-
Nature Communications Jul 2024Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly...
Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.
Topics: Animals; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Mice; Mitochondria; Humans; X Chromosome; Docosahexaenoic Acids; Induced Pluripotent Stem Cells; Gene Dosage; Mice, Inbred C57BL; Blood Glucose; Glucose; Diabetes Mellitus
PubMed: 38956041
DOI: 10.1038/s41467-024-49764-2 -
Lipids in Health and Disease Jun 2024An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial....
BACKGROUND
An imbalance in lipid metabolism has been linked to the development of AMD, but the causal relationship between AMD and plasma fatty acids (FAs) remains controversial. Using a two-sample Mendelian randomization (MR) approach, we sought to evaluate the impact of specific FA plasma levels on the risk of different AMD subtypes.
METHODS
We analysed genome-wide association data of circulating FAs from 115,006 European-descended individuals in the UK Biobank. These data were used in a two-sample MR framework to assess the potential role of circulating FAs in developing wet and dry AMD. Sensitivity analyses were conducted to ensure the robustness of our findings. Additional multivariable and locus-specific MR analyses were conducted to evaluate direct effects of FA on AMD subtypes, minimizing biases from lipoprotein-related traits and triglycerides.
RESULTS
Mendelian randomization revealed associations of omega-3 was associated with decreased wet (OR 0.78, 95%CI 0.66-0.92) and dry AMD (0.85, 0.74-0.97) risk, showed a protective effect on AMD. Notably, the omega-6 to omega-3 ratio showed potential causal effects on both wet (1.27, 1.03-1.56) and dry AMD (1.18, 1.02-1.37). Multivariable MR suggested that the causal relationship of omega-3, omega-6 to omega-3 ratio on wet AMD persists after conditioning on HDL, LDL and triglycerides, albeit with slightly diminished evidence strength. Locus-specific MR linked to omega-3(FADS1, 0.89, 0.82-0.98; FADS2, 0.88, 0.81-0.96) and omega-6 to omega-3 ratio (FADS1, 1.10, 1.02-1.20; FADS2, 1.11, 1.03-1.20) suggests causal effects of these factors on wet AMD.
CONCLUSIONS
The associations between plasma FA concentrations and AMD, suggest potential causal role of omega-3, and the omega-6 to omega-3 ratio in wet AMD. These results underscore the impact of an imbalanced circulating omega-3 and omega-6 FA ratio on AMD pathophysiology from MR perspective.
Topics: Humans; Mendelian Randomization Analysis; Macular Degeneration; Fatty Acids, Omega-3; Genome-Wide Association Study; Male; Delta-5 Fatty Acid Desaturase; Female; Fatty Acids, Omega-6; Aged; Polymorphism, Single Nucleotide; Fatty Acid Desaturases; Middle Aged; Triglycerides; Fatty Acids; Risk Factors
PubMed: 38951820
DOI: 10.1186/s12944-024-02197-8 -
Tropical Animal Health and Production Jun 2024This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp)...
The benefits of flushing with Lemuru fish oil as a source of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on the performance of reproductive parameters in Garut ewes.
This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.94 kg were assigned into four experimental treatment groups. The experimental diets contained roughage: concentrate (30:70%) designated as control concentrate (CNT), flushing concentrate with 6% palm oil (PO), flushing concentrate with 3% palm oil mixed with 3% lemuru oil as DHA and EPA sources (PFO), and flushing concentrate with the addition of 6% lemuru oil (FO). Treatment animals were fed two weeks before and after conception and parturition (8 weeks of total flushing treatment). The addition of fish oil at either 3% (PFO) or 6% (FO) resulted in significantly higher reproductive performance of ewes by increasing the litter size, as reflected by the birth of multiple kids (P < 0.05) compared to CNT and PO. Adding fish oil (PFO and FO) also maintains gestation, resulting in increased lamb yield, especially in the FO treatment, which yields the highest lamb yield (0% single lamb birth). The lamb male ratio was also higher with fish oil supplementation (PFO and PO) (P < 0.05). This research revealed a positive effect of 6% Lemuru oil on decreasing embryo loss and increasing the proportion of twin births. These findings thus support the hypothesis that ration flushing with double the required DHA and EPA from 6% Lemuru fish oil (FO) resulted in significantly higher reproductive performance in Garut sheep.
Topics: Animals; Female; Eicosapentaenoic Acid; Docosahexaenoic Acids; Fish Oils; Animal Feed; Dietary Supplements; Reproduction; Diet; Sheep, Domestic; Pregnancy
PubMed: 38949740
DOI: 10.1007/s11250-024-04060-5 -
Nihon Yakurigaku Zasshi. Folia... 2024Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed...
