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Cancer Biology & Therapy Dec 2024Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of...
Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear. In the present study, we aimed to investigate the functional impact of linoleic acid on cell proliferation, invasion, and tumor growth in endometrial cancer cells and in a transgenic mouse model of endometrial cancer. The results showed that Linoleic acid significantly inhibited the proliferation of endometrial cancer cells in a dose-dependent manner. The treatment of HEC-1A and KLE cells with linoleic acid effectively increased intracellular reactive oxygen species (ROS) production, decreased mitochondrial membrane potential, caused cell cycle G1 arrest, and induced intrinsic and extrinsic apoptosis pathways. The anti-invasive ability of linoleic acid was found to be associated with the epithelial-mesenchymal transition process in both cell lines, including the decreased expression of N-cadherin, snail, and vimentin. Furthermore, treatment of transgenic mice with linoleic acid for four weeks significantly reduced the growth of endometrial tumors and decreased the expression of VEGF, vimentin, Ki67, and cyclin D1 in tumor tissues. Our findings demonstrate that linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cell lines and the mouse model of endometrial cancer, thus providing a pre-clinical basis for future dietary interventions with linoleic acid in endometrial cancer.
Topics: Humans; Female; Mice; Animals; Vimentin; Linoleic Acid; Cell Line, Tumor; Tumor Suppressor Protein p53; Endometrial Neoplasms; Carcinogenesis; Cell Proliferation
PubMed: 38465855
DOI: 10.1080/15384047.2024.2325130 -
Advances in Nutrition (Bethesda, Md.) Nov 2015Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most... (Review)
Review
Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time.
Topics: Adipose Tissue; Adult; Diet; Dietary Fats, Unsaturated; Humans; Linoleic Acid; Subcutaneous Fat; United States
PubMed: 26567191
DOI: 10.3945/an.115.009944 -
Nutrients Jul 2023Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free...
Linoleic acid (LA) is an essential omega-6 polyunsaturated fatty acid (PUFA) derived from the diet. Sebocytes, whose primary role is to moisturise the skin, process free fatty acids (FFAs) to produce the lipid-rich sebum. Importantly, like other sebum components such as palmitic acid (PA), LA and its derivative arachidonic acid (AA) are known to modulate sebocyte functions. Given the different roles of PA, LA and AA in skin biology, the aim of this study was to assess the specificity of sebocytes for LA and to dissect the different roles of LA and AA in regulating sebocyte functions. Using RNA sequencing, we confirmed that gene expression changes in LA-treated sebocytes were largely distinct from those induced by PA. LA, but not AA, regulated the expression of genes related to cholesterol biosynthesis, androgen and nuclear receptor signalling, keratinisation, lipid homeostasis and differentiation. In contrast, a set of mostly down-regulated genes involved in lipid metabolism and immune functions overlapped in LA- and AA-treated sebocytes. Lipidomic analyses revealed that the changes in the lipid profile of LA-treated sebocytes were more pronounced than those of AA-treated sebocytes, suggesting that LA may serve not only as a precursor of AA but also as a potent regulator of sebaceous lipogenesis, which may not only influence the gene expression profile but also have further specific biological relevance. In conclusion, we have shown that sebocytes are able to respond selectively to different lipid stimuli and that LA-induced effects can be both AA-dependent and independent. Our findings allow for the consideration of LA application in the therapy of sebaceous gland-associated inflammatory skin diseases such as acne, where lipid modulation and selective targeting of AA metabolism are potential treatment options.
Topics: Palmitic Acid; Arachidonic Acid; Linoleic Acid; Sebaceous Glands; Sebum; Lipogenesis
PubMed: 37571253
DOI: 10.3390/nu15153315 -
Biochemical and Biophysical Research... May 2019Elevated saturated free fatty acid levels during over-nutrition lead to hypothalamic inflammation, which perturbs energy homeostasis. Whether brain-derived metabolites...
Elevated saturated free fatty acid levels during over-nutrition lead to hypothalamic inflammation, which perturbs energy homeostasis. Whether brain-derived metabolites are coupled to the development of obesity pathogenesis during the early over-nutrition period has not been thoroughly investigated. In this study, we found increased linoleic acid, an unsaturated fatty acid, in both the whole brain and hypothalamus of mice fed a high-fat diet for 4 weeks. Furthermore, we observed that linoleic acid effectively reversed the inflammatory responses induced by palmitic acid treatment in microglial cells. Collectively, this study suggests the reversible function of linoleic acid on brain inflammation in association with microglial activation during short-term exposure to a high-fat diet.
