scholarly journals CBMT-05. GENETIC AND EPIGENETIC MECHANISMS REGULATING SCD INHIBITOR SENSITIVITY IN GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi33-vi33
Author(s):  
Nicole Oatman ◽  
Nupur Dasgupta ◽  
Biplab Dasgupta ◽  
Kwangmin Choi ◽  
Mruniya Gawali ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Human Cancer ◽  
Saturated Fatty Acids ◽  
Acquired Resistance ◽  
Monounsaturated Fatty Acids ◽  
Integral Membrane Protein ◽  
Drug Induced ◽  
Driver Genes ◽  
Hypoxic Conditions ◽  
Cell Alterations

Abstract A status-quo in targeted cancer therapy is that out of the thousands of somatic alterations found in a cancer cell, alterations only in driver genes determine therapeutic strategy. Despite unimpressive results of some driver-targeted therapies, and given that the majority of genomic alterations in cancer are not ‘drivers’, but ‘passengers’ / bystander alterations, it remains underappreciated whether targeting built-in vulnerabilities imposed by passenger gene alterations may provide therapeutic value. The tumor suppressor PTEN undergoes widespread functional inactivation including deletion in human cancer. PTEN deletion occurs frequently in GBM, sometimes as part of the 10q loss or chromosome 10 monosomy. We discovered that several genes including Stearoyl Co-A Desaturase, SCD (10q24.31), located 12 MB telomeric to PTEN is frequently co-deleted hemizygously and unintentionally in PTEN-deleted cancers. Strikingly, in a subset of GBM, SCD was also epigenetically silenced. A combination of SCD deletion and methylation resulted in two molecular subgroups – one that expressed SCD, and another that showed little or no detectable SCD. SCD, is an integral membrane protein of the endoplasmic reticulum and converts saturated fatty acids to monounsaturated fatty acids (Oleic and palmitoleic acids) that are critical for membrane fluidity and function, and thus SCD is generally overexpressed in most cancers. We show that SCD expressing lines are highly sensitive to multiple SCD inhibitors, while non-expressors are resistant. Despite modest BBB penetration, one SCD inhibitor was remarkably efficient in blocking intracranial tumor growth. SCD is an oxygen-dependent enzyme. We show that SCD retains significant enzymatic activity even in highly hypoxic conditions. Finally, through RNAseq, functional proteomics and ATACseq, we demonstrate an evolutionarily conserved mechanism of acquired resistance to SCD inhibitor through drug-induced acute phase signaling response in multiple SCD expressing cancers.

Differential Effects of Dietary Fatty Acids on Body Composition and Adiposity

2020 ◽  
Vol 16 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Hadi Emamat ◽  
Zahra Yari ◽  
Hossein Farhadnejad ◽  
Parvin Mirmiran
Keyword(s):  
Fatty Acids ◽  
Body Composition ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Total Body Weight ◽  
Fat Distribution ◽  
Monounsaturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Dietary Fats ◽  
Total Body

Recent evidence has highlighted that fat accumulation, particularly abdominal fat distribution, is strongly associated with metabolic disturbance. It is also well-recognized that the metabolic responses to variations in macronutrients intake can affect body composition. Previous studies suggest that the quality of dietary fats can be considered as the main determinant of body-fat deposition, fat distribution, and body composition without altering the total body weight; however, the effects of dietary fats on body composition have controversial results. There is substantial evidence to suggest that saturated fatty acids are more obesogen than unsaturated fatty acids, and with the exception of some isomers like conjugate linoleic acid, most dietary trans fatty acids are adiposity enhancers, but there is no consensus on it yet. On the other hand, there is little evidence to indicate that higher intake of the n-3 and the n-6 polyunsaturated fatty acids can be beneficial in attenuating adiposity, and the effect of monounsaturated fatty acids on body composition is contradictory. Accordingly, the content of this review summarizes the current body of knowledge on the potential effects of the different types of dietary fatty acids on body composition and adiposity. It also refers to the putative mechanisms underlying this association and reflects on the controversy of this topic.

scholarly journals Polyunsaturated ω-3 fatty acids inhibit ACE2-controlled SARS-CoV-2 binding and cellular entry

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Goc ◽  
Aleksandra Niedzwiecki ◽  
Matthias Rath
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Eicosapentaenoic Acid ◽  
Linolenic Acid ◽  
Cathepsin L ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
In Vivo Experiments ◽  
Lipid Compounds

