scholarly journals Sterculic Acid: The Mechanisms of Action beyond Stearoyl-CoA Desaturase Inhibition and Therapeutic Opportunities in Human Diseases

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 140 ◽  
Author(s):  
Rafael Peláez ◽  
Ana Pariente ◽  
Álvaro Pérez-Sala ◽  
Ignacio M. Larráyoz

In many tissues, stearoyl-CoA desaturase 1 (SCD1) catalyzes the biosynthesis of monounsaturated fatty acids (MUFAS), (i.e., palmitoleate and oleate) from their saturated fatty acid (SFA) precursors (i.e., palmitate and stearate), influencing cellular membrane physiology and signaling, leading to broad effects on human physiology. In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment for various diseases, such as nonalcoholic steatohepatitis, Alzheimer’s disease, cancer, and skin disorders. Sterculic acid (SA) is a cyclopropene fatty acid originally found in the seeds of the plant Sterculia foetida with numerous biological activities. On the one hand, its ability to inhibit stearoyl-CoA desaturase (SCD) allows its use as a coadjuvant of several pathologies where this enzyme has been associated. On the other hand, additional effects independently of its SCD inhibitory properties, involve anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD). This review aims to summarize the mechanisms by which SA exerts its actions and to highlight the emerging areas where this natural compound may be of help for the development of new therapies for human diseases.

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1187
Author(s):  
Ana Pariente ◽  
Álvaro Pérez-Sala ◽  
Rodrigo Ochoa ◽  
Rafael Peláez ◽  
Ignacio M. Larráyoz

In addition to its predominant role in lipid metabolism and body weight control, SCD1 has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood. In order to provide insights into those mechanisms, genome-wide transcriptomic analyses were carried out in mRPE cells exposed to SA for 24 h. Integrative functional enrichment analysis of genome-wide expression data provided biological insight about the protective mechanisms induced by SA. On the one hand, pivotal genes related to fatty acid biosynthesis, steroid biosynthesis, cell death, actin-cytoskeleton reorganization and extracellular matrix-receptor interaction were significantly downregulated by exposition to SA. On the other hand, genes related to fatty acid degradation and beta-oxidation were significantly upregulated. In conclusion, SA administration to RPE cells regulates crucial pathways related to cell proliferation, inflammation and cell death that may be of interest for the treatment of ocular diseases.


Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 183
Author(s):  
Kevin M Mendez ◽  
Janice Kim ◽  
Inês Laíns ◽  
Archana Nigalye ◽  
Raviv Katz ◽  
...  

The purpose of this study was to analyze the association between plasma metabolite levels and dark adaptation (DA) in age-related macular degeneration (AMD). This was a cross-sectional study including patients with AMD (early, intermediate, and late) and control subjects older than 50 years without any vitreoretinal disease. Fasting blood samples were collected and used for metabolomic profiling with ultra-performance liquid chromatography–mass spectrometry (LC-MS). Patients were also tested with the AdaptDx (MacuLogix, Middletown, PA, USA) DA extended protocol (20 min). Two measures of dark adaptation were calculated and used: rod-intercept time (RIT) and area under the dark adaptation curve (AUDAC). Associations between dark adaption and metabolite levels were tested using multilevel mixed-effects linear modelling, adjusting for age, gender, body mass index (BMI), smoking, race, AMD stage, and Age-Related Eye Disease Study (AREDS) formulation supplementation. We included a total of 71 subjects: 53 with AMD (13 early AMD, 31 intermediate AMD, and 9 late AMD) and 18 controls. Our results revealed that fatty acid-related lipids and amino acids related to glutamate and leucine, isoleucine and valine metabolism were associated with RIT (p < 0.01). Similar results were found when AUDAC was used as the outcome. Fatty acid-related lipids and amino acids are associated with DA, thus suggesting that oxidative stress and mitochondrial dysfunction likely play a role in AMD and visual impairment in this condition.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 111-111
Author(s):  
Kingsley Kalu ◽  
Angelica Ly ◽  
Charles McMonnies ◽  
Jayashree Arcot

