Dietary fatty acids and CD36-mediated cholesterol homeostasis: potential mechanisms

2020 ◽  
pp. 1-14 ◽  
Author(s):  
Elif Ulug ◽  
Reyhan Nergiz-Unal

Abstract Currently, the prevention and treatment of CVD have been a global focus since CVD is the number one cause of mortality and morbidity. In the pathogenesis of CVD, it was generally thought that impaired cholesterol homeostasis might be a risk factor. Cholesterol homeostasis is affected by exogenous factors (i.e. diet) and endogenous factors (i.e. certain receptors, enzymes and transcription factors). In this context, the number of studies investigating the potential mechanisms of dietary fatty acids on cholesterol homeostasis have increased in recent years. As well, the cluster of differentiation 36 (CD36) receptor is a multifunctional membrane receptor involved in fatty acid uptake, lipid metabolism, atherothrombosis and inflammation. CD36 is proposed to be a crucial molecule for cholesterol homeostasis in various mechanisms including absorption/reabsorption, synthesis, and transport of cholesterol and bile acids. Moreover, it has been reported that the amount of fatty acids and fatty acid pattern of the diet influence the CD36 level and CD36-mediated cholesterol metabolism principally in the liver, intestine and macrophages. In these processes, CD36-mediated cholesterol and lipoprotein homeostasis might be impaired by dietary SFA and trans-fatty acids, whereas ameliorated by MUFA in the diet. The effects of PUFA on CD36-mediated cholesterol homeostasis are controversial depending on the amount of n-3 PUFA and n-6 PUFA, and the n-3:n-6 PUFA ratio. Thus, since the CD36 receptor is suggested to be a novel nutrient-sensitive biomarker, the role of CD36 and dietary fatty acids in cholesterol metabolism might be considered in medical nutrition therapy in the near future. Therefore, the novel nutritional target of CD36 and interventions that focus on dietary fatty acids and potential mechanisms underlying cholesterol homeostasis are discussed in this review.

1969 ◽  
Vol 23 (2) ◽  
pp. 421-427 ◽  
Author(s):  
G. A. Garton ◽  
W. R. H. Duncan

1. Samples of subcutaneous (inguinal) and perinephric adipose tissue were obtained, at slaughter, from each of twenty male calves. Three were neonatal animals, three were 3 days old and two were fed on reconstituted milk to appetite until they weighed 100 kg. The other twelve calves were given milk until they reached 50 kg live weight; concentrates were then included in the diet until, at 60 kg live weight, six calves were slaughtered. The remaining six calves were raised to 100 kg on concentrates alone. The weight of the empty reticulo-rumen of each slaughtered calf was recorded.2. The component fatty acids of the adipose tissue triglycerides of the neonatal and 3-day-old calves were very similar; about 80% consisted of oleic acid (18:1) and palmitic acid (16:0) and the remainder comprised stearic acid (18:0), palmitoleic acid (16:1) and myristic acid (14:0), together with very small amounts of other acids which, in the glycerides of the 3-day-old calves, included some evidently of colostral origin. The perinephric glycerides of both these groups of calves were somewhat more unsaturated than were those of subcutaneous adipose tissue.3. The continued consumption of milk by the calves slaughtered at 60 kg live weight was reflected in the presence of enhanced proportions of 14:0, 18:2, 17:0 and 17:1 in the depot triglycerides and, in addition, very small amounts of branched-chain acids and trans 18:1 were detected. A similar fatty acid pattern was observed in the triglycerides of the calves which were given milk only until they were 100 kg live weight. In all these calves only limited growth of the rumen took place.4. By contrast, the calves which were raised on solid feed from 60 kg to 100 kg and in which rumen development had taken place had depot triglycerides whose fatty acid composition resembled that found in adult animals. Increased proportions of stearic acid accompanied by relatively large amounts of trans 18:1 were present, evidently as a result of the assimilation of the products of bacterial modification of dietary fatty acids in the rumen.5. Regardless of the age of the calves and the over-all fatty acid composition of their tissue triglycerides, the intramolecular disposition of the fatty acids was similar in that saturated components were present esterified mainly in positions 1 and 3, and unsaturated acids for the most part in position 2; the only major exception to this distribution pattern was in respect of trans 18:1 which, when present, was preferentially esterified to the primary alcoholic groups of the glycerol moiety as if it were a saturated acid.