AbstractThe strain SARS-CoV-2, newly emerged in late 2019, has been identified as the cause of COVID-19 and the pandemic declared by WHO in early 2020. Although lipids have been shown to possess antiviral efficacy, little is currently known about lipid compounds with anti-SARS-CoV-2 binding and entry properties. To address this issue, we screened, overall, 17 polyunsaturated fatty acids, monounsaturated fatty acids and saturated fatty acids, as wells as lipid-soluble vitamins. In performing target-based ligand screening utilizing the RBD-SARS-CoV-2 sequence, we observed that polyunsaturated fatty acids most effectively interfere with binding to hACE2, the receptor for SARS-CoV-2. Using a spike protein pseudo-virus, we also found that linolenic acid and eicosapentaenoic acid significantly block the entry of SARS-CoV-2. In addition, eicosapentaenoic acid showed higher efficacy than linolenic acid in reducing activity of TMPRSS2 and cathepsin L proteases, but neither of the fatty acids affected their expression at the protein level. Also, neither reduction of hACE2 activity nor binding to the hACE2 receptor upon treatment with these two fatty acids was observed. Although further in vivo experiments are warranted to validate the current findings, our study provides a new insight into the role of lipids as antiviral compounds against the SARS-CoV-2 strain.

scholarly journals Differential Deleterious Impact of Highly Saturated Versus Monounsaturated Fat Intake on Vascular Function, Structure, and Mechanics in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 1003
Author(s):  
Elena Vega-Martín ◽  
Marta Gil-Ortega ◽  
Raquel González-Blázquez ◽  
Sara Benedito ◽  
Jesús Fernández-Felipe ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arterial Stiffness ◽  
Thoracic Aorta ◽  
Vascular Function ◽  
Saturated Fatty Acids ◽  
Vascular Wall ◽  
Monounsaturated Fatty Acids ◽  
Mesenteric Arteries ◽  
Monounsaturated Fat ◽  
The Impact

Vegetable oils such as palm oil (enriched in saturated fatty acids, SFA) and high-oleic-acid sunflower oil (HOSO, containing mainly monounsaturated fatty acids, MUFA) have emerged as the most common replacements for trans-fats in the food industry. The aim of this study is to analyze the impact of SFA and MUFA-enriched high-fat (HF) diets on endothelial function, vascular remodeling, and arterial stiffness compared to commercial HF diets. Five-week-old male C57BL6J mice were fed a standard (SD), a HF diet enriched with SFA (saturated oil-enriched Food, SOLF), a HF diet enriched with MUFA (unsaturated oil-enriched Food, UOLF), or a commercial HF diet for 8 weeks. Vascular function was analyzed in the thoracic aorta. Structural and mechanical parameters were assessed in mesenteric arteries by pressure myography. SOLF, UOLF, and HF diet reduced contractile responses to phenylephrine and induced endothelial dysfunction in the thoracic aorta. A significant increase in the β-index, and thus in arterial stiffness, was also detected in mesenteric arteries from the three HF groups, due to enhanced deposition of collagen in the vascular wall. SOLF also induced hypotrophic inward remodeling. In conclusion, these data demonstrate a deleterious effect of HF feeding on obesity-related vascular alterations that is exacerbated by SFA.

scholarly journals Bioactive Lipids of Seaweeds from the Portuguese North Coast: Health Benefits versus Potential Contamination

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1366
Author(s):  
Cristina Soares ◽  
Sara Sousa ◽  
Susana Machado ◽  
Elsa Vieira ◽  
Ana P. Carvalho ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Fatty Acid Content ◽  
Total Lipid Content ◽  
Monounsaturated Fatty Acids ◽  
North Coast ◽  
Bioactive Lipids ◽  
The North ◽  
Atherogenicity Index ◽  
Polycyclic Aromatic

