Altered metabolism of lipids is currently considered a hallmark characteristic of many malignancies, including colorectal cancer (CRC). Lipids are a large group of metabolites that differ in terms of their fatty acid composition. This review summarizes recent evidence, documenting many alterations in the content and composition of fatty acids, polar lipids, oxylipins and triacylglycerols in CRC patients’ sera, tumor tissues and adipose tissue. Some of altered lipid molecules may be potential biomarkers of CRC risk, development and progression. Owing to a significant role of many lipids in cancer cell metabolism, some of lipid metabolism pathways may also constitute specific targets for anti-CRC therapy.
Objective: While small amounts of odd-chain fatty acids (OCFAs) and branched-chain fatty acids (BCFAs) were known to be present in mammals, it was quite recently that they were shown to play an important role in human health. However, still little is known on OCFA and BCFA profiles in subjects who have obesity. The aim of this study was to verify whether obesity is associated with changes in serum OCFA and BCFA profiles. Methods: Serum content of fatty acids was determined by gas chromatography-mass spectroscopy in 23 patients with excess weight and 21 nonobese controls. Results: Six OCFAs and six BCFAs (three iso-BCFAs and three anteiso-BCFAs) were found in sera from the examined subjects. Patients with excess weight presented with significantly lower serum iso-BCFA levels than the controls. Total serum content of iso-BCFAs correlated inversely with serum insulin, triglycerides, and 18:1/18:0 desaturation index. Both OCFA and iso-BCFA levels correlated inversely with Creactive protein concentration. Conclusions: Lower iso-BCFA content in patients with excess weight may be involved in elevation of serum concentration of triglycerides and inflammation. Decreased contents of iso-BCFAs in subjects with have obesity, and established anti-inflammatory, antidiabetic, and anticancer properties of these fatty acids, point to potential beneficial effects of an iso-BCFA-rich diet.
Increased physical activity is an optimal way to maintain a good health. During exercise, triacylglycerols, an energy reservoir in adipose tissue, are hydrolyzed to free fatty acids (FAs) which are then released to the circulation, providing a fuel for working muscles. Thus, regular physical activity leads to a reduction of adipose tissue mass and improves metabolism. However, the reduction of lipid reservoir is also associated with many other interesting changes in adipose tissue FA metabolism. For example, a prolonged exercise contributes to a decrease in lipoprotein lipase activity and resultant reduction of FA uptake. This results in the improvement of mitochondrial function and upregulation of enzymes involved in the metabolism of polyunsaturated fatty acids. The exercise-induced changes in adipocyte metabolism are associated with modifications of FA composition. The modifications are adipose tissue depot-specific and follow different patterns in visceral and subcutaneous adipose tissue. Moreover, exercise affects adipokine release from adipose tissue, and thus, may mitigate inflammation and improve insulin sensitivity. Another consequence of exercise is the recently described phenomenon of adipose tissue “beiging,” i.e., a switch from energy-storing white adipocyte phenotype to thermogenic FA oxidizing beige adipocytes. This process is regulated by myokines released during the exercise. In this review, we summarize published evidence for the exercise-related changes in FA metabolism and adipokine release in adipose tissue, and their potential contribution to beneficial cardiovascular and metabolic effects of physical activity.
Obesity is a major contributor to the dysfunction of liver, cardiac, pulmonary, endocrine and reproductive system, as well as a component of metabolic syndrome. Although development of obesity-related disorders is associated with lipid abnormalities, most previous studies dealing with the problem in question were limited to routinely determined parameters, such as serum concentrations of triacylglycerols, total cholesterol, low-density and high-density lipoprotein cholesterol. Many authors postulated to extend the scope of analysed lipid compounds and to study obesity-related alterations in other, previously non-examined groups of lipids. Comprehensive quantitative, structural and functional analysis of specific lipid groups may result in identification of new obesity-related alterations. The review summarizes available evidence of obesity-related alterations in various groups of lipids and their impact on health status of obese subjects. Further, the role of diet and endogenous lipid synthesis in the development of serum lipid alterations is discussed, along with potential application of various lipid compounds as risk markers for obesity-related comorbidities.
Background Subjects with morbid obesity have low levels of serum branched-chain fatty acids (BCFAs), which correlate inversely with insulin resistance, hypertriglyceridemia, and inflammation. Recent evidence suggests BCFAs are produced during branched-chain amino acid (BCAA) catabolism in human adipose tissue. Elevated concentrations of BCAAs are associated with insulin resistance. Objectives In this single-center study, we evaluated the effect of one anastomosis gastric bypass (OAGB) on circulating BCFA and BCAA. Moreover, we determined the expression of genes involved in BCAA catabolism in adipose tissue of patients with obesity and lean controls. Methods Fasting levels of BCFAs and BCAAs were determined by gas and liquid chromatography, respectively, coupled with mass spectrometry, in 50 patients with morbid obesity before and 6-9 months after surgery, and in 32 lean controls. Visceral and subcutaneous adipose tissue (VAT and SAT, respectively) biopsies were collected at baseline to determine mRNA levels for enzymes involved in BCAA catabolism. Results Before surgery, patients with obesity had lower BCFAs and greater BCAAs than control subjects. OAGB increased BCFA and decreased BCAA levels. Insulin resistance (assessed by HOMA) correlated inversely with BCFAs and positively with BCAAs. Expression of genes involved in BCAA catabolism in VAT (but not SAT) was lower in patients with obesity than in lean controls.
