Differential regulation of leptin expression and function in A/J vs. C57BL/6J mice during diet-induced obesity.
Obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice were weaned onto low-fat (LF) or high-fat (HF) diets and studied after 2, 10, and 16 wk. Despite consuming the same amount of food, A/J mice on the HF diet deposited less carcass lipid and gained less weight than C57BL/6J mice over the course of the study. Leptin mRNA was increased in white adipose tissue (WAT) in both strains on the HF diet but to significantly higher levels in A/J compared with C57BL/6J mice. Uncoupling protein 1 (UCP1) and UCP2 mRNA were induced by the HF diet in brown adipose tissue (BAT) and WAT of A/J mice, respectively, but not in C57BL/6J mice. UCP1 mRNA was also significantly higher in retroperitoneal WAT of A/J compared with C57BL/6J mice. The ability of A/J mice to resist diet-induced obesity is associated with a strain-specific increase in leptin, UCP1, and UCP2 expression in adipose tissue. The findings indicate that the HF diet does not compromise leptin-dependent regulation of adipocyte gene expression in A/J mice and suggest that maintenance of leptin responsiveness confers resistance to diet-induced obesity.
Departments of Medicine and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
P M
PM
Watson
S P
SP
Commins
R J
RJ
Beiler
H C
HC
Hatcher
T W
TW
Gettys
D000273:Adipose Tissue / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004041:Dietary Fats; D004435:Eating / Q000502:physiology; D002149:Energy Intake / Q000502:physiology; D015870:Gene Expression; D006128:Growth / Q000502:physiology; D007473:Ion Channels; D020738:Leptin / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D004041:Dietary Fats; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3