1989 ◽  
Vol 69 (3) ◽  
pp. 813-817 ◽  
Author(s):  
E. R. FARNWORTH ◽  
J. K. G. KRAMER

Sows were fed a control diet or one with added tallow or soybean oil during gestation. Sow and fetal blood plasma fatty acids were determined at 57, 85 and 110 d gestation. The sow plasma fatty acid pattern, particularly 18:2n-6, was influenced by diet, but showed little change during gestation. High levels of polyunsaturated fatty acids, especially 18:2n-6 and 20:4n-6, were found in sow plasma. Fetal blood fatty acids were not directly influenced by maternal diet, but showed changes as gestation progressed. In the fetal plasma, 20:4n-6 was the major long chain polyunsaturated fatty acid, but in addition, high levels of 22:6n-3 were also found. The percent n-6 fatty acids were in higher concentrations than the n-3 fatty acids in both maternal and fetal plasma. Key words: Fetus, blood, fatty acids, swine


2021 ◽  
Author(s):  
Yi Fan ◽  
Yu Qiu ◽  
Qing Chen ◽  
Sijie Wang ◽  
Mingming Xu ◽  
...  

Abstract ObjectiveTo investigate the relationship between dietary fatty acid pattern and the risk of oral cancer (OC).MethodIn 446 patients with primary oral cancer and 448 controls, we assessed prediagnosis consumption of 159 food items by food frequency questionnaires completed within 1 week of diagnosis. Fatty acid patterns were identified using principal component analysis. Odds ratio (OR) and 95% confidence (CI) interval was calculated.ResultsGeneral differences of fatty acid intake were observed between case and control, intake of saturated fatty acids such as C14:0, C16:0, C18:0 are higher in case than control group (p < 0.001), intake of monounsaturated fatty acid such as C18:1 is higher in case than control group (p < 0.001). We identified a fatty acid pattern which was characterized by saturated fatty acids and it explained 33.2% of the overall variability of the 32 fatty acids. The identified fatty acid pattern scores were positively associated with a higher risk of oral cancer [multivariable-adjusted OR comparing extreme quintiles, 3.325 (95%CI: 2.222, 4.975); Ptrend<0.001].ConclusionsGeneral differences of dietary fatty acids were observed between oral cancer patients and controls. A dietary fatty acids pattern, which was mainly composed of saturated fatty acids were positively correlated with the risk of oral cancer.


1997 ◽  
Vol 77 (5) ◽  
pp. 805-823 ◽  
Author(s):  
Nicola M. Jeffery ◽  
Mario Cortina ◽  
Eric A. Newsholme ◽  
Philip C. Calder

To obtain further information about the immunomodulatory effects of specific dietary fatty acids, weanling male rats were fed for 6 weeks on high-fat (178 g/kg) diets which differed according to the principal fatty acids present. The nine diets used differed in their contents of palmitic, oleic, linoleic and α-linolenic acids; as a result the total polyunsaturated fatty acid (PUFA) content and the PUFA: saturated fatty acid ratio varied (from 17·8 to 58·5 g/lW g fatty acids and from 0·28 to 5·56 respectively). The n−6 PUFA: n−3 PUFA ratio was kept constant in all diets at approximately 7·0.The fatty acid compositions of the serum and of spleen lymphocytes were significantly influenced by that of the diet fed. The ex vivo proliferation of spleen lymphocytes decreased as the levelof oleic acid in the diet increased. Spleen natural killer cell activity decreased as the oleic acid content of the diet increased and increased as the palmitic acid content of the diet increased. The extent of the effects of these fatty acids on lymphocyte functions was modified by the nature of the background fatty acid composition of the diet.