Topics: Animals; Anti-Inflammatory Agents; Diet, High-Fat; Encephalitis; Linoleic Acid; Mice, Inbred C57BL; Microglia; Palmitic Acid
PubMed: 30952426
DOI: 10.1016/j.bbrc.2019.03.047 -
Prostaglandins, Leukotrienes, and... 2008Linoleic acid is the most prominent polyunsaturated fatty acid (PUFA) in the Western diet. It is virtually found in every food we eat and is the predominant PUFA in... (Review)
Review
Linoleic acid is the most prominent polyunsaturated fatty acid (PUFA) in the Western diet. It is virtually found in every food we eat and is the predominant PUFA in land-based meats, dairy, vegetables, vegetable oils, cereals, fruits, nuts, legumes, seeds and breads. Because linoleic acid is the metabolic precursor of arachidonic acid and bioactive eicosanoids derived from arachidonic acid, there is concern that dietary linoleic acid could augment tissue arachidonic acid content, eicosanoid formation and subsequently enhance the risk of and/or exacerbate conditions associated with acute and chronic diseases (i.e., cancers, cardiovascular disease, inflammation, neurological disorders, etc.). The following series of papers examines the impact of modifying dietary levels of linoleic acid on health outcomes. The authors were asked to start with current intakes of linoleic acid (adults) and determine if health outcomes would change if linoleic acid intake increased or decreased. The authors addressed changes in tissue arachidonic acid content and eicosanoid formation, cardiovascular disease, inflammation, and psychiatric disorders.
Topics: Arachidonic Acid; Cardiovascular Diseases; Dietary Fats; Eicosanoids; Humans; Inflammation; Linoleic Acid; Mental Disorders
PubMed: 18990554
DOI: 10.1016/j.plefa.2008.09.013 -
Prostaglandins, Leukotrienes, and... 2008The extent to which higher intakes of linoleic acid (LA) affect risk for coronary heart disease (CHD) is examined by reviewing a wide variety of study types, mostly in... (Review)
Review
The extent to which higher intakes of linoleic acid (LA) affect risk for coronary heart disease (CHD) is examined by reviewing a wide variety of study types, mostly in humans. In experimental studies, LA has been shown to lower serum levels of low-density lipoprotein cholesterol (LDL-C), especially when substituted for saturated fatty acids. Such an effect would be expected to reduce risk for CHD. In observational studies in which the dietary intake or serum content of LA were either cross-sectionally or prospectively related risk for CHD, higher LA intakes or serum levels have usually been associated with reduced risk. The pooled results from 5 randomized trials where LA was substituted for saturated fatty acids revealed a significant decrease in risk for CHD events with an LA intake 2-3 times current levels. Thus, current recommendations to consume 5-10% of energy from LA are evidence-based, and should not be reduced.
Topics: Cholesterol, LDL; Coronary Disease; Dietary Fats; Evidence-Based Medicine; Humans; Linoleic Acid; Randomized Controlled Trials as Topic; Risk Factors
PubMed: 18951772
DOI: 10.1016/j.plefa.2008.09.005 -
Public Health Nutrition Jun 2016Prior studies on linoleic acid, the predominant n-6 fatty acid, and breast cancer risk have generated inconsistent results. We performed a meta-analysis to summarize the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Prior studies on linoleic acid, the predominant n-6 fatty acid, and breast cancer risk have generated inconsistent results. We performed a meta-analysis to summarize the evidence regarding the relationship of dietary and serum linoleic acid with breast cancer risk.
DESIGN
Pertinent studies were identified by a search of PubMed and EMBASE. The fixed- or random-effect pooled measure was selected based on between-study heterogeneity.
RESULTS
Eight prospective cohort studies and four prospective nested case-control studies, involving 10 410 breast cancer events from 358 955 adult females across different countries, were included in present study. Compared with the lowest level of linoleic acid, the pooled relative risk (RR; 95 % CI) of breast cancer was 0·98 (0·93, 1·04) for the highest level of linoleic acid. The pooled RR (95 % CI) for dietary and serum linoleic acid were 0·99 (0·92, 1·06) and 0·98 (0·88, 1·08), respectively. The RR (95 % CI) of breast cancer was 0·97 (0·91, 1·04), 0·95 (0·85, 1·07), 0·96 (0·86, 1·07), 0·98 (0·87, 1·10) and 0·99 (0·85, 1·14) for linoleic acid intake of 5, 10, 15, 20 and 25 g/d, respectively. The risk of breast cancer decreased by 1 % (RR=0·99; 95 % CI 0·93, 1·05) for every 10 g/d increment in linoleic acid intake.