Abstract Objectives The aim of this study was to assess the dietary intakes of lutein, zeaxanthin (L + Z) and omega-3-essential fatty acid(EFA) among a selected population of Australian based adults and to examine the effect of specified risk factors for age-related macular degeneration(AMD) on those levels. Methods A cross-sectional study involving 70 adults aged 19–52 years was carried out. Demographic data were obtained using an online self-administered questionnaire while dietary intakes were estimated using USDA's 24 hours recall questionnaire, the Victorian Cancer Council(Australia) food frequency questionnaire and anthropometric characteristics were obtained using a body composition analyzer. Dietary intakes of lutein, zeaxanthin, omega-3-EFA and anthropometric indices against the risk of AMD were established using descriptive statistics and Spearman correlation. Results The mean age of the population was 29.9 ± 8.1years with 51% men and 49% women. Women had a higher intake of L + Z (1908.6 μg/day versus 1032.8 μg/day) and alpha-linolenic acid(ALA) compared to men(1.7 ± 1.1 g/day versus 1.6 ± 1.2 g/day). Men consumed more omega-3-EFA than women (433 ± 397.1 mg/day versus 365 ± 210.7 mg/day). L + Z levels were higher among people of Middle Eastern and South Asian origin (&gt;4000 μg/day) in the 19–25years age group. People of Middle Eastern, South East Asian and South Asian had the highest intake of omega-3-EFA(&gt;500 mg/day) at ages 19–25, 26–32 and 34–52years respectively. Women aged 34–52years with a family history of AMD had higher levels of L + Z(&gt;2500 μg/day) while women aged 26–32years with a family history of AMD had higher levels of ALA(&gt;3 g/day). Ethnicity and L + Z were correlated (P = −0.456, P &lt; 0.02). Higher levels of intake of L + Z (&gt;4000 μg/day) were seen in participants aged 34–52years with a 5–10years residence in Australia. Participants who had less than 5–10years of residency had higher levels of omega-3-EFA(&gt;500 mg/day) for ages 26–32years while those aged 34–52years who had less than 5years of residency had higher ALA(&gt;4 g/day). Conclusions Intake levels for L + Z vary significantly among participants. Culturally specific dietary habits could feasibly influence the levels of intake of L + Z. Intake levels of omega-3-EFA were met. This study provides detailed intake levels of L + Z and omega-3-EFA for the ‘at-risk’ AMD group. Funding Sources No funding source.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2283 ◽  
Author(s):  
Elena Piccinin ◽  
Marica Cariello ◽  
Stefania De Santis ◽  
Simon Ducheix ◽  
Carlo Sabbà ◽  
...  

The consumption of an olive oil rich diet has been associated with the diminished incidence of cardiovascular disease and cancer. Several studies have attributed these beneficial effects to oleic acid (C18 n-9), the predominant fatty acid principal component of olive oil. Oleic acid is not an essential fatty acid since it can be endogenously synthesized in humans. Stearoyl-CoA desaturase 1 (SCD1) is the enzyme responsible for oleic acid production and, more generally, for the synthesis of monounsaturated fatty acids (MUFA). The saturated to monounsaturated fatty acid ratio affects the regulation of cell growth and differentiation, and alteration in this ratio has been implicated in a variety of diseases, such as liver dysfunction and intestinal inflammation. In this review, we discuss our current understanding of the impact of gene-nutrient interactions in liver and gut diseases, by taking advantage of the role of SCD1 and its product oleic acid in the modulation of different hepatic and intestinal metabolic pathways.


2011 ◽  
Vol 57 (6) ◽  
pp. 604-614 ◽  
Author(s):  
T.A. Misharina ◽  
E.B. Burlakova ◽  
L.D. Fatkullina ◽  
M.B. Terenina ◽  
N.I. Krikunova ◽  
...  

Age-related alterations of fatty acid composition in liver and brain of AKR mice was investigated. The effect of savory essential oil (Satureja hortensis L.), added with drinking water on fatty acid composition in these organs and the processes of lipid peroxidation in erythrocytes were estimated. It was found that during aging the percentage of saturated fatty acids and polyunsaturated fatty acids decreased while monounsaturated fatty acids increased. The development of leukemia was accompanied by the increase of saturated and polyunsaturated fatty acids percentage and a decrease of monounsaturated fatty acids amount. In the liver aging caused the increase in the percentage of saturated fatty acids, the decrease of monounsaturated fatty acids, while the amount of polyunsaturated fatty acids was not changed. Leukemia (after 8 month) was accompanied by the increase of percentage of monounsaturated fatty acids and the decrease in the amount of oleinic and docosohexaenic acids. The intake of savory essential oil was accompanied by intensification of polyunsaturated fatty acids synthesis in mice liver and reduction of lipid peroxidation products content.


2013 ◽  
Vol 131 (3) ◽  
pp. 365 ◽  
Author(s):  
Adam T. Gerstenblith ◽  
Darrell E. Baskin ◽  
Chirag P. Shah ◽  
Jeremy D. Wolfe ◽  
Mitchell S. Fineman ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document