The total lipid content and lipidic profile of seaweeds harvested in the North Coast and purchased in Portugal were determined in this paper. The amount of total lipids in the different species of seaweeds varied between 0.7 ± 0.1% (Chondrus crispus) and 3.8 ± 0.6% (Ulva spp.). Regarding the fatty acid content, polyunsaturated fatty acids (PUFA) ranged between 0–35%, with Ulva spp. presenting the highest amount; monounsaturated fatty acids (MUFA) varied between 19 and 67%; and saturated fatty acids (SFA) were predominant in C. crispus (45–78%) and Gracilaria spp. (36–79%). Concerning the nutritional indices, the atherogenicity index (AI) was between 0.4–3.2, the thrombogenicity index (TI) ranged from 0.04 to 1.95, except for Gracilaria spp., which had a TI of 7.6, and the hypocholesterolemic/hypercholesterolemic ratio (HH) values ranged between 0.88–4.21, except for Gracilaria spp., which exhibited values between 0.22–9.26. The n6/n3 ratio was below 1 for most of the species evaluated, except for Ascophyllum nodosum, which presented a higher value, although below 2. Considering the PUFA/SFA ratio, seaweeds presented values between 0.11–1.02. The polycyclic aromatic hydrocarbons (PAHs) and aliphatic hydrocarbons (AHCs) contamination of seaweeds under study was also quantified, the values found being much lower than the maximum levels recommended for foodstuff.

scholarly journals Effects of polyunsaturated fatty acids in diets fed to sows on fatty acids in brain, muscle and skin of their piglets

2020 ◽  
Vol 50 (1) ◽  
pp. 47-54
Author(s):  
I De Gasperín ◽  
J.G. Vicente ◽  
J.M. Pinos-Rodríguez ◽  
F Montiel ◽  
R Loeza ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Soybean Oil ◽  
Fatty Acid Profile ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Fatty Acid Profiles ◽  
Polyunsaturated Fat ◽  
Pork Lard ◽  
Piglet Survival

The aim of this research was to determine fatty acid profiles in piglet brain, skin, and muscle, and in the milk of sows fed fat with different saturation grades during gestation and lactation. At 42 days of gestation, 50 multiparous sows were randomly allocated to one of two treatments, namely a diet containing pork lard (n = 25) and a diet containing soybean oil (n = 25). The fats were provided at 3.6% during gestation and at 4% during lactation. The experimental diets were offered through the weaning of the piglets. The fatty acid profile of the milk was determined fourteen days after parturition. At weaning (21 days postpartum) and seven days later, one of the piglets (n = 64) from 16 sows allocated to each treatment was selected at random to determine fatty acid profiles in brain, skin and muscle. Saturated and monounsaturated fatty acids were higher in the diet with pork lard than in that with soybean oil, in which the polyunsaturated fat content was higher. A higher saturation of fatty acids was found in milk from the sows that consumed pork lard, which contained more saturated fatty acids than the milk from sows that consumed soybean oil. The fatty acid profiles in muscle and skin of the piglets were affected by the diet of the sows. However, the fatty acid profile of the piglets’ brains was not affected by the diet of their mothers. Keywords: fat saturation, lard, piglet survival, sow feeding, soybean oil

Composition and Nutritional Evaluation of the Cuttlefish Muscle

2012 ◽  
Vol 554-556 ◽  
pp. 1553-1558
Author(s):  
Sheng Jun Chen ◽  
Lai Hao Li ◽  
Xian Qing Yang ◽  
Bo Qi ◽  
Yan Yan Wu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Crude Protein ◽  
Nutritive Value ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Essential Amino Acids ◽  
Nutritive Quality ◽  
High Quality Protein ◽  
Acid Index

The nutritional components in the cuttlefish muscle were analyzed and the nutritive quality was evaluated in the paper. The results showed that the contents of the cuttlefish muscle in crude protein, crude fat, carbohydrate were 16.60%, 0.86%, 1.30%, respectively. There were 18 kinds amino acids and the total amino acids reached 17.44%, with an essential amino acid index(EAAI) of 67.95. The composition of the essential amino acids in muscle ratio was consistent with the FAO/WHO standards. In addition, the contents of saturated fatty acids, monounsaturated fatty acids and polyunsaturated fatty acids were 41.13%, 12.15% and 46.72%, respectively. And the muscle contains a higher content of EPA and DHA, reached 11.0% and 24.49%, respectively. It was considered that the cuttlefish muscle has a high nutritive value and it can be the important material of the high quality protein and unsaturated fatty acid.

scholarly journals Manipulation of the fatty acids composition of poultry meat and giblets by dietary inclusion of two oil sources and conjugated linoleic acid

2008 ◽  
Vol 60 (6) ◽  
pp. 1388-1398 ◽  
Author(s):  
S.F. Zanini ◽  
E. Vicente ◽  
G.L. Colnago ◽  
B.M.S. Pessotti ◽  
M.A. Silva
Keyword(s):  
Fatty Acids ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Canola Oil ◽  
Broiler Chickens ◽  
Saturated Fatty Acids ◽  
Saturated Fat ◽  
Monounsaturated Fatty Acids ◽  
Poultry Meat ◽  
Breast Meat

