Cholesterol and saturated fatty acids synergistically promote the malignant progression of prostate cancer

De novo lipogenesis (DNL) is now considered as a hallmark of cancer. The overexpression of key enzymes of DNL is characteristic of both primary and advanced disease and may play an important role in resistance to therapies. Here, we showed that DNL is highly enhanced in castrate resistant prostate cancer (CRPC) cells compared to hormone sensitive and enzalutamide resistant cells. This observation suggests that this pathway plays an important role in the initiation of aggressive prostate cancer and in the development of enzalutamide resistance. Importantly, here we show that both prostate cancer cells sensitive and resistant to enzalutamide are dependent on DNL to proliferate. We next combined enzalutamide with an inhibitor of Stearoyl CoA Desaturase 1 (SCD1), an important enzyme in DNL, and observed significantly reduced tumor growth caused by the important change in tumoral lipid desaturation. Our findings suggest that the equilibrium between monounsaturated fatty acids and saturated fatty acids is essential in the establishment of the more aggressive prostate cancer phenotype and that the combination therapy induces a disruption of this equilibrium leading to an important decrease of cell proliferation. These findings provide new insights into the role of DNL in the progression of prostate cancer cells. The study also provides the rationale for the use of an inhibitor of SCD1 in combination with enzalutamide to improve response, delay enzalutamide resistance and improve disease free progression.

Download Full-text

Dietary Changes in Fasting Levels of Factor VII Coagulant Activity (FVII: C) Are Accompanied by Changes in Factor VII Protein and other Vitamin K-dependent Proteins

Thrombosis and Haemostasis ◽

10.1055/s-0038-1653757 ◽

1995 ◽

Vol 73 (02) ◽

pp. 239-242 ◽

Cited By ~ 27

Author(s):

E M Bladbjerg ◽

T Tholstrup ◽

P Marckmann ◽

B Sandström ◽

J Jespersen

Keyword(s):

Fatty Acids ◽

Vitamin K ◽

Protein C ◽

Saturated Fatty Acids ◽

Factor Vii ◽

Dietary Regimen ◽

Blood Samples ◽

Dietary Changes ◽

Coagulant Activity ◽

Before And After

SummaryThe mechanisms behind dietary effects on fasting coagulant activity of factor VII (FVII: C) are not clarified. In the present study of 15 young volunteers, two experimental diets differing in composition of saturated fatty acids (C18:0 [diet S] or C12:0 + C14:0 [diet ML]) were served for 3 weeks each. Fasting blood samples were collected before and after the dietary regimen and analysed for triglycerides, FVII:C, and protein concentrations of FVII, FII, FX, protein C, CRP, albumin, fibrinogen, and F1+2. FVII:C was significantly reduced on diet S compared with diet ML. This was accompanied by a decrease in FVII protein, F1+2 and the vitamin K-dependent proteins FII, FX, and protein C. In contrast, no changes were observed in triglycerides, FVII:C/FVII: Ag, albumin and CRP. Fibrinogen was increased on diet S compared with diet ML. Our findings suggest that the change in fasting FVII:C was part of a general change in concentrations of vitamin K-dependent proteins.

Download Full-text

Platelet Aggregation in Finnish Men and Its Relation to Fatty Acids in Platelets, Plasma and Adipose Tissue

Thrombosis and Haemostasis ◽

10.1055/s-0038-1660071 ◽

1985 ◽

Vol 54 (03) ◽

pp. 563-569 ◽

Cited By ~ 19

Author(s):

M K Salo ◽

E Vartiainen ◽

P Puska ◽

T Nikkari

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Fatty Acid Composition ◽

Fatty Acid ◽

Platelet Aggregation ◽

Acid Composition ◽

Saturated Fatty Acids ◽

Free Living ◽

Ω3 Fatty Acids ◽

Induced Aggregation

SummaryPlatelet aggregation and its relation to fatty acid composition of platelets, plasma and adipose tissue was determined in 196 randomly selected, free-living, 40-49-year-old men in two regions of Finland (east and southwest) with a nearly twofold difference in the IHD rate.There were no significant east-southwest differences in platelet aggregation induced with ADP, thrombin or epinephrine. ADP-induced platelet secondary aggregation showed significant negative associations with all C20-C22 ω3-fatty acids in platelets (r = -0.26 - -0.40) and with the platelet 20: 5ω3/20: 4ω 6 and ω3/ ω6 ratios, but significant positive correlations with the contents of 18:2 in adipose tissue (r = 0.20) and plasma triglycerides (TG) (r = 0.29). Epinephrine-induced aggregation correlated negatively with 20: 5ω 3 in plasma cholesteryl esters (CE) (r = -0.23) and TG (r = -0.29), and positively with the total percentage of saturated fatty acids in platelets (r = 0.33), but had no significant correlations with any of the ω6-fatty acids. Thrombin-induced aggregation correlated negatively with the ω3/6ω ratio in adipose tissue (r = -0.25) and the 20: 3ω6/20: 4ω 6 ratio in plasma CE (r = -0.27) and free fatty acids (FFA) (r = -0.23), and positively with adipose tissue 18:2 (r = 0.23) and 20:4ω6 (r = 0.22) in plasma phospholipids (PL).The percentages of prostanoid precursors in platelet lipids, i. e. 20: 3ω 6, 20: 4ω 6 and 20 :5ω 3, correlated best with the same fatty acids in plasma CE (r = 0.32 - 0.77) and PL (r = 0.28 - 0.74). Platelet 20: 5ω 3 had highly significant negative correlations with the percentage of 18:2 in adipose tissue and all plasma lipid fractions (r = -0.35 - -0.44).These results suggest that, among a free-living population, relatively small changes in the fatty acid composition of plasma and platelets may be reflected in significant differences in platelet aggregation, and that an increase in linoleate-rich vegetable fat in the diet may not affect platelet function favourably unless it is accompanied by an adequate supply of ω3 fatty acids.

