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BMC Neurology Mar 2024RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the...
BACKGROUND
RARS2-related mitochondrial disorder is an autosomal recessive mitochondrial encephalopathy caused by biallelic pathogenic variants in the gene encoding the mitochondrial arginyl-transfer RNA synthetase 2 (RARS2, MIM *611524, NM_020320.5). RARS2 catalyzes the transfer of L-arginine to its cognate tRNA during the translation of mitochondrially-encoded proteins. The classical presentation of RARS2-related mitochondrial disorder includes pontocerebellar hypoplasia (PCH), progressive microcephaly, profound developmental delay, feeding difficulties, and hypotonia. Most patients also develop severe epilepsy by three months of age, which consists of focal or generalized seizures that frequently become pharmacoresistant and lead to developmental and epileptic encephalopathy (DEE).
CASE PRESENTATION
Here, we describe a six-year-old boy with developmental delay, hypotonia, and failure to thrive who developed an early-onset DEE consistent with Lennox-Gastaut Syndrome (LGS), which has not previously been observed in this disorder. He had dysmorphic features including bilateral macrotia, overriding second toes, a depressed nasal bridge, retrognathia, and downslanting palpebral fissures, and he did not demonstrate progressive microcephaly. Whole genome sequencing identified two variants in RARS2, c.36 + 1G > T, a previously unpublished variant that is predicted to affect splicing and is, therefore, likely pathogenic and c.419 T > G (p.Phe140Cys), a known pathogenic variant. He exhibited significant, progressive generalized brain atrophy and ex vacuo dilation of the supratentorial ventricular system on brain MRI and did not demonstrate PCH. Treatment with a ketogenic diet (KD) reduced seizure frequency and enabled him to make developmental progress. Plasma untargeted metabolomics analysis showed increased levels of lysophospholipid and sphingomyelin-related metabolites.
CONCLUSIONS
Our work expands the clinical spectrum of RARS2-related mitochondrial disorder, demonstrating that patients can present with dysmorphic features and an absence of progressive microcephaly, which can help guide the diagnosis of this condition. Our case highlights the importance of appropriate seizure phenotyping in this condition and indicates that patients can develop LGS, for which a KD may be a viable therapeutic option. Our work further suggests that analytes of phospholipid metabolism may serve as biomarkers of mitochondrial dysfunction.
Topics: Humans; Male; Child; Microcephaly; Muscle Hypotonia; Phenotype; Mitochondrial Diseases; Seizures; Arginine-tRNA Ligase
PubMed: 38438854
DOI: 10.1186/s12883-024-03571-w -
International Journal of Biological... Apr 2024The digestive instability of anthocyanins (ACNs) limits their application in food nutrition, especially precision nutrition. Blueberry ACNs-loaded nanoparticles...
Construction of nanoparticles from blueberry anthocyanins-lecithin/gum Arabic improves lipid droplet accumulation and gut microbiota disturbance in HFD-induced obese mice.
The digestive instability of anthocyanins (ACNs) limits their application in food nutrition, especially precision nutrition. Blueberry ACNs-loaded nanoparticles (Lipo/GA-ACNs NPs) were prepared using gum arabic (GA) as the delivery carrier and liposomal vesicles (Lipo) prepared from soy lecithin as the targeting scaffold. The average particle size of the NPs was 99.4 nm, and the polydispersion index (PDI) was 0.46. The results showed that the presence of the Lipo-GA matrix enhanced the NPs' in vitro stability and antioxidant activity. In addition, the in vitro biocompatibility, uptake ability, lipid-lowering activity, and free-radical scavenging ability were improved to a certain extent. In a high-fat diet (HFD)-induced obese mouse model, oral administration of ACNs-LNP (LNP, liver-targeted nanoparticle) showed better effects on body weight, liver injury, and lipid droplet accumulation in the liver than ACNs. In addition, ACNs-LNP also played a role in regulating HFD-induced gut microbiota imbalance. These results provide a promising ACNs delivery strategy with the potential to be developed into a functional food that targets the liver to prevent fatty liver.