The effect of dietary conjugated linoleic acid (CLA) in association with two vegetable oil sources on the fatty acids of meat and giblets of broiler chickens was evaluated. Two hundred 21-day-old broiler chickens were distributed in a completely randomized factorial design 2 x 5 (two oil sources, soybean or canola oil; and five levels of CLA, 0.0, 2.5, 5.0, 7.5, and 10.0g/kg). The addition of CLA to the diet resulted in an increase (P<0.05) in CLA deposition in the analyzed tissues. CLA supplementation also reduced (P<0.05) the rate of polyunsaturated to saturated fatty acids in thigh, breast, heart, and gizzard. There was interaction of CLA x oil source (P<0.05). The intake of soybean oil, associated with increasing CLA, resulted in an increase in lipid deposition in edible portions as observed by an increase in the overall content of fatty acids, including CLA, while the use of canola oil, associated with increasing CLA in the diet, resulted in a decrease in lipid content in edible portions, specifically regarding that of saturated fat (P<0.05) in breast meat and liver and in the content of monounsaturated fatty acids (P<0.05) in thigh, breast, liver, and gizzard.

Genetic variation in fatty acid composition of subcutaneous fat in cattle

2013 ◽  
Vol 53 (2) ◽  
pp. 129 ◽  
Author(s):  
M. J. Kelly ◽  
R. K. Tume ◽  
S. Newman ◽  
J. M. Thompson
Keyword(s):  
Fatty Acids ◽  
Genetic Variation ◽  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Saturated Fatty Acids ◽  
Genetic Correlations ◽  
Subcutaneous Fat ◽  
Monounsaturated Fatty Acids ◽  
Selection For

Genetic parameters were estimated for fatty acid composition of subcutaneous beef fat of 1573 animals which were the progeny of 157 sires across seven breeds grown out on pasture and then finished on either grain or grass in northern New South Wales or in central Queensland. There was genetic variation in individual fatty acids with estimates of heritability for the proportions of C14 : 0, C14 : 1c9, C16 : 0, C16 : 1c9, C18 : 0 and C18 : 1c9 fatty acids in subcutaneous beef fat of the order of 0.4 or above. Also substantial correlations between some fatty acids were observed. Genetic correlations between fatty acids and fat depth at the P8 site suggested that much of the genetic variation in fatty acid composition was related to changes in fatness. Selection for decreased fatness resulted in decreased proportions of C18 : 1c9 with concomitant increases in C18 : 0, C14 : 0 and C16 : 0. This suggested that selection for decreased fatness at a given weight will result in a decrease in the proportions of monounsaturated fatty acids in the subcutaneous fat in the carcass with a corresponding increase in the proportions of saturated fatty acids.

scholarly journals Study on the Profile of Fatty Acids of Broiler Chicken Raised and Slaughtered in Industrial System

2019 ◽  
Vol 70 (11) ◽  
pp. 4089-4094
Author(s):  
Marius Mihai Ciobanu ◽  
Paul Corneliu Boisteanu ◽  
Daniel Simeanu ◽  
Alina Narcisa Postolache ◽  
Roxana Lazar ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fatty Acid Profile ◽  
Broiler Chicken ◽  
Saturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Industrial System ◽  
Nutritional Indices ◽  
Total Lipids ◽  
Different Levels

Fatty acid profile and the related nutritional indices of the breast, thigh and drumstick muscles were studied at three farms, suppliers of ROSS 308 line of broilers, slaughtered at the age of 42 days. The proximate chemical composition of the commercial slaughter cuts revealed contents between 16.26�22.78% for proteins and 1.80�7.45% for total lipids, the breast having the highest protein and ash content and lowest values for fat and moisture. The obtained values were mainly affected by region (P[0.001). Meat fatty acid profile was affected (P[0.001) by commercial slaughter regions (CSR) and by the interactions between CSR and supplier farms (Farm A, B, and C) at different levels. The obvious findings highlighted that Farm B supplied broilers with a delivered higher content of beneficial fatty acids (LA, LNA, AA, EPA, and DHA) in breasts and drumstick, while for thigh, Farm C had the best results. The content of total saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (MUFAs) had the highest level in the thigh (P[0.001).

Sign in / Sign up

Export Citation Format

Share Document