CONCLUSIONS
This meta-analysis indicated that both dietary linoleic acid intake and serum linoleic acid level were associated with decreased risk of breast cancer, although none of the associations were statistically significant. Further investigations are warranted.
Topics: Breast Neoplasms; Diet; Female; Humans; Linoleic Acid; Risk Factors
PubMed: 26434699
DOI: 10.1017/S136898001500289X -
Scientific Reports Mar 2024Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA)...
Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS.
Topics: Female; Humans; Reactive Oxygen Species; Linoleic Acid; Polycystic Ovary Syndrome; Receptors, Estrogen; Granulosa Cells; Apoptosis; Inflammation; Forkhead Box Protein O1
PubMed: 38493198
DOI: 10.1038/s41598-024-56970-x -
Journal of the American College of... Aug 2000Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce... (Review)
Review
Osteoporosis, osteoarthritis and inflammatory joint disease afflict millions of people worldwide. Inflammatory cytokines inhibit chondrocyte proliferation and induce cartilage degradation for which part of the response is mediated by PGE2. Excess production of PGE2 is linked to osteoporosis and arthritis and is associated with bone and proteoglycan loss. PGE2 also influences the IGF-I/IGFBP axis to facilitate bone and cartilage formation. Recent investigations with growing rats given butter fat and supplements of CLA demonstrated an increased rate of bone formation and reduced ex vivo bone PGE2 production, respectively. Furthermore, the supplements of CLA isomers resulted in their enrichment in lipids of various bone compartments of animals. The effects of CLA on bone biology in rats (IGF action and cytokines) appear to be dependent on the level of n-6 and n-3 fatty acids in the diet; however, these studies generally showed that CLA decreased ex vivo bone PGE2 production and in osteoblast-like cultures. Anti-inflammatory diets, including nutraceutical applications of CLA, may be beneficial in moderating cyclooygenase 2 (COX-2) activity or expression (influencing PGE2 biosynthesis) and might help to reduce rheumatoid arthritis (secondary osteoporosis). This review summarizes findings of CLA on bone modeling in rats and effects on cellular functions of osteoblasts and chondrocytes. These experiments indicate that CLA isomers possess anti-inflammatory activity in bone by moderating prostanoid formation.
Topics: Animals; Bone Development; Bone Remodeling; Bone and Bones; Cartilage; Cytokines; Dietary Fats, Unsaturated; Humans; In Vitro Techniques; Linoleic Acid; Prostaglandins
PubMed: 10963468
DOI: 10.1080/07315724.2000.10718951 -
Annals of the New York Academy of... Sep 2021Previous studies suggest that squalene (SQ) in sebum is oxidized by a photooxidation mechanism (i.e., singlet oxygen oxidation) to create SQ hydroperoxide (SQOOH), a...
Previous studies suggest that squalene (SQ) in sebum is oxidized by a photooxidation mechanism (i.e., singlet oxygen oxidation) to create SQ hydroperoxide (SQOOH), a compound that causes adverse skin conditions. However, oxidation of other lipids in sebum, such as linoleic acid (LA), has not been fully understood. Elucidating their oxidation, especially its mechanisms, may lead to a further understanding of the relationship between sebum oxidation and skin conditions. In this study, using HPLC-MS/MS, we aimed to detect LA hydroperoxide (LAOOH) directly from sebum and identify the oxidation mechanism of LA in sebum through analysis of LAOOH isomers. We developed extraction and HPLC-MS/MS analysis conditions that can sufficiently quantify each LAOOH isomer in sebum. Using this method, LAOOH was detected in samples from healthy individuals, demonstrating the presence of LAOOH in human sebum. Moreover, isomer analysis of LAOOH and SQOOH indicated that LA and SQ are oxidized in sebum by discrete oxidation mechanisms (LA oxidized by free radical oxidation, whereas SQ oxidized by singlet oxygen oxidation). Such results may further lead to the development of mechanism-specific ways to prevent oxidation of sebum via a selection of appropriate antioxidants, ultimately leading to the promotion of skin health.
Topics: Carbohydrate Metabolism; Chromatography, High Pressure Liquid; Female; Humans; Linoleic Acid; Lipid Metabolism; Male; Metabolomics; Oxidation-Reduction; Sebum; Solid Phase Extraction; Squalene; Tandem Mass Spectrometry
PubMed: 34060095
DOI: 10.1111/nyas.14615