-
Nucleic Acids Research Feb 2019Small interfering RNA (siRNA)-based therapies are proving to be efficient for treating liver-associated disorders. However, extra-hepatic delivery remains challenging,...
Small interfering RNA (siRNA)-based therapies are proving to be efficient for treating liver-associated disorders. However, extra-hepatic delivery remains challenging, limiting therapeutic siRNA utility. We synthesized a panel of fifteen lipid-conjugated siRNAs and systematically evaluated the impact of conjugate on siRNA tissue distribution and efficacy. Generally, conjugate hydrophobicity defines the degree of clearance and the liver-to-kidney distribution profile. In addition to primary clearance tissues, several conjugates achieve significant siRNA accumulation in muscle, lung, heart, adrenal glands and fat. Oligonucleotide distribution to extra-hepatic tissues with some conjugates was significantly higher than with cholesterol, a well studied conjugate, suggesting that altering conjugate structure can enhance extra-hepatic delivery. These conjugated siRNAs enable functional gene silencing in lung, muscle, fat, heart and adrenal gland. Required levels for productive silencing vary (5-200 μg/g) per tissue, suggesting that the chemical nature of conjugates impacts tissue-dependent cellular/intracellular trafficking mechanisms. The collection of conjugated siRNA described here enables functional gene modulation in vivo in several extra-hepatic tissues opening these tissues for gene expression modulation. A systemic evaluation of a panel of conjugated siRNA, as reported here, has not previously been investigated and shows that chemical engineering of lipid siRNAs is essential to advance the RNA therapeutic field.
Topics: Animals; Carbocyanines; Cholesterol; Fatty Acids; Female; Fluorescent Dyes; Kidney; Lipids; Liver; Mice; Phosphorylcholine; RNA Interference; RNA, Small Interfering; Tissue Distribution
PubMed: 30544191
DOI: 10.1093/nar/gky1239 -
Current Opinion in Lipidology Feb 2022In contrast to other saturated fatty acids, very long-chain saturated fatty acids (VLSFAs) have received limited attention The purpose of this review is to summarize the... (Review)
Review
PURPOSE OF REVIEW
In contrast to other saturated fatty acids, very long-chain saturated fatty acids (VLSFAs) have received limited attention The purpose of this review is to summarize the associations of VLSFAs, including arachidic acid, behenic acid, and lignoceric acid, with cardiovascular disease outcomes and type 2 diabetes; to discuss the findings implications; and to call for future studies of the VLSFAs.
RECENT FINDINGS
Increased levels of circulating VLSFAs have been found associated with lower risks of incident heart failure, atrial fibrillation, coronary heart disease, mortality, sudden cardiac arrest, type 2 diabetes, and with better aging. The VLSFA associations are paralleled by associations of plasma ceramide and sphingomyelin species carrying a VLSFA with lower risks of heart failure, atrial fibrillation, and mortality, suggesting VLSFAs affect the biological activity of ceramides and sphingomyelins thereby impacting health. For diabetes, there is no such parallel and the associations of VLSFAs with diabetes may be confounded or mediated by triglyceride and circulating palmitic acid, possible biomarkers of de novo lipogenesis.
SUMMARY
In many ways, the epidemiology has preceded our knowledge of VLSFAs biology. We hope this review will spur interest from the research community in further studying these potentially beneficial fatty acids.
Topics: Atrial Fibrillation; Cardiovascular Diseases; Ceramides; Diabetes Mellitus, Type 2; Fatty Acids; Heart Failure; Humans
PubMed: 34907969
DOI: 10.1097/MOL.0000000000000806 -
Food Research International (Ottawa,... May 2017Obesity affects all social classes, making it necessary to develop effective products that aid weight loss or help prevent weight gain. The objective of this work was to...
