Ohara M, Tsutsumi K, Ohsawa N
Nutrition Research Institute, Otsuka Pharmaceutical, Naruto, Tokushima, Japan.
Metabolism. 1998 Jan;47(1):101-5. doi: 10.1016/s0026-0495(98)90201-3.
The Leydig cell tumor has been reported to produce tumor necrosis factor (TNF) and induce cachexia in rats. TNF is thought to reduce lipoprotein lipase (LPL) activity, decrease fat deposits, induce emaciation, and worsen cachexia. Therefore, we thought emaciation might be prevented and thus cachexia improved by increasing LPL activity. We administered NO-1886, a lipoprotein lipase activator, to rats bearing Leydig cell tumor and observed its effect on improving the cachexia induced by the tumor. In Leydig cell tumor-bearing rats, the emaciation progressed after tumor inoculation and the general condition worsened daily. Plasma levels of total protein, albumin, and glucose, which are biological parameters of malnutrition, were found to decrease soon after tumor inoculation in tumor-bearing rats. In contrast, rats given NO-1886 showed less malnutrition than tumor-bearing rats. LPL activity of rat adipose tissue was decreased, the weight of adipose tissue was decreased, carcass weight was reduced, and food consumption was decreased after Leydig cell tumor inoculation. NO-1886 increased adipose tissue LPL activity and suppressed the decrease in the weight of adipose tissue, carcass weight, and food consumption due to cachexia without influencing tumor growth. The present results suggest that the novel compound NO-1886 may suppress carcass weight loss in rats bearing Leydig cell tumor by suppressing the decrease in food consumption and LPL activity.
据报道，睾丸间质细胞瘤可产生肿瘤坏死因子（TNF）并在大鼠中诱发恶病质。TNF被认为会降低脂蛋白脂肪酶（LPL）的活性，减少脂肪沉积，导致消瘦，并使恶病质恶化。因此，我们认为通过提高LPL活性可能预防消瘦，从而改善恶病质。我们给患有睾丸间质细胞瘤的大鼠施用脂蛋白脂肪酶激活剂NO-1886，并观察其对改善肿瘤诱发的恶病质的作用。在患有睾丸间质细胞瘤的大鼠中，接种肿瘤后消瘦情况加重，总体状况每日恶化。在接种肿瘤的大鼠中，发现肿瘤接种后不久，作为营养不良生物学指标的血浆总蛋白、白蛋白和葡萄糖水平就会下降。相比之下，给予NO-1886的大鼠比患有肿瘤的大鼠营养不良程度轻。接种睾丸间质细胞瘤后，大鼠脂肪组织的LPL活性降低，脂肪组织重量减轻，胴体重量减少，食物消耗量下降。NO-1886增加了脂肪组织的LPL活性，并抑制了由于恶病质导致的脂肪组织重量、胴体重量和食物消耗量的下降，而不影响肿瘤生长。目前的结果表明，新型化合物NO-1886可能通过抑制食物消耗量和LPL活性的下降来抑制患有睾丸间质细胞瘤大鼠的胴体重量减轻。