Topics: Animals; Mice; Diet, High-Fat; Anthocyanins; Mice, Obese; Lecithins; Gum Arabic; Blueberry Plants; Gastrointestinal Microbiome; Lipid Droplets; Nanoparticles; Mice, Inbred C57BL
PubMed: 38437939
DOI: 10.1016/j.ijbiomac.2024.130595 -
Journal of Nutritional Science and... 2024In this study, we investigated the effects of a porcine liver protein hydrolysate (PLH) diet on lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a...
In this study, we investigated the effects of a porcine liver protein hydrolysate (PLH) diet on lipid metabolism in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type II diabetes. OLETF rats (20-wk-old males) were pair-fed with either a PLH diet containing 20% PLH or a casein diet for 14 wk. Dietary PLH significantly lowered serum cholesterol and phospholipid concentrations, mainly by decreasing low-density lipoprotein and high-density lipoprotein fractions. Fecal cholesterol was significantly increased in the PLH diet group; however, the total bile acid concentration in the feces was not significantly different between the groups. In addition, the PLH diet significantly decreased serum thiobarbituric acid reactive substance concentrations. These results suggest that dietary PLH exerts hyperlipidemic and antioxidant effects, indicating that it is a novel functional food ingredient.
Topics: Rats; Male; Animals; Swine; Rats, Inbred OLETF; Diabetes Mellitus, Type 2; Antioxidants; Protein Hydrolysates; Pork Meat; Red Meat; Liver; Cholesterol
PubMed: 38417848
DOI: 10.3177/jnsv.70.19 -
EBioMedicine Mar 2024Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.
Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC).
BACKGROUND
Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.
METHODS
In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.
FINDINGS
Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (OR 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (OR 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.
INTERPRETATION
Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations.
FUNDING
World Cancer Research Fund (reference: 2013/1002); European Commission (FP7: BBMRI-LPC; reference: 313010).
Topics: Humans; Female; Male; Prospective Studies; Risk Factors; Case-Control Studies; Colorectal Neoplasms; Sphingolipids; Phosphatidylcholines
PubMed: 38412638
DOI: 10.1016/j.ebiom.2024.105024 -
Frontiers in Veterinary Science 2024It has been demonstrated that supplementing late-gestation cow diets with NCG (N-carbamoylglutamic acid) increases the serum protein level, boosts immunological...
It has been demonstrated that supplementing late-gestation cow diets with NCG (N-carbamoylglutamic acid) increases the serum protein level, boosts immunological function, and increases the birth weight of the calves. However, the underlying mechanism remains unclear. In this experiment, 30 late-gestation Angus heifers almost at same conditions were chosen for this experiment. They were randomly divided into two groups of 15 cows each. A basal diet was provided to the control group, and 30 g/(d-head) of NCG was added to the basal diet of the test group (NCG group). Blood samples were collected from the jugular vein after birth and before the end (when the calves were 90 days old) of the experiment for plasma metabolomics analysis. The metabolomics analysis identified 53 metabolites between the NCG group and control group, with 40 significantly up-regulated and 13 significantly down-regulated. Among them, 33 lipids and lipid-like molecules made up 57.89% of all the metabolites that were found. Thirty-three metabolic pathways enriched by metabolites showed p.adjust <0.05, among which glycerophospholipid and sphingolipid metabolism pathways were the most abundant. In conclusion, the addition of NCG in late-gestation cows appears to primarily affect calf growth and development through the regulation of phospholipid metabolism, which plays a role in nerve conduction, brain activity, and cell metabolism and function. This study provides valuable insights into how nutritional supplementation by late-gestation cows might improve the growth and development of newborn calves.
PubMed: 38410738
DOI: 10.3389/fvets.2024.1335897 -
The American Journal of Clinical... Apr 2024Evidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance...
BACKGROUND
Evidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance thyroid function.