Obesity affects all social classes, making it necessary to develop effective products that aid weight loss or help prevent weight gain. The objective of this work was to study the anti-obesity effects of structured lipids (SL) obtained by enzymatic interesterification, based on olive oil, soy oil and fully hydrogenated crambe oil. Twenty-four C57Bl/6 mice were distributed into four experimental groups according to the diet consumed: Control Diet (CD), Structured Lipids Diet (SLD), High-fat Control Diet (HCD), High-fat Structured Lipids Diet (HSLD). The animals that were fed SLs presented a smaller weight gain, despite a larger intake of the diet. The lowest weight gain was reflected in reduced amounts of adipose tissue and lower liver weight. A significant increase in lipids excreted by the animals in the feces was observed, despite there being no sign of toxicity or presence of diarrhea. The animals that consumed the HSLD presented lower total and LDL-cholesterol, increased HDL-cholesterol and increased hepatic arachidonic acid and docosahexaenoic acid levels. In addition, they did not develop hepatic steatosis. The study therefore showed that SLs could play a major role in combating or preventing obesity and other resultant diseases, without producing side effects.
Topics: Animals; Anti-Obesity Agents; Arachidonic Acid; Blood Glucose; Cholesterol; Diet, High-Fat; Docosahexaenoic Acids; Energy Metabolism; Fatty Acids; Fatty Liver; Feces; Insulin; Liver; Mice; Mice, Inbred C57BL; Obesity; Olive Oil; Triglycerides; Weight Gain
PubMed: 28395825
DOI: 10.1016/j.foodres.2017.03.005 -
Frontiers in Microbiology 2021Bacterial metabolites exhibit a variety of biologically active compounds including antibacterial and antifungal activities. It is well known that is considered to be a...
Bacterial metabolites exhibit a variety of biologically active compounds including antibacterial and antifungal activities. It is well known that is considered to be a promising source of bioactive secondary metabolites. Most plant pathogens have an incredible ability to mutate and acquire resistance, causing major economic losses in the agricultural field. Therefore, it is necessary to use the natural antibacterial compounds in microbes to control plant pathogens. This study was conducted to investigate the bio-active compounds of L2. According to the activity guidance of T-37, EC-1 and RS-2, five monomeric compounds, including erucamide (), behenic acid (), palmitic acid (), phenylacetic acid (), and β-sitosterol (), were fractionated and purified from the crude ethyl acetate extract of . To our knowledge, all compounds were isolated from the bacterium for the first time. To understand the antimicrobial activity of these compounds, and their minimum inhibitory concentrations (MICs) (range: 0.98∼500 μg/mL) were determined by the broth microdilution method. For the three tested pathogens, palmitic acid exhibited almost no antibacterial activity (>500 μg/mL), while erucamide had moderate antibacterial activity (MIC = 500 μg/mL). Behenic acid showed MICs of 250 μg/mL against T-37 and RS-2 strains with an antibacterial activity. β-sitosterol showed significant antimicrobial activity against RS-2. β-sitosterol showed remarkable antimicrobial activity against RS-2 with an MIC of 15.6 μg/mL. In addition, with the antimicrobial activity, against T-37 (62.5 μg/mL) and against EC-1 (125 μg/mL) and RS-2 (15.6 μg/mL) strains notably, phenylacetic acid may be interesting for the prevention and control of phytopathogenic bacteria. Our findings suggest that isolated compounds such as behenic acid, β-sitosterol, and phenylacetic acid may be promising candidates for natural antimicrobial agents.
PubMed: 33841370
DOI: 10.3389/fmicb.2021.645484 -
EFSA Journal. European Food Safety... Sep 2023Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to review a scientific assessment related to a...
Re-evaluation of behenic acid from mustard seeds to be used in the manufacturing of certain emulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 - for permanent exemption from labelling.
