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

AbstractChanges 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.
AuthorsVeronica Prpic, Patricia M Watson, Isabell C Frampton, Mark A Sabol, G Eric Jezek, Thomas W Gettys (Affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.)
JournalEndocrinology (Endocrinology) Vol. 144 Issue 4 Pg. 1155-63 (Apr 2003) ISSN: 0013-7227 United States
PMID12639896 (Publication Type: Comparative Study, Journal Article, 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.)
Chemical References
  • Carrier Proteins
  • DNA-Binding Proteins
  • Dietary Fats
  • Ion Channels
  • Leptin
  • Membrane Proteins
  • Mitochondrial Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • mitochondrial uncoupling protein
Topics
  • Adipose Tissue (drug effects, metabolism)
  • Animals
  • Carrier Proteins (genetics)
  • DNA-Binding Proteins (metabolism)
  • Dietary Fats (pharmacology)
  • Energy Intake
  • Gene Expression (drug effects, physiology)
  • Hypothalamus (drug effects, metabolism)
  • Ion Channels
  • Leptin (metabolism, pharmacology)
  • Membrane Proteins (genetics)
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mitochondrial Proteins
  • Obesity (metabolism)
  • STAT3 Transcription Factor
  • Species Specificity
  • Trans-Activators (metabolism)