MacLean Paul S, Higgins Janine A, Jackman Matthew R, Johnson Ginger C, Fleming-Elder Brooke K, Wyatt Holly R, Melanson Edward L, Hill James O
Center for Human Nutrition, Department of Medicine, University of Colorado at Denver and Health Sciences Center, PO Box 6511, F-8305, Aurora, CO 80045, USA.
Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1577-88. doi: 10.1152/ajpregu.00810.2005. Epub 2006 Feb 2.
Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.
体重减轻后体重反弹是长期减重的最主要障碍。我们建立了一种啮齿动物模型来模拟体重减轻后的反弹过程，并采用前瞻性和横断面分析来描述对体重减轻的代偿性适应，这些适应可能导致体重反弹倾向。给肥胖大鼠喂食能量受限（50 - 60%千卡）的低脂饮食，使其体重减轻14%。通过有限供应低脂饮食，将减轻的体重维持长达16周。然后去除摄入限制，对大鼠进行56天的跟踪观察，直至它们恢复到肥胖状态。长期体重减轻伴随着：1）因进食驱动力增加和能量消耗减少导致的持续能量缺口；2）更高的反弹热量效率，这可能与复发过程早期脂质利用受抑制有关；3）脂肪组织中脂质优先积累并伴有脂肪细胞增生；4）体液肥胖信号低估外周肥胖水平，并可能影响控制能量平衡的神经通路。综上所述，在这种啮齿动物模型中，长期体重减轻伴随着外周一系列相互关联的代偿性调整，这些调整共同作用以促进快速且有效的体重反弹。在控制体重的稳态反馈系统背景下讨论了这些对体重减轻的代谢调整。
