Agouti-related protein-deficient mice display an age-related lean phenotype

Cell Metab. 2005 Dec;2(6):421-7. doi: 10.1016/j.cmet.2005.11.004.


Endogenous modulators of the central melanocortin system, such as the agouti-related protein (AgRP), should hold a pivotal position in the regulation of energy intake and expenditure. Despite this, AgRP-deficient mice were recently reported to exhibit normal food intake, body weight gain, and energy expenditure. Here we demonstrate that 2- to 3-month-old Agrp null mice do in fact exhibit subtle changes in response to feeding challenges (fasting and MCR agonists) but, of more significance and magnitude, exhibit reduced body weight and adiposity after 6 months of age. This age-dependent lean phenotype is correlated with increased metabolic rate, body temperature, and locomotor activity and increased circulating thyroid hormone (T4 and T3) and BAT UCP-1 expression. These results provide further proof of the importance of the AgRP neuronal system in the regulation of energy homeostasis.

MeSH terms

  • Adipose Tissue / metabolism
  • Adrenal Glands / metabolism
  • Aging
  • Agouti-Related Protein
  • Animals
  • Body Composition
  • Body Temperature
  • Body Weight
  • Brain / metabolism
  • Calorimetry
  • Feeding Behavior
  • Gene Expression Regulation
  • Genetic Vectors
  • Intercellular Signaling Peptides and Proteins
  • Lac Operon
  • Mice
  • Mice, Transgenic
  • Models, Genetic
  • Neurons / metabolism
  • Phenotype
  • Proteins / genetics*
  • Proteins / physiology*
  • Thyroid Hormones / metabolism
  • Time Factors
  • beta-Galactosidase / metabolism


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • Thyroid Hormones
  • beta-Galactosidase