Typical monoamine-based antidepressants have significant limitations, including a time lag for therapeutic response and low efficacy (more than one-third of depressed patients fail to respond to multiple antidepressant medications and are considered treatment-resistant). Conversely, ketamine, an N-methyl-D-aspartate receptor antagonist, exhibits rapid and sustained antidepressant actions in patients with treatment-resistant depression. However, clinical use of ketamine is limited due to its serious side effects. Thus, there is a significant need to develop novel ketamine-like antidepressants with fewer side effects. We previously demonstrated that intracerebroventricular infusion of resolvins (RvD1, RvD2, RvE1, RvE2, and RvE3), specialized pro-resolving lipid mediators derived from docosahexaenoic and eicosapentaenoic acids, produce antidepressant-like effects in mouse models of depression. Among resolvins, RvE1 produces the most potent antidepressant-like effects likely via ChemR23 in several mouse models of depression. Local infusion of RvE1 into the medial prefrontal cortex (mPFC) or dorsal hippocampal dentate gyrus (DG) also produces antidepressant-like effects, suggesting that these brain regions are sites of action of RvE1. Additionally, intranasal (i.n.) administration of RvE1 produces antidepressant-like effects through mechanisms similar to ketamine: activity-dependent release of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), and subsequent mechanistic target of rapamycin complex 1 (mTORC1) activation in the mPFC play a crucial role in the rapid and sustained antidepressant-like actions of i.n. RvE1. Moreover, the antidepressant-like effects of i.n. RvE1 require BDNF and VEGF release, but not mTORC1 activation, in the dorsal DG. These findings suggest that RvE1 can be a promising lead for a novel rapid-acting antidepressant.
Topics: Animals; Humans; Mice; Antidepressive Agents; Depression; Eicosapentaenoic Acid
PubMed: 38945902
DOI: 10.1254/fpj.23008 -
Food Research International (Ottawa,... Aug 2024Radio frequency (RF) heating has been proved an alternative roasting method for peanuts, which could effectively degrade aflatoxins and possesses the advantages of...
Radio frequency (RF) heating has been proved an alternative roasting method for peanuts, which could effectively degrade aflatoxins and possesses the advantages of greater heating efficiency and penetration depth. This study aimed to investigate the influences of RF roasting on the lipid profile of peanut oil under 150 °C target temperature with varied peanut moisture contents (8.29 % and 20 %) and holding times (0, 7.5, and 15 min), using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based lipidomics. In total, 2587 lipid species from 35 subclasses were identified. After roasting, the contents of sterol lipid (ST) and subclasses of glycerophospholipids (GPs) and glycoglycerolipids increased significantly, while fatty acid (FA), Oxidized (Ox-) FA, cholesterol (CE), and all subclasses of glycerolipids (GLs) decreased, and 1084 differential lipids were screened. The highest ST and lowest CE contents in peanut oil were achieved by medium roasting (7.5 min). The raise in moisture content of peanut simply affected a few GPs subclasses adversely. Compared with hot air (HA) roasting, RF decelerated lipid oxidation, showing higher levels of diacylglycerol, triacylglycerol and FA, with no additional negative impact and only 69 exclusive differential lipids. During RF roasting, hydrolysis and oxidation of fatty acyl chains into secondary oxides were the central behaviors of lipids transformation. This study could provide insights into the lipid changes and transformation mechanism of peanut oil by RF roasting processing.
Topics: Peanut Oil; Lipidomics; Cooking; Hot Temperature; Lipids; Tandem Mass Spectrometry; Radio Waves; Arachis; Fatty Acids; Chromatography, High Pressure Liquid; Food Handling; Oxidation-Reduction
PubMed: 38945611
DOI: 10.1016/j.foodres.2024.114592 -
International Journal of Biological... Jun 2024Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and...
Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC < 1 μM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (K < 1 μM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo.
PubMed: 38945336
DOI: 10.1016/j.ijbiomac.2024.133523 -
Revista de La Facultad de Ciencias... Jun 2024Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD).
INTRODUCTION
Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD).
AIM
The aim of this study was to determine food intakes patters and estimate risk of GD.
METHODS
A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks.
RESULTS
The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish).
CONCLUSION
Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor.
Topics: Humans; Argentina; Female; Male; Case-Control Studies; Cross-Sectional Studies; Middle Aged; Adult; Risk Factors; Feeding Behavior; Retrospective Studies; Cholelithiasis; Aged; Diet; Prevalence
PubMed: 38941231
DOI: 10.31053/1853.0605.v81.n2.36961 -
Food Additives & Contaminants. Part A,... Jun 2024Bakery products, including biscuits, cakes and breads, generally present a high content of simple sugars of rapid absorption, high fat content and low amount of dietary...
