
Richard D. Palmiter
Publication year - 2012
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1120501109
Subject(s) - leptin , medicine , endocrinology , melanin concentrating hormone , biology , hormone , fertility , body weight , obesity , receptor , population , environmental health , neuropeptide
Leptin-deficient (Lepob/ob ) mice are obese, diabetic, and infertile. Ablation of neurons that make agouti-related protein (AgRP) in moderately obese adultLepob/ob mice caused severe anorexia. The mice stopped eating for 2 wk and then gradually recovered. Their body weight fell to within a normal range for WT mice, at which point food intake and glucose tolerance were restored to that of WT mice. Remarkably, both male and femaleLepob/ob mice became fertile. Ablation of neurons that express melanin-concentrating hormone (MCH) in adultLepob/ob mice had no effect on food intake, body weight, or fertility, but resulted in improved glucose tolerance. We conclude that AgRP-expressing neurons play a critical role in mediating the metabolic syndrome and infertility ofLepob/ob mice, whereas MCH-expressing neurons have only a minor role.