TY - JOUR
T1 - Liver lipid metabolism disruption in cancer cachexia is aggravated by cla supplementation -induced inflammation
AU - Gonçalves, Daniela Caetano
AU - Lira, Fábio Santos
AU - Yamashita, Alex Shimura
AU - Carnevali Junior, Luiz Carlos
AU - Eder, Robson
AU - Laviano, Alessandro
AU - Seelaender, Marília Cerqueira Leite
N1 - Funding Information:
To our sponsors: FAPESP ( 2012/50079-0 ), CAPES (Scholarship), CNPq (Scholarship). The authors would to thank Ms. Rosana Prisco and Ms. Emilia Ribeiro, for the excellent technical support.
Publisher Copyright:
© 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism
PY - 2019/10
Y1 - 2019/10
N2 - 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 [sbnd]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-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. 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.
AB - 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 [sbnd]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-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. 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.
KW - CLA
KW - Cachexia
KW - Inflammation
KW - Lipid metabolism
KW - Liver
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U2 - 10.1016/j.clnu.2018.09.023
DO - 10.1016/j.clnu.2018.09.023
M3 - Article
C2 - 30322784
AN - SCOPUS:85054696313
SN - 0261-5614
VL - 38
SP - 2219
EP - 2230
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 5
ER -