1998 ◽  
Vol 80 (6) ◽  
pp. 495-502 ◽  
Author(s):  
Barbara A. Fielding ◽  
Keith N. Frayn

Lipoprotein lipase (EC 3.1.1.34; LPL) is a key enzyme regulating the disposal of lipid fuels in the body. It is expressed in a number of peripheral tissues including adipose tissue, skeletal and cardiac muscle and mammary gland. Its role is to hydrolyse triacylglycerol (TG) circulating in the TG-rich lipoprotein particles in order to deliver fatty acids to the tissue. It appears to act preferentially on chylomicron-TG, and therefore may play a particularly important role in regulating the disposition of dietary fatty acids. LPL activity is regulated according to nutritional state in a tissue-specific manner according to the needs of the tissue for fatty acids. For instance, it is highly active in lactating mammary gland; in white adipose tissue it is activated in the fed state and suppressed during fasting, whereas the reverse is true in muscle. Such observations have led to the view of LPL as a metabolic gatekeeper, especially for dietary fatty acids. However, closer inspection of its action in white adipose tissue reveals that this picture is only partially true. Normal fat deposition in adipose tissue can occur in the complete absence of LPL, and conversely, if LPL activity is increased by pharmacological means, increased fat storage does not necessarily follow. LPL appears to act as one member of a series of metabolic steps which are regulated in a highly coordinated manner. In white adipose tissue, it is clear that there is a major locus of control of fatty acid disposition downstream from LPL. This involves regulation of the pathway of fatty acid uptake and esterification, and appears to be regulated by a number of factors including insulin, acylation-stimulating protein and possibly leptin.


2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1038-1038
Author(s):  
Michael Miklus ◽  
Pedro Prieto ◽  
Cynthia Barber ◽  
Robert Rhoads ◽  
Samer El-Kadi

Abstract Objectives The objectives of this study were to determine the effect of 2’fucosyllactose (2’FL) and fat blends on growth, body composition and fatty acid profile of the liver and brain using the neonatal pig as a model for the human infant. Methods Pigs (3 d old) were randomly assigned to either: 1. control, 2. Palm Olein (PO) fat blend – Low 2'-FL, 3. PO – High 2'-FL, 4. High oleic acid (HO) – Low 2'-FL, 5. HO FB – High 2'-FL, 6. PO FB – GLA, or 7. kept with their sows. Pigs in groups 1 to 6 received 250 ml·kg−1·d−1 of formula in 5 equal meals for 15 d. On day 14 of the study, groups 1–6 received intraperitoneal E. coli LPS challenge at 100 µg·kg−1 weight. Results Body weight was greater for piglets fed by sows than those in the other groups (P &lt; 0.001). In addition, % fat and bone mineral content were higher in the sow-fed group while lean % was less sow-fed piglets (group 7) compared with those in the other groups (P &lt; 0.05). Only longissimus weight expressed as a % of body weight, was greater for group 7 compared with all other groups (P &lt; 0.001). Soleus, semitendinosus, brain, heart and spleen weights as a % of body weight were similar across all groups. However, liver weight as a % of body weight was greater in groups 1–6 (3.7%) compared with group 7 (2.8%; P &lt; 0.001). The proportion of brain 16:1 fatty acid was less (0.83%) for groups 1–6 than for group 7 pigs (1.08%; P &lt; 0.0001). The proportion of 20:3 N6 was greatest (0.66%) for group 3 compared with groups 1 and 4 (0.55%; P &lt; 0.05). In addition, the proportion of 20:5 N3 was greatest (0.12%) for group 3 compared with groups 1 and 7 (0.07%; P &lt; 0.05). The proportion of liver 16:1, 18:0, and 18:1 cis-11 fatty acids were greater for group 7 (2.3, 23, 2.2%) than groups 1–6 (0.2, 20, 1.2%; P &lt; 0.0001). Conversely, the contribution of 14:0, 18:1 cis-9, 18:3 N6 cis-6,9,12, and 22:6 N3 were greater for pigs in groups 1–6 (1.3, 0.6, and 14, 7.8%) compared with those in group 7 (0.5, 8.5, 0.2 and 3.5%; P &lt; 0.0001). Conclusions Our data suggest that feeding 2’fucosyllactose had no effect on the body weight gain and composition in neonatal pigs. Our data also suggest that dietary fatty acids have a greater effect on liver than on brain fatty acid composition. Funding Sources Funding for the work was provided by Perrigo Nutritionals, LLC.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 722 ◽  
Author(s):  
Zhibo Gai ◽  
Tianqi Wang ◽  
Michele Visentin ◽  
Gerd Kullak-Ublick ◽  
Xianjun Fu ◽  
...  

