Cancer Metabolism Research Group, Institute of Biomedical Sciences and Faculdade de Medicina, University of São Paulo, São Paulo, Brazil; Biosciences Department, Universidade Federal de São Paulo (UNIFESP), Campus Baixada Santista, Santos, Brazil.
Exercise and Immunometabolism Research Group, Department of Physical Education, Universidade Estadual Paulista, Presidente Prudente, Brazil.
Clin Nutr. 2019 Oct;38(5):2219-2230. doi: 10.1016/j.clnu.2018.09.023. Epub 2018 Sep 25.
BACKGROUND & AIMS: The liver is the main organ regulating metabolism. In spite of that, few studies examine liver metabolism in cachexia, a wasting syndrome associated with increased morbidity and mortality in cancer. Cachexia induces major metabolic disruption, inflammation and fat and lean mass loss. We have previously shown impairment of hepatic lipid metabolism in cancer cachexia that contributes to the aggravation of the symptoms. The present study addresses the effects of Conjugated Linoleic Acid supplementation upon liver lipid metabolism in cachectic rats.
Male Wistar rats were randomly assigned to control groups (C) receiving 0.9 NaCl (Placebo CP); or to groups supplemented with sunflower oil (CSF), supplemented with CLA (CCLA), or still, to tumour bearing animals (T) receiving NaCl (TP), sunflower oil (TSF), or CLA (TCLA). Supplementation (0.5 ml) by gavage was carried out for 14 days. Body weight, dietary intake, glucose, cholesterol and triacylglycerol plasma content, liver glycogen and triacylglycerol content and mRNA expression of liver carnitine palmitoyltransferase I and II (CPT I and II), as well as microsomal triglyceride transfer protein (MTP), liver fatty acid-binding protein (L-FABP), peroxisome proliferator-activated receptor-alpha (PPAR-alpha), and apolipoprotein B (apoB), were assessed.
Liver CPT II activity was reduced in all groups, when compared with CP. Hepatic mRNA expression of MTP, apoB and FABP was reduced in TCLA, when compared with all groups. TCLA also presented increased hepatic and plasma triacylglycerol content, when compared with all T groups. Adipose tissue-derived inflammatory factors were assessed. No differences among the groups were observed in regard to Retro Peritoneal Adipose Tissue cytokine (IL-1β, IL-6, and TNF-α) protein content and expression, with the exception of IL-10 in tumour-bearing animals. In the Epididymal Adipose Tissue, the inflammatory cytokines were augmented in TCLA, compared with all other groups.
CLA supplementation fails to promote the re-establishment of hepatic lipid metabolism in tumour-bearing animals, and therefore is not recommended in cancer-related cachexia.
肝脏是调节代谢的主要器官。尽管如此，很少有研究探讨恶病质（一种与癌症相关的、发病率和死亡率增加的消耗综合征）中的肝脏代谢。恶病质会引起主要的代谢紊乱、炎症以及脂肪和瘦肉质量的损失。我们之前已经表明，癌症恶病质中的肝脂代谢受损会加重症状。本研究旨在探讨共轭亚油酸（CLA）补充对恶病质大鼠肝脏脂质代谢的影响。
雄性 Wistar 大鼠被随机分为对照组（C），给予 0.9%生理盐水（安慰剂 CP）；或给予葵花籽油（CSF）组、CLA 补充组（CCLA）或仍给予荷瘤动物组（T），分别给予生理盐水（TP）、葵花籽油（TSF）或 CLA（TCLA）。通过灌胃进行 14 天的补充（0.5ml）。评估体重、饮食摄入、血糖、胆固醇和三酰甘油的血浆含量、肝糖原和三酰甘油含量，以及肝脏肉毒碱棕榈酰转移酶 I 和 II（CPT I 和 II）的 mRNA 表达，以及微粒体甘油三酯转移蛋白（MTP）、肝脂肪酸结合蛋白（L-FABP）、过氧化物酶体增殖物激活受体-α（PPAR-α）和载脂蛋白 B（apoB）。
与 CP 相比，所有组的肝脏 CPT II 活性均降低。与所有组相比，TCLA 组的肝 MTP、apoB 和 FABP 的 mRNA 表达减少。与所有 T 组相比，TCLA 组还表现出肝和血浆三酰甘油含量增加。评估了来自脂肪组织的炎性因子。除荷瘤动物的 IL-10 外，各组间 Retro Peritoneal 脂肪组织的细胞因子（IL-1β、IL-6 和 TNF-α）蛋白含量和表达均无差异。在 Epididymal 脂肪组织中，与所有其他组相比，TCLA 组的炎性细胞因子增加。
CLA 补充未能促进荷瘤动物肝脏脂质代谢的重建，因此不建议在癌症相关的恶病质中使用。
