Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation

Author(s)

Goncalves, Daniela Caetano ^{[1, 2, 3]} ; Lira, Fabio Santos ^[4] ; Yamashita, Alex Shimura ^{[1, 2]} ; Carnevali Junior, Luiz Carlos ^{[1, 2]} ; Eder, Robson ^{[1, 2]} ; Laviano, Alessandro ^[5] ; Leite Seelaender, Marilia Cerqueira ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Canc Metab Res Grp, Inst Biomed Sci, Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo UNIFESP, Biosci Dept, Campus Baixada Santista, Santos - Brazil

^[4] Univ Estadual Paulista, Exercise & Immunometab Res Grp, Dept Phys Educ, Presidente Prudente - Brazil

^[5] Sapienza Univ Rome, Dept Clin Med, Rome - Italy

• Document type: Journal article
• Source: Clinical Nutrition; v. 38, n. 5, p. 2219-2230, OCT 2019.
• Web of Science Citations: 1

Abstract

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. Methods: 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. Results: 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-1 beta, IL-6, and TNF-alpha) 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. Conclusion: 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. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. (AU)

• FAPESP's process: 12/50079-0 - Systemic inflammation in cachectic cancer patients: mechanisms and therapeutical strategies, a translational medicine approach
• Grantee: Marilia Cerqueira Leite Seelaender
• Support Opportunities: Research Projects - Thematic Grants