Bakery products, including biscuits, cakes and breads, generally present a high content of simple sugars of rapid absorption, high fat content and low amount of dietary fiber, which make them highly caloric foods. Although sucrose is a very important ingredient in bakery products for its preservation characteristics and a significant source of energy, there is a growing interest in replacing this sugar with alternative substances, such as high-intensity sweeteners (HIS) that provide sweetness with no or low calories. In Brazil, there is no data on the use of HIS in this class of food. Therefore, the objective of this study was to evaluate the presence of HIS in baked food commercially available in the country and estimate the dietary exposure to these food additives. For that, an analytical method was established for the simultaneous determination of nine HIS in bakery products using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Sample preparation steps were required based on mechanical kneading for homogenization, hexane extraction of fats, dilution in mobile phase and vortex homogenization, prior to injection into the system. The results obtained during validation showed that coefficients of variation (CV%) for precision were lower than 13.8% and the accuracy was between 91.6% and 109.1%. Aspartame, acesulfame potassium, sodium cyclamate, saccharin, sucralose and steviol glycosides were found in the samples, used alone or in combinations of up five substances. Steviol glycosides were the most found HIS in biscuit samples, while sucralose was the most common sweetener in cake and bread samples. Analysis of product labels revealed only three different claims, .i.e. 'no sugar', 'no added sugar' and 'zero sugar', with the latter being found in 70% of the samples. Exposure to HIS through the consumption of bakery products estimated per eating occasion showed no concerns regarding toxicological risk.
PubMed: 38940750
DOI: 10.1080/19440049.2024.2371929 -
Pharmaceutics May 2024Secondary metabolites, polyphenols, are widespread in the entire kingdom of plants. They contain one or more hydroxyl groups that have a variety of biological functions... (Review)
Review
Secondary metabolites, polyphenols, are widespread in the entire kingdom of plants. They contain one or more hydroxyl groups that have a variety of biological functions in the natural environment. These uses include polyphenols in food, beauty products, dietary supplements, and medicinal products and have grown rapidly during the past 20 years. Antimicrobial polyphenols are described together with their sources, classes, and subclasses. Polyphenols are found in different sources, such as dark chocolate, olive oil, red wine, almonds, cashews, walnuts, berries, green tea, apples, artichokes, mushrooms, etc. Examples of benefits are antiallergic, antioxidant, anticancer agents, anti-inflammatory, antihypertensive, and antimicrobe properties. From these sources, different classes of polyphenols are helpful for the growth of internal functional systems of the human body, providing healthy fats, vitamins, and minerals, lowering the risk of cardiovascular diseases, improving brain health, and rebooting our cellular microbiome health by mitochondrial uncoupling. Among the various health benefits of polyphenols (curcumin, naringenin, quercetin, catechin, etc.) primarily different antimicrobial activities are discussed along with possible future applications. For polyphenols and antimicrobial agents to be proven safe, adverse health impacts must be substantiated by reliable scientific research as well as in vitro and in vivo clinical data. Future research may be influenced by this evaluation.
PubMed: 38931842
DOI: 10.3390/pharmaceutics16060718 -
Sensors (Basel, Switzerland) Jun 2024The monitoring of body temperature is a recent addition to the plethora of parameters provided by wellness and fitness wearable devices. Current wearable temperature...
The monitoring of body temperature is a recent addition to the plethora of parameters provided by wellness and fitness wearable devices. Current wearable temperature measurements are made at the skin surface, a measurement that is impacted by the ambient environment of the individual. The use of near-infrared spectroscopy provides the potential for a measurement below the epidermal layer of skin, thereby having the potential advantage of being more reflective of physiological conditions. The feasibility of noninvasive temperature measurements is demonstrated by using an in vitro model designed to mimic the near-infrared spectra of skin. A miniaturizable solid-state laser-diode-based near-infrared spectrometer was used to collect diffuse reflectance spectra for a set of seven tissue phantoms composed of different amounts of water, gelatin, and Intralipid. Temperatures were varied between 20-24 °C while collecting these spectra. Two types of partial least squares (PLS) calibration models were developed to evaluate the analytical utility of this approach. In both cases, the collected spectra were used without pre-processing and the number of latent variables was the only optimized parameter. The first approach involved splitting the whole dataset into separate calibration and prediction subsets for which a single optimized PLS model was developed. For this first case, the coefficient of determination (R) is 0.95 and the standard error of prediction (SEP) is 0.22 °C for temperature predictions. The second strategy used a leave-one-phantom-out methodology that resulted in seven PLS models, each predicting the temperatures for all spectra in the held-out phantom. For this set of phantom-specific predicted temperatures, R and SEP values range from 0.67-0.99 and 0.19-0.65 °C, respectively. The stability and reproducibility of the sample-to-spectrometer interface are identified as major sources of spectral variance within and between phantoms. Overall, results from this in vitro study justify the development of future in vivo measurement technologies for applications as wearables for continuous, real-time monitoring of body temperature for both healthy and ill individuals.
Topics: Phantoms, Imaging; Spectroscopy, Near-Infrared; Humans; Least-Squares Analysis; Calibration; Skin; Gelatin; Temperature; Water; Wearable Electronic Devices; Emulsions; Soybean Oil; Phospholipids
PubMed: 38931768
DOI: 10.3390/s24123985