Beluzi Mércia, Peres Sidney B, Henriques Felipe S, Sertié Rogério A L, Franco Felipe O, Santos Kaltinaitis B, Knobl Pâmela, Andreotti Sandra, Shida Cláudio S, Neves Rodrigo X, Farmer Stephen R, Seelaender Marília, Lima Fábio B, Batista Miguel L
Laboratory of Adipose Tissue Biology, Integrated Group of Biotechnology, University of Mogi das Cruzes, Mogi das Cruzes, Brazil.
Department of Physiological Sciences, State University of Maringá, Paraná, Brazil.
PLoS One. 2015 Mar 25;10(3):e0122660. doi: 10.1371/journal.pone.0122660. eCollection 2015.
Cachexia is a multifactorial syndrome characterized by profound involuntary weight loss, fat depletion, skeletal muscle wasting, and asthenia; all symptoms are not entirely attributable to inadequate nutritional intake. Adipose tissue and skeletal muscle loss during cancer cachexia development has been described systematically. The former was proposed to precede and be more rapid than the latter, which presents a means for the early detection of cachexia in cancer patients. Recently, pioglitazone (PGZ) was proposed to exhibit anti-cancer properties, including a reduction in insulin resistance and adipose tissue loss; nevertheless, few studies have evaluated its effect on survival. For greater insight into a potential anti-cachectic effect due to PGZ, 8-week-old male Wistar rats were subcutaneously inoculated with 1 mL (2×107) of Walker 256 tumor cells. The animals were randomly assigned to two experimental groups: TC (tumor + saline-control) and TP5 (tumor + PGZ/5 mg). Body weight, food ingestion and tumor growth were measured at baseline and after removal of tumor on days 7, 14 and 26. Samples from different visceral adipose tissue (AT) depots were collected on days 7 and 14 and stored at -80o C (5 to 7 animals per day/group). The PGZ treatment showed an increase in the survival average of 27.3% (P< 0.01) when compared to TC. It was also associated with enhanced body mass preservation (40.7 and 56.3%, p< 0.01) on day 14 and 26 compared with the TC group. The treatment also reduced the final tumor mass (53.4%, p<0.05) and anorexia compared with the TC group during late-stage cachexia. The retroperitoneal AT (RPAT) mass was preserved on day 7 compared with the TC group during the same experimental period. Such effect also demonstrates inverse relationship with tumor growth, on day 14. Gene expression of PPAR-γ, adiponectin, LPL and C/EBP-α from cachectic rats was upregulated after PGZ. Glucose uptake from adipocyte cells (RPAT) was entirely re-established due to PGZ treatment. Taken together, the results demonstrate beneficial effects of PGZ treatment at both the early and final stages of cachexia.
恶病质是一种多因素综合征，其特征为严重的非自愿体重减轻、脂肪消耗、骨骼肌萎缩和乏力；所有症状并非完全归因于营养摄入不足。癌症恶病质发展过程中脂肪组织和骨骼肌的丢失已得到系统描述。前者被认为先于后者发生且速度更快，这为癌症患者恶病质的早期检测提供了一种方法。最近，吡格列酮（PGZ）被认为具有抗癌特性，包括降低胰岛素抵抗和减少脂肪组织丢失；然而，很少有研究评估其对生存期的影响。为了更深入了解PGZ潜在的抗恶病质作用，将8周龄雄性Wistar大鼠皮下接种1 mL（2×107）Walker 256肿瘤细胞。动物被随机分为两个实验组：TC（肿瘤+生理盐水对照）和TP5（肿瘤+PGZ/5 mg）。在第7、14和26天测量基线及去除肿瘤后的体重、食物摄入量和肿瘤生长情况。在第7天和14天从不同内脏脂肪组织（AT）库采集样本并储存在-80℃（每组每天5至7只动物）。与TC组相比，PGZ治疗使平均生存期提高了27.3%（P<0.01）。与TC组相比，在第14天和26天，PGZ治疗还与体重维持增加（分别为40.7%和56.3%，p<0.01）相关。在晚期恶病质阶段，与TC组相比，该治疗还减少了最终肿瘤质量（53.4%，p<0.05）和厌食症状。在同一实验期间，与TC组相比，第7天腹膜后AT（RPAT）质量得以保留。在第14天，这种作用也与肿瘤生长呈负相关。PGZ治疗后，恶病质大鼠的PPAR-γ、脂联素、脂蛋白脂肪酶（LPL）和C/EBP-α基因表达上调。由于PGZ治疗，脂肪细胞（RPAT）的葡萄糖摄取完全恢复。综上所述，结果表明PGZ治疗在恶病质的早期和晚期均具有有益作用。
