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

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.

Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic ApcMin/+ Mice, Correlating with CB1 Receptor Up-Regulation

“…We have previously demonstrated that adipose and colon tissue interact, affecting the enzymatic activity of proteins involved in lipogenesis and cell proliferation [17]. Moreover, pronounced morphologic and molecular alterations of adipose tissue have been observed in tumor-bearing mice [18].…”

“…Moreover, pronounced morphologic and molecular alterations of adipose tissue have been observed in tumor-bearing mice [18]. Several studies have found a trophic effect of adipose tissue on colon cancer cell growth [17,19,20,21]. …”

Cross-Kingdom Regulation of Putative miRNAs Derived from Happy Tree in Cancer Pathway: A Systems Biology Approach

“…Further, the alterations in major components of the mTOR pathway like loss of function of PTEN , PI3K amplification/mutation and over-expression of S6K1 , 4EBP1 , eIF4E and AKT have been reported to be associated with many types of cancers, particularly in melanoma and glioblastama [55,56]. While, the decreased levels of lipogenic enzymes Lipoprotein lipase (LPL) and Fatty acid synthase (FAS), important components of the regulation of lipolysis in adipocytes pathway was reported to be associated with colorectal cancer [57]. …”

mTOR and Tumor Cachexia

“…Decreased activity of fatty acid synthase and lipoprotein lipase was shown in adipose tissue of cancer patients [48] and adipogenesis, a process essential to form mature adipocytes, is impaired in experimental models of cancer cachexia with reduced expression of adipogenic transcription factors [44,49,50]. …”