scholarly journals Effect of n-3 and n-6 Polyunsaturated Fatty Acids on Microsomal P450 Steroidogenic Enzyme Activities and In Vitro Cortisol Production in Adrenal Tissue From Yorkshire Boars

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1512-1521 ◽  
Author(s):  
Xuemei Xie ◽  
Xudong Wang ◽  
Gail J. Mick ◽  
Janusz H. Kabarowski ◽  
Landon Shay Wilson ◽  
...  

AbstractDysregulation of adrenal glucocorticoid production is increasingly recognized to play a supportive role in the metabolic syndrome although the mechanism is ill defined. The adrenal cytochrome P450 (CYP) enzymes, CYP17 and CYP21, are essential for glucocorticoid synthesis. The omega-3 and omega-6 polyunsaturated fatty acids (PUFA) may ameliorate metabolic syndrome, but it is unknown whether they have direct actions on adrenal CYP steroidogenic enzymes. The aim of this study was to determine whether PUFA modify adrenal glucocorticoid synthesis using isolated porcine microsomes. The enzyme activities of CYP17, CYP21, 11β-hydroxysteroid dehydrogenase type 1, hexose-6-phosphate dehydrogenase (H6PDH), and CYP2E1 were measured in intact microsomes treated with fatty acids of disparate saturated bonds. Cortisol production was measured in a cell-free in vitro model. Microsomal lipid composition after arachidonic acid (AA) exposure was determined by sequential window acquisition of all theoretical spectra-mass spectrometry. Results showed that adrenal microsomal CYP21 activity was decreased by docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), eicosapentaenoic acid, α-linolenic acid, AA, and linoleic acid, and CYP17 activity was inhibited by DPA, DHA, eicosapentaenoic acid, and AA. Inhibition was associated with the number of the PUFA double bonds. Similarly, cortisol production in vitro was decreased by DPA, DHA, and AA. Endoplasmic enzymes with intraluminal activity were unaffected by PUFA. In microsomes exposed to AA, the level of AA or oxidative metabolites of AA in the membrane was not altered. In conclusion, these observations suggest that omega-3 and omega-6 PUFA, especially those with 2 or more double bonds (DPA, DHA, and AA), impede adrenal glucocorticoid production.

2014 ◽  
Vol 82 (5) ◽  
pp. 1778-1785 ◽  
Author(s):  
Claude Lachance ◽  
Mariela Segura ◽  
Maria C. Dominguez-Punaro ◽  
Gabriella Wojewodka ◽  
Juan B. De Sanctis ◽  
...  

ABSTRACTStreptococcus suisis an important swine pathogen and an emergent zoonotic pathogen. Excessive inflammation caused byS. suisis responsible for early high mortality in septic shock-like syndrome cases. Polyunsaturated fatty acids (PUFAs) may contribute to regulating inflammatory processes. This study shows that mouse infection byS. suisis accompanied by an increase of arachidonic acid, a proinflammatory omega-6 (ω-6) PUFA, and by a decrease of docosahexaenoic acid, an anti-inflammatory ω-3 PUFA. Macrophages infected withS. suisshowed activation of mitogen-activated protein kinase pathways and cyclooxygenase-2 upregulation. Fenretinide, a synthetic vitamin A analog, reducedin vitroexpression of inflammatory mediators. Pretreatment of mice with fenretinide significantly improved their survival by reducing systemic proinflammatory cytokines during the acute phase of anS. suisinfection. These findings indicate a beneficial effect of fenretinide in diminishing the expression of inflammation and improving survival during an acute infection by a virulentS. suisstrain.


2021 ◽  
Vol 22 (13) ◽  
pp. 6965
Author(s):  
Kamila P. Liput ◽  
Adam Lepczyński ◽  
Magdalena Ogłuszka ◽  
Agata Nawrocka ◽  
Ewa Poławska ◽  
...  

The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n–3 (omega–3) and n–6 (omega–6) to decrease the risk of metabolic disturbances. Consequently, excessive n–6 PUFAs content and high n–6/n–3 ratio are found in Western-type diet. The importance of a dietary n–6/n–3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n–3) and longer-chain n–3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n–3 PUFAs and oxylipins formed from n–6 PUFAs on inflammation. Evidence of PUFAs’ role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.


Author(s):  
Marcia C. de Oliveira Otto ◽  
Jason H. Y. Wu ◽  
Ana Baylin ◽  
Dhananjay Vaidya ◽  
Stephen S. Rich ◽  
...  

1989 ◽  
Vol 256 (4) ◽  
pp. H968-H973 ◽  
Author(s):  
H. Shimokawa ◽  
P. M. Vanhoutte

Dietary supplementation with cod-liver oil significantly augments endothelium-dependent relaxations in porcine coronary arteries. The present study was designed to examine the effect of dietary administration of omega 3 polyunsaturated fatty acids (mainly eicosapentaenoic acid, the major component of fish oil) on endothelium-dependent relaxations in porcine coronary arteries. Male Yorkshire pigs were maintained 4 wk on a regular diet with or without supplementation with purified eicosapentaenoic acid (3.5 g/day) and docosahexaenoic acid (1.5 g/day). Endothelium-dependent relaxations were examined in vitro. In rings from the treated group, endothelium-dependent relaxations were augmented in response to bradykinin, serotonin, and ADP, but not to the calcium ionophore A23187. These augmentations were not altered by indomethacin but were significantly inhibited by methylene blue, an inhibitor of guanylate cyclase. In the treated group, endothelium-dependent relaxations to aggregating platelets also were significantly augmented; platelet-induced contractions of quiescent rings were inhibited more by the presence of the endothelium than in arteries from the control group. Bioassay experiments demonstrated that the release of endothelium-derived relaxing factor(s) by bradykinin and relaxations of the vascular smooth muscle to the factor(s) were greater in arteries from the treated group. These observations indicate that dietary omega 3 polyunsaturated fatty acids augment receptor-operated endothelium-dependent relaxations, partly due to the augmented release of endothelium-derived relaxing factor(s) and partly due to the augmented relaxation of the vascular smooth muscle to the factor(s).


2021 ◽  
Vol 2 (2) ◽  
pp. 12
Author(s):  
Samina Akbar ◽  
Muhammad Zeeshan Bhatti ◽  
Rida Fatima Saeed ◽  
Asma Saleem Qazi

Over the last decades, the polyunsaturated fatty acids (PUFAs) have been largely explored not only for their nutritional value but also for the numerous biological functions and therapeutic effects. The serum and erythrocyte levels of PUFAs depend on the genetic control of metabolism as well as the dietary intake and are considered to reflect the health and disease status of an individual. Two families of PUFAs, omega-3 (n-3) and omega-6 (n-6), have gained much attention because of their involvement in the production of bioactive lipid mediators and therefore, a balanced omega-6/omega-3 ratio is crucial in maintaining the overall health of an individual. Omega-3 PUFAs, notably eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) have been shown to exert beneficial effects, possibly due to their lipid-lowering, anti-inflammatory, anti-hypertensive and cardioprotective effects, whereas omega-6 fatty acids such as arachidonic acid (ARA, 20:4n-6) exhibit the opposite properties. Even though, numerous epidemiological studies and clinical interventions have clearly established the effectiveness of omega-3 PUFAs in various pathological conditions including dyslipidemia, obesity, diabetes, cancer, cardiovascular and neurodegenerative diseases, some controversies do exist about the beneficial effects of omega-3 PUFAs and need to be clarified. Larger clinical trials with extended follow-up periods are required along with a careful dose selection, in order to confirm the clinical significance and efficacy of omega-3 PUFAs as therapeutic agents.


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