Although a growing body of evidence suggests that colorectal cancer (cRc) is associated with alterations of fatty acid (FA) profiles in serum and tumor tissues, available data about polyunsaturated fatty acid (pUfA) content in cRc patients are inconclusive. our study showed that cRc tissues contained more pUfAs than normal large intestinal mucosa. However, serum levels of pUfAs in cRc patients were lower than in healthy controls. to explain the mechanism of pUfA alterations in cRc, we measured fA uptake by the colon cancer cells and normal colon cells. the levels of pUfAs in colon cancer cell culture medium decreased significantly with incubation time, while no changes were observed in the medium in which normal colon cells were incubated. Our findings suggest that the alterations in tumor and serum PUFA profiles result from preferential uptake of these FAs by cancer cells; indeed, PUFAs are essential for formation of cell membrane phospholipids during rapid proliferation of cancer cells. this observation puts into question potential benefits of PUFA supplementation in CRC patients.
Fatty acids containing a cyclopropane ring in their structure (cyclopropane FA) have been found in a wide variety of bacteria, a number of protozoa, and Myriapoda. Little is known about cyclopropane FA in mammal, especially in human tissues. The present study deals with the identification of cyclopropane FA in adipose tissue and serum of humans and rats. Fatty acids extracted from the adipose tissue and serum obtained from obese women during bariatric surgery were methylated and analyzed on GC–MS. We have identified: cyclopropaneoctanoic acid 2-hexyl, cyclopropaneoctanoic acid 2-octyl, cyclopropanenonanoic acid, and 2-[[2-[(2-ethylcyclopropyl)methyl]cyclopropyl]methyl] acid in human adipose tissue. We confirmed the presence of cyclopropaneoctanoic acid 2-hexyl by derivatization of FA extracted from human adipose tissue to picolinyl esters. Cyclopropaneoctanoic acid 2-hexyl was the main cyclopropane FA (approximately 0.4 % of total fatty acids in human adipose tissue, and about 0.2 % of total fatty acids in the serum). In adipose tissue cyclopropaneoctanoic acid 2-hexyl was found mainly in triacylglycerols, whereas in serum in phospholipids and triacylglycerols. The cyclopropaneoctanoic acid 2-hexyl has also been found in serum, and adipose tissue of rats in amounts comparable to humans. The content of cyclopropaneoctanoic acid 2-hexyl decreased in adipose tissue of rats maintained on a restricted diet for 1 month. In conclusion, we demonstrated that cyclopropaneoctanoic acid 2-hexyl is present in human adipose tissue and serum. Adipose tissue cyclopropaneoctanoic acid 2-hexyl is stored mainly in triacylglycerols and the storage of this cyclopropane FA is affected by food restriction.
Backgrounds/Aims: Colorectal cancer (CRC) cells show some alterations of lipid metabolism. Elongation of fatty acids (FA) has not been studied in CRC tissues thus far. The aim of this study was to verify if CRC specimens and normal colon mucosa differ in terms of their levels of very long-chain FAs, a product of FA elongation. Moreover, the expression of elongase genes has been studied in normal tissue and CRC. Finally, we searched for some specific products of FA elongation in serum of CRC patients. Methods: The specimens of normal colon mucosa and CRC were obtained from nineteen CRC patients differ in terms of FA elongation. We also searched for some specific products of FA elongation in serum of CRC patients and from healthy volunteers. Tissue and serum FA profiles were determined by means of gas chromatography-mass spectrometry (GC/MS), and the tissue expression of elongases (ELOVLs) was analyzed with real-time PCR. Results: Compared to normal colon tissue, CRC specimens showed significantly higher levels of 22-, 24- and 26-carbon FAs, stronger expressions of ELOVL1 and ELOVL6 (4- and 9-fold elevated respectively), and higher values of 18: 0/16: 0 elongation index. We also demonstrated presence of cerotic acid (26: 0) in serum of all CRC patients but in none of the healthy controls. Conclusions: CRC tissue seems to be characterized by enhanced FA elongation (hyper-elongation). Presence of cerotic acid in CRC patients sera and absence of this FA in healthy subjects points to this compound as a strong candidate for specific metabolic marker of colorectal malignancies.
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