Patterson Christa M, Bouret Sebastien G, Dunn-Meynell Ambrose A, Levin Barry E
Neurology Service (127C VA Medical Center, 385 Tremont Ave., E. Orange, NJ 07018-1095, USA.
Am J Physiol Regul Integr Comp Physiol. 2009 Mar;296(3):R537-48. doi: 10.1152/ajpregu.90859.2008. Epub 2009 Jan 21.
In rats selectively bred to develop diet-induced obesity (DIO) 3 wk of postweaning exercise reduces weight and adipose regain for 10 wk after exercise cessation, despite intake of 31% fat high-energy (HE) diet. To test the hypothesis that this effect is due to increased central leptin sensitivity, 4-wk-old DIO rats were fed the HE diet and left sedentary (Sed), exercised for 3 wk, and then remained sedentary for 10 additional weeks (Ex/Sed) or continued exercise for a full 13 wk (Ex). After 3 wk, leptin (5 mg/kg ip) induced a 36% decrease in 24-h food intake in Ex rats, while Sed rats had no change in 24-h intake. Ex rats also had 23% more leptin-induced phospho-STAT3 (pSTAT3)-expressing neurons in the arcuate nucleus (ARC) and 95% and 68% higher (125)I-labeled leptin receptor binding in the ventromedial and dorsomedial nuclei than did Sed rats, respectively. At 7 wk after onset, leptin decreased 24-h intake by 20% in Ex and 24% in Ex/Sed rats without altering Sed intake. After a total of 13 wk, compared with Sed rats, Ex and Ex/Sed rats had 58% and 38% less fat, respectively, but leptin failed to decrease food intake in any group. Nevertheless, Ex, but not Ex/Sed rats, still had 32% more ARC leptin-induced pSTAT3-expressing neurons than Sed rats. These data suggest that brief postweaning exercise in DIO rats that are inherently leptin resistant causes a sustained resistance to obesity on HE diet, which is, in part, due to increased central leptin sensitivity.
在经选择性培育以发展为饮食诱导性肥胖（DIO）的大鼠中，断奶后3周的运动可减轻体重，并在运动停止后10周内防止体重和脂肪再度增加，尽管其摄入的是31%脂肪的高能（HE）饮食。为了验证这种效应是由于中枢性瘦素敏感性增加这一假说，给4周龄的DIO大鼠喂食HE饮食，并使其保持久坐不动（Sed），运动3周，然后再保持久坐不动10周（Ex/Sed），或持续运动13周（Ex）。3周后，瘦素（5毫克/千克，腹腔注射）使Ex组大鼠24小时食物摄入量减少了36%，而Sed组大鼠24小时摄入量没有变化。Ex组大鼠在弓状核（ARC）中由瘦素诱导的磷酸化信号转导和转录激活因子3（pSTAT3）表达神经元也比Sed组大鼠多23%，并且在腹内侧核和背内侧核中，（125）I标记的瘦素受体结合量分别比Sed组大鼠高95%和68%。在开始运动7周后，瘦素使Ex组大鼠24小时摄入量减少了20%，使Ex/Sed组大鼠减少了24%，而未改变Sed组大鼠的摄入量。总共13周后，与Sed组大鼠相比，Ex组和Ex/Sed组大鼠的脂肪分别减少了58%和38%，但瘦素未能使任何一组的食物摄入量减少。然而，Ex组大鼠（而非Ex/Sed组大鼠）在ARC中由瘦素诱导的pSTAT3表达神经元仍比Sed组大鼠多32%。这些数据表明，在天生对瘦素抵抗的DIO大鼠中进行短暂的断奶后运动，可使其在HE饮食上对肥胖产生持续的抵抗力，这部分是由于中枢性瘦素敏感性增加所致。
