AgRP Neurons Regulate Bone Mass

Cell Rep. 2015 Oct 6;13(1):8-14. doi: 10.1016/j.celrep.2015.08.070. Epub 2015 Sep 24.

Abstract

The hypothalamus has been implicated in skeletal metabolism. Whether hunger-promoting neurons of the arcuate nucleus impact the bone is not known. We generated multiple lines of mice to affect AgRP neuronal circuit integrity. We found that mice with Ucp2 gene deletion, in which AgRP neuronal function was impaired, were osteopenic. This phenotype was rescued by cell-selective reactivation of Ucp2 in AgRP neurons. When the AgRP circuitry was impaired by early postnatal deletion of AgRP neurons or by cell autonomous deletion of Sirt1 (AgRP-Sirt1(-/-)), mice also developed reduced bone mass. No impact of leptin receptor deletion in AgRP neurons was found on bone homeostasis. Suppression of sympathetic tone in AgRP-Sirt1(-/-) mice reversed osteopenia in transgenic animals. Taken together, these observations establish a significant regulatory role for AgRP neurons in skeletal bone metabolism independent of leptin action.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti-Related Protein / deficiency
  • Agouti-Related Protein / genetics*
  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Arcuate Nucleus of Hypothalamus / pathology
  • Bone Density / drug effects*
  • Bone Diseases, Metabolic / genetics
  • Bone Diseases, Metabolic / metabolism*
  • Bone Diseases, Metabolic / pathology
  • Femur / drug effects
  • Femur / metabolism*
  • Femur / pathology
  • Gene Expression Regulation
  • Homeostasis
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Hypothalamus / pathology
  • Ion Channels / deficiency
  • Ion Channels / genetics
  • Leptin / genetics
  • Leptin / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / deficiency
  • Mitochondrial Proteins / genetics
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Norepinephrine / metabolism
  • Phenotype
  • Propranolol / pharmacology*
  • Receptors, Adrenergic, beta / genetics
  • Receptors, Adrenergic, beta / metabolism
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism
  • Signal Transduction
  • Sirtuin 1 / deficiency
  • Sirtuin 1 / genetics
  • Tibia / drug effects
  • Tibia / metabolism*
  • Tibia / pathology
  • Uncoupling Protein 2

Substances

  • Agouti-Related Protein
  • Agrp protein, mouse
  • Ion Channels
  • Leptin
  • Mitochondrial Proteins
  • Receptors, Adrenergic, beta
  • Receptors, Leptin
  • Ucp2 protein, mouse
  • Uncoupling Protein 2
  • Propranolol
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Norepinephrine