Differential mechanisms and development of leptin resistance in A/J versus C57BL/6J mice during diet-induced obesity.
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.
Prpic
Veronica
V
Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808, USA.
Watson
Patricia M
PM
Frampton
Isabell C
IC
Sabol
Mark A
MA
Jezek
G Eric
GE
Gettys
Thomas W
TW
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D002149:Energy Intake; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D009765:Obesity / Q000378:metabolism*; D050796:STAT3 Transcription Factor; D013045:Species Specificity; D015534:Trans-Activators / Q000378:metabolism; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004041:Dietary Fats; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1