Following a request from the European Commission, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to review a scientific assessment related to a notification from DuPont Nutrition Biosciences Aps on behenic acid from mustard seeds to be used in the manufacturing of certain emulsifiers pursuant to Article 21(2) of Regulation (EU) No 1169/2011 - for permanent exemption from labelling. The EC requested EFSA to consider comments raised by the German authorities in relation to: (a) the maximum amount of mustard protein that could be consumed from the emulsifiers manufactured from behenic acid (E470a, E471 and E477) on a single occasion and (b) the minimal observed eliciting dose (MOED) triggering allergic reactions in mustard-allergic individuals. The maximum amount of mustard protein content in behenic acid was re-assessed in view of new analytical data provided by the applicant. Intake estimates by the EFSA ANS Panel for E471 (adults) were used as a proxy for the combined intake (E470a, E471 and E477). Food challenge data and systematic reviews thereof deriving population minimal observed eliciting dose distributions for mustard protein were used to calculate the MOED and estimate the risk. The margin of exposure between the MOED (0.26 mg mustard protein) and the maximum amount of mustard protein that could be consumed from the emulsifiers on a single occasion (0.00895475 mg) is 29. It is predicted that between 0.1% and 1% of the mustard allergic population would react with mild objective symptoms to that dose. Overall, the assessment is conservative, particularly in relation to the exposure. Based on the information and data available, the NDA Panel concludes that it is extremely unlikely (≤ 1% probability) that oral consumption of emulsifiers to be manufactured using behenic acid from mustard seeds (i.e. E470a, E471 and E477) will trigger an allergic reaction in mustard-allergic individuals under the proposed conditions of use.
PubMed: 37753350
DOI: 10.2903/j.efsa.2023.8240 -
Frontiers in Nutrition 2022Evidence regarding associations of circulating saturated fatty acids (SFAs) with chronic diseases is mixed. The objective of this study was to determine the associations...
BACKGROUND AND AIMS
Evidence regarding associations of circulating saturated fatty acids (SFAs) with chronic diseases is mixed. The objective of this study was to determine the associations between total or individual SFA biomarkers and the risk of cardiometabolic diseases.
METHODS
Four electronic databases were searched from inception to March 2022. Three investigators independently assessed for inclusion and extracted data. Random-effects or fixed-effects models was used to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs) for the association of total or individual SFA biomarkers, including even-chain SFAs (e.g., 14:0, myristic acid; 16:0, palmitic acid; 18:0, stearic acid), odd-chain SFAs (e.g., 15:0, pentadecanoic acid; 17:0, margaric acid) and very-long-chain SFAs (VLCSFAs; e.g., 20:0, arachidic acid; 22:0, behenic acid; 24:0, lignoceric acid), with risk of incident type 2 diabetes (T2D), cardiovascular disease [CVD; coronary heart disease (CHD) inclusive of stroke], CHD and stroke.
RESULTS
A total of 49 prospective studies reported in 45 articles were included. Higher concentration of circulating total SFAs was associated with an increasing risk of cardiometabolic diseases, the risk increased significantly by 50% for CVD (95%CI:1.31-1.71), 63% for CHD (95%CI:1.38-1.94), 38% for stroke (95%CI:1.05-1.82), respectively. Similarly, levels of even-chain SFAs were positively associated with higher risk of chronic diseases, with RRs ranging from 1.15 to 1.43. In contrast, the risk of cardiometabolic diseases was reduced with increasing odd-chain SFA levels, with RRs ranging from 0.62 to 0.91. A higher level of VLCSFAs corresponded to 19% reduction in CVD. Further dose-response analysis indicated that each 50% increment in percentage of total SFAs in circulating was associated with an 8% higher risk of T2D (RR: 1.08, 95%CI: 1.02-1.14) and trends toward higher risk of CVD (RR: 1.15, 95%CI: 0.98-1.34). Inverse linear relationships were observed between 17:0 biomarker and T2D or CVD risk.
CONCLUSION
Our findings support the current recommendations of reducing intake of saturated fat as part of healthy dietary patterns. Further studies are needed to confirm our findings on these SFAs in relation to cardiometabolic outcomes and to elucidate underlying mechanisms.
SYSTEMATIC REVIEW REGISTRATION
[https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022329182], identifier [CRD42022329182].
PubMed: 36046138
DOI: 10.3389/fnut.2022.963471 -
JAMA Network Open Aug 2021Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain...
