Ablation of neurons expressing agouti-related protein, but not melanin concentrating hormone, in leptin-deficient mice restores metabolic functions and fertility
Abstract
Leptin-deficient (Lepob/ob) mice are obese, diabetic, and infertile. Ablation of neurons that make agouti-related protein (AgRP) in moderately obese adult Lepob/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 female Lepob/ob mice became fertile. Ablation of neurons that express melanin-concentrating hormone (MCH) in adult Lepob/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 of Lepob/ob mice, whereas MCH-expressing neurons have only a minor role.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- February 2012
- DOI:
- 10.1073/pnas.1120501109
- Bibcode:
- 2012PNAS..109.3155W