Chemotherapy diminishes lipid storage capacity of adipose tissue in a preclinical model of colon cancer

Lipids in Health and Disease

Research

Richard Lehner¹  Maryam Ebadi²  Catherine J. Field²  Vera C. Mazurak³ 

[1] Department of Pediatrics, Group on Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB, Canada;Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada;Division of Human Nutrition, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada;Faculty of Agricultural, Life & Environmental Science 4-002 Li Ka Shing Center for Research Innovation, University of Alberta, T6G 2E1, Edmonton, AB, Canada;

关键词: Adipose atrophy;    Cancer treatment;    Lipogenesis;    Lipid synthetic pathways;    Fatty acids;   

DOI  :  10.1186/s12944-017-0638-8

 received in 2017-11-06, accepted in 2017-12-05,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAccelerated loss of adipose tissue in cancer is associated with shorter survival, and reduced quality of life. Evidence is emerging suggesting tumour association with alterations in adipose tissue, but much less is known about drug-related mechanisms contributing to adipose atrophy. Identification of mechanisms by which tumour and cancer treatments, such as chemotherapy, affect adipose tissue are required to develop appropriate therapeutic interventions to prevent fat depletion in cancer. This pre-clinical study aimed to assess alterations in adipose tissue during the clinical course of cancer.MethodsFischer 344 rats bearing the Ward colorectal tumour were euthanized before chemotherapy, after 1- cycle, or 2-cycles of a combination chemotherapy consisting of Irinotecan (CPT-11) combined with 5-fluorouracil (5-FU), which recapitulates first line treatment for human colorectal cancer. Periuterine adipose tissue was isolated. Healthy rats served as a reference group. Histological analysis (hematoxylin and eosin), Real-time PCR (TaqMan) and proteomic analysis (LC-MS/MS) were performed.ResultsLarger adipocytes (3993.7 ± 52.6 μm2) in tumour-bearing animals compared to the reference group (3227.7 ± 36.7 μm2; p < 0.001) was associated with reduced expression of proteins involved in mitochondrial fatty acid oxidation. The presence of a tumour has a significant effect on phospholipid but not triglyceride fatty acid composition. There were greater proportions of saturated fatty acids concurrent with lower monounsaturated fatty acids within the PL fraction of adipocytes in tumour-bearing animals. Chemotherapy treatment decreased the size of adipocytes (2243.9 ± 30.4 μm2; p < 0.001) and led to depletion of n-3 polyunsaturated fatty acids in adipose tissue triglyceride. Evaluation of the proteome profile revealed decreased expression of proteins involved in ATP generation, β-oxidation, and lipogenesis. Overall, adipose tissue may not be able to efficiently oxidize fatty acids to provide energy to maintain energy demanding pathways like lipogenesis inside the tissue.ConclusionsIn conclusion, metabolic adaptations to mitochondrial impairment may contribute to diminished lipid storage capacity of adipose tissue following chemotherapy delivery.

【 授权许可】

CC BY   
© The Author(s). 2017