de Fatima Silva Flaviane, Ortiz-Silva Milene, de Souza Galia Winny Beatriz, Cassolla Priscila, Graciano Maria Fernanda Rodrigues, Zaia Cassia Thaïs Bussamra Vieira, Zaia Dimas, Carpinelli Ângelo Rafael, da Silva Francemilson Goulart, de Souza Helenir Medri
Department of Physiological Sciences, State University of Londrina, 86051-990 Londrina, PR, Brazil.
Department of Chemistry, State University of Londrina, 86051-990 Londrina, PR, Brazil.
Life Sci. 2017 Feb 15;171:68-74. doi: 10.1016/j.lfs.2016.12.016. Epub 2016 Dec 26.
The lipogenic effect of pioglitazone (PGZ), an insulin (INS) sensitizer, is well established. However, few studies have evaluated PGZ effects in preventing weight loss in cancer. We investigated PGZ effects, alone or associated with INS, on INS resistance, cachexia and metabolic abnormalities induced by Walker-256 tumor in rats.
PGZ (5.0mg·kg, oral) or PGZ+INS (NPH, 1.0UI·kg, sc), were once-daily administered during 12days, starting on the day inoculation of Walker-256 tumor cells. Rats were separated in small (about 17g) and big (about 30g) tumor-bearing.
Big tumor-bearing rats showed greater cachexia, blood triacylglycerol and free fatty acids and INS resistance. PGZ and PGZ+INS treatments did not change tumor growth and food intake, but reduced several abnormalities such as INS resistance, increased blood free fatty acids, retroperitoneal fat wasting and body weight loss in small tumor-bearing rats. The prevention of retroperitoneal fat wasting did not involve reduction of tumor necrosis factor-α expression increased. In big tumor-bearing rats, PGZ and PGZ+INS treatments reversed the high blood triacylglycerol and free fatty acids levels, but had no effect on other parameters.
PGZ and PGZ+INS improved INS peripheral sensitivity, possibly by decreasing blood free fatty acids, and reduced fat tissue wasting and body weight loss in small tumor-bearing rats. The results suggest clinical benefits of PGZ in preventing INS resistance, adipose tissue wasting and weight loss when the tumor is small, i.e., in less severe cachexia.
胰岛素增敏剂吡格列酮（PGZ）的脂肪生成作用已得到充分证实。然而，很少有研究评估PGZ在预防癌症患者体重减轻方面的作用。我们研究了PGZ单独或与胰岛素（INS）联合使用对Walker-256肿瘤诱导的大鼠胰岛素抵抗、恶病质和代谢异常的影响。
从接种Walker-256肿瘤细胞当天开始，连续12天每天口服一次PGZ（5.0mg·kg）或PGZ+INS（中性鱼精蛋白锌胰岛素，1.0UI·kg，皮下注射）。将大鼠分为小（约17g）、大（约30g）肿瘤负荷组。
大肿瘤负荷大鼠表现出更严重的恶病质、血液三酰甘油和游离脂肪酸水平以及胰岛素抵抗。PGZ和PGZ+INS治疗并未改变肿瘤生长和食物摄入量，但减轻了小肿瘤负荷大鼠的一些异常情况，如胰岛素抵抗、血液游离脂肪酸增加、腹膜后脂肪消耗和体重减轻。腹膜后脂肪消耗的预防并不涉及肿瘤坏死因子-α表达的降低。在大肿瘤负荷大鼠中，PGZ和PGZ+INS治疗可逆转高血液三酰甘油和游离脂肪酸水平，但对其他参数无影响。
PGZ和PGZ+INS可能通过降低血液游离脂肪酸改善胰岛素外周敏感性，并减轻小肿瘤负荷大鼠的脂肪组织消耗和体重减轻。结果表明，PGZ在肿瘤较小即恶病质较轻时预防胰岛素抵抗、脂肪组织消耗和体重减轻具有临床益处。
