Watson P M, Commins S P, Beiler R J, Hatcher H C, Gettys T W
Departments of Medicine and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Am J Physiol Endocrinol Metab. 2000 Aug;279(2):E356-65. doi: 10.1152/ajpendo.2000.279.2.E356.
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.
将抗肥胖（A/J）和易肥胖（C57BL/6J）小鼠断奶后分别给予低脂（LF）或高脂（HF）饮食，并在2周、10周和16周后进行研究。在整个研究过程中，尽管A/J小鼠和C57BL/6J小鼠摄入的食物量相同，但食用高脂饮食的A/J小鼠体脂沉积较少，体重增加也少于C57BL/6J小鼠。高脂饮食使两个品系小鼠的白色脂肪组织（WAT）中瘦素mRNA水平均升高，但A/J小鼠的升高水平显著高于C57BL/6J小鼠。高脂饮食分别诱导A/J小鼠棕色脂肪组织（BAT）和白色脂肪组织中的解偶联蛋白1（UCP1）和UCP2 mRNA表达增加，但C57BL/6J小鼠未出现这种情况。与C57BL/6J小鼠相比，A/J小鼠腹膜后白色脂肪组织中的UCP1 mRNA水平也显著更高。A/J小鼠抵抗饮食诱导肥胖的能力与脂肪组织中瘦素、UCP1和UCP2表达的品系特异性增加有关。这些发现表明，高脂饮食不会损害A/J小鼠中瘦素依赖的脂肪细胞基因表达调控，并提示维持瘦素反应性赋予了对饮食诱导肥胖的抵抗力。