Download Full-text

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

Grain Products and Mixed Fodder’s ◽

10.15673/gpmf.v20i2.1764 ◽

2020 ◽

Vol 20 (2) ◽

pp. 38-40

Author(s):

A. Levitsky ◽

A. Lapinska ◽

I. Selivanskaya

Keyword(s):

Fatty Acids ◽

Experimental Model ◽

Unsaturated Fatty Acids ◽

Saturated Fatty Acids ◽

Coconut Oil ◽

The Body ◽

Regulatory Function ◽

Omega 3 ◽

White Rats ◽

Arachidonic Acids

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

Download Full-text

Nutritional aspects and their influences on the pathophysiology of

Revista de Ciências Médicas ◽

10.24220/2318-0897v23n1a2413 ◽

2014 ◽

Vol 23 (1) ◽

pp. 33

Author(s):

Nathalia Liberato Nascimento ◽

Iwyson Henrique Fernandes da Costa ◽

Rivelilson Mendes de Freitas

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Fatty Acids ◽

Folic Acid ◽

Saturated Fatty Acids ◽

Free Radical Scavengers ◽

Radical Scavengers ◽

High Intake ◽

Neuroprotective Effects ◽

Nutritional Factors

The objective of this study was to conduct a review about the nutritional aspects and their influences on the pathophysiology of Alzheimer’s disease. The review describes the pathophysiology of Alzheimer’s disease, the generally indicated diets, and the nutritional factors that may aggravate the disease based on a literature review using the following keywords in English and Portuguese: “Alzheimer’s disease”, “physiopathology”, “nutritional aspects”, and “antioxidants”. A total of 100 articles were found, 48 in Lilacs and 52 in MedLine, but only 54 articles were selected for the review. The use of antioxidants as free radical scavengers is generally indicated in diets for Alzheimer’s patients. Studies also suggest that caffeine, vitamin B12, and folic acid have neuroprotective effects. Cohort studies found that a high intake of saturated fatty acids and obesity increase the risk of Alzheimer’s disease. People with Alzheimer’s disease should avoid diets high in carbohydrates and saturated fats, and prefer foods high in antioxidants.Keywords: Alzheimer disease; Antioxidants; Neurophysiology; Review literture as topic.

Download Full-text

EFFECT OF GINGER, LEMURU FISH OIL SAPONIFICATION AND OLIVE OIL ON COMPOSITION FATTY ACID OF BEEF

Jurnal Agroindustri ◽

10.31186/j.agroind.4.1.31-39 ◽

2014 ◽

Vol 4 (1) ◽

pp. 31-39

Author(s):

Siwitri Kadarsih

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Fish Oil ◽

Olive Oil ◽

Rice Bran ◽

Dry Matter ◽

Unsaturated Fatty Acids ◽

Saturated Fatty Acids ◽

Omega 3 ◽

Omega 6

The objective was to get beef that contain unsaturated fatty acids (especially omega 3 and 6), so as to improve intelligence, physical health for those who consume. The study design using CRD with 3 treatments, each treatment used 4 Bali cattle aged approximately 1.5 years. Observations were made 8 weeks. Pasta mixed with ginger provided konsentrat. P1 (control); P2 (6% saponification lemuru fish oil, olive oil 1%; rice bran: 37.30%; corn: 62.70%; KLK: 7%, ginger paste: 100 g); P3 (lemuru fish oil saponification 8%, 2% olive oil; rice bran; 37.30; corn: 62.70%; KLK: 7%, ginger paste: 200 g). Konsentrat given in the morning as much as 1% of the weight of the cattle based on dry matter, while the grass given a minimum of 10% of the weight of livestock observation variables include: fatty acid composition of meat. Data the analyzies qualitative. The results of the study showed that the composition of saturated fatty acids in meat decreased and an increase in unsaturated fatty acids, namely linoleic acid (omega 6) and linolenic acid (omega 3), and deikosapenta deikosaheksa acid.Keywords :

Download Full-text