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. Des pite consuming the same amount of food, A/J mice on the HF diet deposited l ess 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 b oth strains on the HF diet but to significantly higher levels in A/J compar ed with C57BL/6J mice. Uncoupling protein 1 (UCP1) and UCP2 mRNA were induc ed by the HF diet in brown adipose tissue (BAT) and WAT of A/J mice, respec tively, but not in C57BL/6J mice. UCP1 mRNA was also significantly higher i n 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 findin gs indicate that the HF diet does not compromise leptin-dependent regulatio n of adipocyte gene expression in A/J mice and suggest that maintenance of leptin responsiveness confers resistance to diet-induced obesity.