IMPORTANCE
Identifying novel factors that protect against age-related diseases and promote healthy aging is critical to public health. Higher levels of circulating very-long-chain saturated fatty acids (VLSFAs) are integrated biomarkers of diet and metabolism shown to have beneficial associations in cardiovascular disease and total mortality, but whether they are associated with overall healthy aging is unknown.
OBJECTIVE
To examine the association of circulating levels of 3 VLSFAs with unhealthy aging events, including incident chronic disease (cardiovascular disease, cancer, lung disease or severe kidney disease), physical dysfunction, and cognitive decline.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used 1992 to 2014 data from the Cardiovascular Health Study (CHS). The CHS is a multicenter, population-based study of cardiovascular disease among older adults. Among the 4559 CHS participants with available fatty acid data, 1879 participants who had an age-related event before their first measurement were excluded. Data analysis was performed in 2020.
MAIN OUTCOMES AND MEASURES
Plasma phospholipid VLSFA levels were measured by thin-layer chromatography followed by gas chromatography. The main outcome was the hazard ratio (HR) of an incident unhealthy aging event associated with serial measures of plasma arachidic acid, behenic acid, and lignoceric acid.
RESULTS
Among the 2680 study participants (976 men [36.4%]), the mean (SD) age was 74.7 (4.8) years old at entry. During a median (interquartile range) of 6.4 (2.9-12.9) years of follow-up, 2484 participants experienced an unhealthy event. Compared with the lowest quintile, levels of behenic acid in the highest quintile of the fatty acid distribution were associated with 15% lower risk of an unhealthy event (HR, 0.85; 95% CI, 0.74-0.97; P for trend = .01) after adjustment for demographic characteristics, lifestyle factors, and clinical conditions. In analogous comparisons, levels of lignoceric acid were similarly associated with 16% lower risk of an unhealthy event (HR, 0.84; 95% CI, 0.73-0.95; P for trend = .001).
CONCLUSIONS AND RELEVANCE
These findings suggest that higher levels of circulating behenic acid and lignoceric acid are associated with lower risk of unhealthy aging events. These results highlight the need to explore determinants of circulating VLSFAs for potential novel efforts to promote healthy aging.
Topics: Aged; Aged, 80 and over; Biomarkers; California; Cardiovascular Diseases; Cohort Studies; Diagnostic Tests, Routine; Fatty Acids; Female; Healthy Aging; Humans; Life Style; Male; Maryland; North Carolina; Pennsylvania; Phospholipids
PubMed: 34383061
DOI: 10.1001/jamanetworkopen.2021.20616 -
Frontiers in Psychiatry 2023Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with...
Psychosis spectrum disorders (PSDs), as well as other severe mental illnesses where psychotic features may be present, like bipolar disorder, are associated with intrinsic metabolic abnormalities. Antipsychotics (APs), the cornerstone of treatment for PSDs, incur additional metabolic adversities including weight gain. Currently, major gaps exist in understanding psychosis illness biomarkers, as well as risk factors and mechanisms for AP-induced weight gain. Metabolomic profiles may identify biomarkers and provide insight into the mechanistic underpinnings of PSDs and antipsychotic-induced weight gain. In this 12-week prospective naturalistic study, we compared serum metabolomic profiles of 25 cases within approximately 1 week of starting an AP to 6 healthy controls at baseline to examine biomarkers of intrinsic metabolic dysfunction in PSDs. In 17 of the case participants with baseline and week 12 samples, we then examined changes in metabolomic profiles over 12 weeks of AP treatment to identify metabolites that may associate with AP-induced weight gain. In the cohort with pre-post data ( = 17), we also compared baseline metabolomes of participants who gained ≥5% baseline body weight to those who gained <5% to identify potential biomarkers of antipsychotic-induced weight gain. Minimally AP-exposed cases were distinguished from controls by six fatty acids when compared at baseline, namely reduced levels of palmitoleic acid, lauric acid, and heneicosylic acid, as well as elevated levels of behenic acid, arachidonic acid, and myristoleic acid (FDR < 0.05). Baseline levels of the fatty acid adrenic acid was increased in 11 individuals who experienced a clinically significant body weight gain (≥5%) following 12 weeks of AP exposure as compared to those who did not (FDR = 0.0408). Fatty acids may represent illness biomarkers of PSDs and early predictors of AP-induced weight gain. The findings may hold important clinical implications for early identification of individuals who could benefit from prevention strategies to reduce future cardiometabolic risk, and may lead to novel, targeted treatments to counteract metabolic dysfunction in PSDs.
