Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice
Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice
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DOI：
10.4161/15384047.2014.987075
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发表时间：
2015-06-01
影响因子：
3.6
通讯作者：
Belury, Martha A.
中科院分区：
文献类型：
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作者：
Kliewer, Kara L.;Ke, Jia-Yu;Belury, Martha A.
癌症恶病质是一种进行性代谢紊乱，导致脂肪组织和骨骼肌的消耗。越来越多的文献表明，在恶病质中维持脂肪组织质量可能改善生活质量和生存结果。然而，对恶病质中脂质代谢的研究通常集中在疾病的晚期，此时已经发生了严重的脂肪组织损失。在这里，我们研究了结肠-26小鼠恶病质模型中，在严重脂肪减少之前，脂肪、肝脏和肌肉组织在早期恶病质中的脂质代谢。在本研究中，早期恶病质小鼠的白色脂肪组织质量适度减少（34-42%），体重减轻不到初始体重的10%。在恶质小鼠的白色脂肪库中，我们发现了蛋白激酶A激活的脂肪分解增强的证据，这与总能量消耗增加和棕色（但不是白色）脂肪组织产热和急性期反应标志物的表达增加相一致。在早期恶病质中，肝脏和肌肉的总脂质没有变化，而脂肪氧化标志物增加。许多这些初始代谢反应与恶病质后期脂质代谢的报道形成对比。我们的观察结果表明，在恶病质中保持脂肪量的干预研究应该针对恶病质的阶段进行调整。我们的观察结果还强调，有必要研究恶病质阶段和动物模型对癌症恶病质中脂质代谢改变的贡献，并确定那些最接近模拟人类状况的研究。
Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.