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Low Levels of Lipogenic Enzymes in Peritumoral Adipose Tissue of Colorectal Cancer Patients

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Lipids

Abstract

Lipoprotein lipase (LPL) is the crucial enzyme for intravascular catabolism of triglyceride-rich lipoproteins. Fatty acid synthase (FAS) is a key anabolic enzyme that catalyzes the terminal steps in the novo biosynthesis of 18:2n-6. The involvement of both LPL and FAS in tumor biology has been widely demonstrated in different studies and to verify whether there are regional differences in the expression of these enzymes in visceral adipose tissue from patients with colorectal cancer might be representative of events which sustain tumor growth. The objective of this study was to evaluate LPL and FAS activity and expression of their genes in adipose tissue adjacent to neoplasia and distant from it from patients operated for colorectal cancer. LPL enzymatic activity was evaluated by a fluorescent method and FAS activity by a radiometer assay. Reverse-transcription and real-time PCR were used to detect mRNA levels of two enzymes. Our findings show a significant reduction in both LPL and FAS gene expression and activity levels in adipose tissue adjacent to tumor lesion compared to those detected in paired tissue distant from neoplasia. These results underline the influence of tumor microenvironment on lipid metabolism in adipose tissue, demonstrating a tumor-induced impairment in the formation and lipid storing capacity of adipose tissue in patients with colorectal cancer.

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Abbreviations

LPL:

Lipoprotein lipase

FAS:

Fatty acid synthase

PCR:

Polymerase chain reaction

CRC:

Colorectal cancer

BMI:

Body mass index

EDTA:

Ethylenediaminetetraacetic acid

DTT:

Dithiothreitol

NADPH:

Nicotinamide adenine dinucleotide phosphate

CoA:

Coenzyme A

References

  1. Lang K, Ratke J (2009) Leptin and adiponectin: new players in the field of tumor cell and leukocyte migration. Cell Commun Signaling 7:27

    Article  Google Scholar 

  2. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89:2548–2556

    Article  PubMed  CAS  Google Scholar 

  3. Panarotto D, Poisson J, Devroede G, Maheux P (2000) Lipoprotein lipase steady-state mRNA levels are lower in human omental versus subcutaneous abdominal adipose tissue. Metabolism 49:1224–1227

    Article  PubMed  CAS  Google Scholar 

  4. Peiris AN, Sothmann MS, Hoffmann RG, Hennes MI, Wilson CR, Gustafson AB, Kissebah AH (1989) Adiposity, fat distribution and cardiovascular risk. Ann Intern Med 110:867–872

    PubMed  CAS  Google Scholar 

  5. Kissebah AH, Krakower GR (1994) Regional adiposity and morbidity. Physiol Res 74:761–811

    CAS  Google Scholar 

  6. Cerne D, Zitnik IP, Sok M (2010) Increased fatty acid synthase activity in non-small cell lung cancer tissue is a weaker predictor of shorter patient survival than increased lipoprotein lipase activity. Arch Med Res 41:405–409

    Article  PubMed  CAS  Google Scholar 

  7. Trost Z, Sok M, Marc J, Cerne D (2009) Increased lipoprotein lipase activity in non-small cell lung cancer tissue predicts shorter patient survival. Arch Med Res 40:364–368

    Article  PubMed  CAS  Google Scholar 

  8. Kuhajda FP (2000) Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition 16:202–208

    Article  PubMed  CAS  Google Scholar 

  9. Kuhajda FP (2006) Fatty acid synthase and cancer: new application of an old pathway. Cancer Res 66:5977–5980

    Article  PubMed  CAS  Google Scholar 

  10. Van de Sande T, Roskams T, Lerut E, Joniau S, Van Poppel H, Verhoeven G, Swinnen GV (2005) High levels expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB. J Pathol 206:214–219

    Article  PubMed  Google Scholar 

  11. Rashid A, Pizer ES, Moga M, Milgraum LZ, Zahurak M, Pastermack GR, Kuhajda FP, Hamilton SR (1997) Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol 150:201–208