Obesity and hyperlipidemia are the most prevalent independent risk factors of chronic kidney disease (CKD), suggesting that lipid accumulation in the renal parenchyma is detrimental to renal function. Non-esterified fatty acids (also known as free fatty acids, FFA) are especially harmful to the kidneys. A concerted, increased FFA uptake due to high fat diets, overexpression of fatty acid uptake systems such as the CD36 scavenger receptor and the fatty acid transport proteins, and a reduced β-oxidation rate underlie the intracellular lipid accumulation in non-adipose tissues. FFAs in excess can damage podocytes, proximal tubular epithelial cells and the tubulointerstitial tissue through various mechanisms, in particular by boosting the production of reactive oxygen species (ROS) and lipid peroxidation, promoting mitochondrial damage and tissue inflammation, which result in glomerular and tubular lesions. Not all lipids are bad for the kidneys: polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to help lag the progression of chronic kidney disease (CKD). Lifestyle interventions, especially dietary adjustments, and lipid-lowering drugs can contribute to improve the clinical outcome of patients with CKD.


1991 ◽  
Vol 10 (3) ◽  
pp. 325-340 ◽  
Author(s):  
D. R. Webb ◽  
R. A. Sanders

Caprenin (CAP) is a triglyceride that primarily contains caprylic (C8:0), capric (C10:0), and behenic (C22:0) acids. This study was undertaken to determine whether or not CAP is qualitatively digested, absorbed, and rearranged like other dietary fats and oils that contain these medium-chain and very long-chain fatty acids. In vitro results showed that neat CAP, coconut oil (CO) and peanut oil (PO) were hydrolyzed by porcine pancreatic lipase. All of the neat triglycerides also were digested in vivo by both male and female rats. This was shown by the recovery of significantly more extractable lymphatic fat than with fat-free control animals and by the recovery of orally administered triglyceride-derived fatty acids in lymph triglycerides. However, substantially more PO (74%) and CO (51%) were recovered in lymph relative to CAP (10%). These quantitative differences are consistent with the fatty acid composition of each triglyceride and primary routes of fatty acid uptake. The 24-h lymphatic recovery of CAP-derived C8:0, C10:0, and C22:0 averaged 3.9%, 17.8%, and 11.2%, respectively, for male and female rats. The C8:0 and C10:0 results approximated those obtained with CO (2.0% and 16.3%, respectively). In contrast, the 24-h absorbability of C22:0 in CAP was significantly less than that seen in PO (55.4%). Finally, there was no evidence of significant rearrangement of the positions of fatty acids on glycerol during digestion and absorption. Those fatty acids recovered in lymphatic fat tended to occupy the same glyceride positions that they did in the neat administered oils. However, the lymph fats recovered from all animals dosed with fat emulsions were enriched with endogenous lymph fatty acids. It is concluded that CAP is qualitatively digested, absorbed, and processed like any dietary fat or oil that contains medium-chain and very long-chain fatty acids.


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