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

Abstract

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.

• Authors: Veronica Prpic, Patricia M Watson, Isabell C Frampton, Mark A Sabol, G Eric Jezek, Thomas W Gettys
• Journal: Endocrinology (Endocrinology) Vol. 144 Issue 4 Pg. 1155-63 (Apr 2003) ISSN: 0013-7227 [Print] United States
• PMID: 12639896 (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
• Ucp1 protein, mouse
• Uncoupling Protein 1

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)
• Uncoupling Protein 1