The effects of leptin deficiency on cold-induced energy expenditure

At 24°C Lep-/- mice are hyperphagic compared to the Lep+/+ mice. Reducing the ambient temperature from 24 to 6°C (3°C per day) was accompanied by a graded parallel increase in food intake in both control and Lep-/- mice. The rate of increase in food intake per degree Celsius reduction in ambient temperature by the control mice and Lep-/- mice was essentially indistinguishable. Since the body composition of Lep+/+ and Lep-/- mice was unchanged during cold exposure, thermogenesis is fueled solely by food intake. Accordingly, we predicted that the same changes in gene expression associated with the central regulation of thermogenesis by the hypothalamus must occur in both Lep+/+ and Lep-/- mice during the transition from 24 to 6°C. Microarray analysis of gene expression was performed on hypothalamic tissue dissected from Lep-/- and Lep+/+ mice kept at different temperature conditions, that is, in mice maintained at 24°C and in mice in which the ambient temperature had been reduced to 6°C over 6 days.在24℃环境下，瘦素缺失（Lep-/-）小鼠相较于野生型（Lep+/+）小鼠表现出食欲亢进症状。将环境温度以每日3℃的速率从24℃逐步降至6℃的过程中，对照组（Lep+/+）与瘦素缺失（Lep-/-）小鼠的进食量均呈现分级式平行上升趋势。对照组与瘦素缺失小鼠每降低1℃环境温度所对应的进食量增长速率基本无显著差异。由于冷暴露过程中野生型与瘦素缺失小鼠的身体成分未发生改变，因此机体产热仅由进食提供能量支撑。据此我们推测，在环境温度从24℃过渡至6℃的过程中，下丘脑对产热进行中枢调控所关联的基因表达变化，在野生型与瘦素缺失小鼠体内均会发生。研究人员对不同温度条件下饲养的瘦素缺失与野生型小鼠的解剖下丘脑组织开展了基因表达微阵列（Microarray）分析，受试小鼠分为两类：一类持续处于24℃环境，另一类经6天逐步降温至6℃环境。