    PubMed  CAS  Google Scholar 

  12. Visca P, Alo PL, Del Nonno F, Botti C, Trombetta G, Marandino F, Filippi S, Di Tondo U, Perrone Donnorso R (1999) Immunohistochemical expression of fatty acid synthase, apoptotic-regulating genes, proliferating factors, and Ras protein product in nonneoplastic mucosa. Clin Cancer Res 5:4111–4118

    PubMed  CAS  Google Scholar 

  13. Notarnicola M, Altomare DF, Calvani M, Orlando A, Bifulco M, D’Attoma B, Caruso MG (2006) Fatty acid synthase hyperactivation in human colorectal cancer: relationship with tumor side and sex. Oncology 71:327–332

    Article  PubMed  CAS  Google Scholar 

  14. Mori R, Wang Q, Danenberg KD, Pinski JK, Danenberg PV (2008) Both β-actin and GAPDH are useful reference genes fr normalization of quantitative RT-PCR in human FFPE tissue samples of prostate cancer. Prostate 68:1555–1560

    Article  PubMed  CAS  Google Scholar 

  15. Farah IO (2007) Differential modulation of intracellular energetics in A549 and MRC-5 cells. Biomed Sci Instrum 43:110–115

    PubMed  CAS  Google Scholar 

  16. Sakayama K, Masuno H, Miyazaki T, Okumura H, Shibata T, Okuda H (1994) Existence of lipoprotein lipase in human sarcomas and carcinomas. Jpn J Cancer Res 85:515–521

    Article  PubMed  CAS  Google Scholar 

  17. Bing C, Russel S, Becket E, Pope M, Tisdale MJ, Trayhurn P, Jenkins JR (2006) Adipose atrophy in cancer cachexia: morphologic and molecular analysis of adipose tissue in tumour-bearing mice. B J Cancer 95:1028–1037

    Article  CAS  Google Scholar 

  18. Bianchini F, Kaaks R, Vainio H (2002) Overweight, obesity and cancer risk. Lancet Oncol 3:565–574

    Article  PubMed  Google Scholar 

  19. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348:1625–1638

    Article  PubMed  Google Scholar 

  20. Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4:579–591

    Article  PubMed  CAS  Google Scholar 

  21. Amemori S, Ootani A, Aoki S, Fujise T, Shimoda R, Kakimoto T, Shiraishi R, Sakata Y, Tsunada S, Iwakiri R, Fujimoto K (2007) Adipocytes and preadipocytes promote the proliferation of colon cancer cells in vitro. Am J Physiol Gastrointest Liver Physiol 292:G923–G929

    Article  PubMed  CAS  Google Scholar 

  22. Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP (2001) Leptin is a growth factor for colonic epithelial cells. Gastroenterology 121:79–90

    Article  PubMed  CAS  Google Scholar 

  23. Tamakoshi K, Toyoshima H, Wkai K, Kojima M, Suzuki K, Watanabe Y, Hayakawa N, Yatsuya H, Kondo T, Tokudome S, Hashimoto S, Suzuk S, Kawado M, Ozasa K, Ito Y, Tamakoshi A (2005) Leptin is associated with increased female colorectal cancer risk: a nested case-control study in Japan. Oncology 68:454–461

    Article  PubMed  CAS  Google Scholar 

  24. Thompson MP, Koons JE, Tan ETH, Grigor MR (1981) Modified lipoprotein lipase activities, rates of lipogenesis, and lipolysis as factors leading to lipid depletion in C57BL mice bearing the preputial gland tumor, ESR-586. Cancer Res 41:3228–3232

    PubMed  CAS  Google Scholar 

  25. Lanza-Jacoby S, Lansey SC, Miller EE, Cleary MP (1984) Sequential changes in the activities of lipoprotein lipase and lipogenic enzymes during tumor growth in rats. Cancer Res 44:5062–5067

    PubMed  CAS  Google Scholar 

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The authors declare that they have no conflict of interest.

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Correspondence to Maria Notarnicola.

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Notarnicola, M., Miccolis, A., Tutino, V. et al. Low Levels of Lipogenic Enzymes in Peritumoral Adipose Tissue of Colorectal Cancer Patients. Lipids 47, 59–63 (2012). https://doi.org/10.1007/s11745-011-3630-5

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  • DOI: https://doi.org/10.1007/s11745-011-3630-5

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