PubMed: 37168086
DOI: 10.3389/fpsyt.2023.1169787 -
Food Science and Biotechnology Apr 2018A long chain saturated fatty acid (SFA), behenic acid, is incorporated into the -1, 3 positions of triacylglycerols in palm olein (POo) and high-oleic sunflower oil...
A long chain saturated fatty acid (SFA), behenic acid, is incorporated into the -1, 3 positions of triacylglycerols in palm olein (POo) and high-oleic sunflower oil (HOS) by solvent-free interesterification catalyzed by Lipozyme RM IM. The enzymatic interesterified HOS (EIE-HOS) yielded 76.5% of BOO and BOB as compared to 45.6% in POo (EIE-POo). The -2 position of EIE-HOS displayed 5.3 mol% of SFA which is significantly lower compared to 13.5 mol% in EIE-POo ( < 0.001). The -1, 3 positions of EIE-POo exhibited greater amount of behenic acid (82.0 mol%) in relation to EIE-HOS (64.0 mol%) ( < 0.001). Due to the greater variety of constitutive triacylglycerol, EIE-POo showed greater differences between onset (To) and offset temperature (Tf) in the melting endotherms (76.99 °C) as compared to EIE-HOS (68.65 °C), and may offer more intensive cooling sensation and flavor release.
PubMed: 30263758
DOI: 10.1007/s10068-017-0271-3 -
Lipids in Health and Disease Jul 2010Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial...
BACKGROUND
Dietary 1(3)-behenoyl-2,3(1)-dioleoyl-rac-glycerol (BOO) has been reported to inhibit pancreatic lipase activity in vitro and suppress postprandial hypertriacylglycerolemia in humans. In the present study, the anti-obesity activities of BOO and its inhibitory effects on lymphatic triacylglycerol (TAG) absorption were investigated in rats.
METHODS
In Experiment 1, rats were fed either BOO or soybean oil (SO) diet for 6 weeks. In the BOO diet, 20% of SO was replaced with an experimental oil rich in BOO. In Experiments 2 and 3, rats cannulated in the thoracic duct were administered an emulsions containing trioleoylglycerol (OOO) or an oil mixture (OOO:BOO, 9:1). Tri[1-14C]oleoylglycerol (14C-OOO) was added to the emulsions administered in Experiment 3.
RESULTS
No observable differences were detected in food intake or body weight gain between the BOO and SO groups in Experiment 1. Plasma and liver TAG concentrations and visceral fat weights were significantly lower in the BOO group than in the SO group. The apparent absorption rate of fat was significantly lower in the BOO group than in the SO group. In Experiment 2, the lymphatic recovery of oleic and behenic acids was significantly lower at 5 and 6 h after BOO administration than after OOO administration. In Experiment 3, the lymphatic recovery of 14C-OOO was significantly lower at 5 and 6 h after BOO administration than after OOO administration.
CONCLUSIONS
These results suggest that BOO prevents deposition of visceral fat and hepatic TAG by lowering and delaying intestinal absorption of TAG.
Topics: Animals; Anti-Obesity Agents; Cholesterol; Eating; Fat Substitutes; Fatty Acids; Feces; Hypertriglyceridemia; Intestinal Absorption; Intra-Abdominal Fat; Kinetics; Liver; Lymph; Lymphatic System; Male; Obesity; Oleic Acid; Organ Size; Rats; Rats, Wistar; Triglycerides; Weight Gain
PubMed: 20653972
DOI: 10.1186/1476-511X-9-77