Differential mechanisms and development of leptin resistance in A/J versus C57BL/6J mice during diet-induced obesity

Endocrinology. 2003 Apr;144(4):1155-63. doi: 10.1210/en.2002-220835.


Changes in the biological efficacy of leptin were evaluated in obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice at weaning and after consuming a high-fat (HF) diet for 4 and 8 wk. There was no evidence of leptin resistance in either strain at the start of the study, but after 4 and 8 wk on the HF diet, C57BL/6J mice became unresponsive to ip leptin. C57BL/6J mice responded to intracerebroventricular leptin at these time points but developed peripheral resistance to sympathetic stimulation of retroperitoneal white adipose tissue. In contrast, intracerebroventricular leptin was fully effective in A/J mice, reproducing the complete profile of responses observed in weanling mice. A/J mice were also partially responsive to ip leptin at both time points, increasing uncoupling protein 1 mRNA expression in brown adipose tissue and decreasing leptin mRNA in white adipose tissue. The findings indicate that retention of leptin responsiveness is an important component of the ability of A/J mice to mount a robust adaptive thermogenic response and resist diet-induced obesity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Carrier Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dietary Fats / pharmacology*
  • Energy Intake
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Ion Channels
  • Leptin / metabolism*
  • Leptin / pharmacology
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mitochondrial Proteins
  • Obesity / metabolism*
  • STAT3 Transcription Factor
  • Species Specificity
  • Trans-Activators / metabolism
  • Uncoupling Protein 1


  • Carrier Proteins
  • DNA-Binding Proteins
  • Dietary Fats
  • Ion Channels
  • Leptin
  • Membrane Proteins
  • Mitochondrial Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Ucp1 protein, mouse
  • Uncoupling Protein 1