OBJECTIVES
We investigated whether early pregnancy plasma phospholipid PUFAs could benefit maternal thyroid function across pregnancy, which is critical to fetal brain development and growth in pregnancy.
METHODS
Within the National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort, we collected plasma samples longitudinally from 214 subjects [107 with gestational diabetes mellitus (GDM) matched with 107 controls] with a singleton pregnancy. We measured 11 PUFAs at early pregnancy (10-14 wk) and 5 thyroid biomarkers at 10-14, 15-26, 23-31, and 33-39 wk, including free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, antithyroid peroxidase, and antithyroglobulin. Associations of PUFAs with thyroid function biomarkers and relative risk (RR) of gestational hypothyroidism (GHT) during pregnancy were assessed using generalized linear mixed models and modified Poisson regression, respectively.
RESULTS
After sample weighting because of subjects with GDM over-representing in the analytic sample with biomarkers, eicosapentaenoic acid (EPA) at early pregnancy was associated with a reduction of 0.24 pmol/L (95% confidence intervals: -0.31, -0.16) in fT3 across gestation per standard deviation (SD) increment, whereas docosahexaenoic acid (DHA) at early pregnancy was associated with an increment of 0.04 ng/dL (0.02, 0.05) in fT4 across gestation per SD increment. Furthermore, EPA and docosatetraenoic acid (DTA) were associated with lower risks of persistent GHT (EPA-RR: 0.13; 0.06, 0.28; DTA-RR: 0.24; 0.13, 0.44) per SD increment. All significant associations remained robust in sensitivity analysis and multiple testing.
CONCLUSIONS
Certain plasma phospholipid PUFAs were associated with optimal levels of thyroid biomarkers and even lower risk of GHT throughout pregnancy, which might be potentially targeted for maternal thyroid regulation in early pregnancy.
CLINICAL TRIAL REGISTRY
This trial was registered at https://beta.
CLINICALTRIALS
gov/study/NCT00912132?distance=50&term=NCT00912132&rank=1 as NCT00912132.
Topics: Pregnancy; Female; Child; Humans; Longitudinal Studies; Phospholipids; Thyroid Gland; Fatty Acids, Unsaturated; Diabetes, Gestational; Eicosapentaenoic Acid; Biomarkers; Fatty Acids
PubMed: 38408725
DOI: 10.1016/j.ajcnut.2024.02.016 -
Animals : An Open Access Journal From... Feb 2024(TM) is considered as one of the most promising protein sources for replacing fish meal in aquafeeds, among other things because it is rich in protein, a good source of...
(TM) is considered as one of the most promising protein sources for replacing fish meal in aquafeeds, among other things because it is rich in protein, a good source of micronutrients and has a low carbon footprint and land use. However, the main drawback of TM is its fatty acid profile, in particular its low content of n-3 PUFA. This study evaluates the effects of partially replacing plant or marine-derived with full-fat TM meal at two different levels on growth performance and lipid profiles of Senegalese sole (). For this purpose, a control diet (CTRL) and four experimental isoproteic (53%) and isolipidic (16%) diets were formulated containing 5 and 10% TM meal replacing mostly fish meal (FM5 and FM10), or 10 and 15% TM meal replacing mostly plant meal (PP10 and PP15). Fish (215 g) were fed at 1% of their body weight for 98 days. The final body weight of fish fed the experimental diets containing TM meal was not different from that of fish fed the CTRL diet (289 g). However, the inclusion of TM meal resulted in a gradual improvement in growth rate and feed efficiency in both cases (replacement of fish or plant meals), and significant differences in specific growth rate (SGR) were observed between fish fed the CTRL diet (SGR = 0.30% day) and those fed diets with the highest TM meal content (PP15; SGR = 0.35% day). The experimental groups did not show any differences in the protein content of the muscle (19.6% /). However, significant differences were observed in the total lipid content of the muscle, with the FM10, PP10, and PP15 groups having the lowest muscle lipid contents (2.2% ww). These fish also showed the lowest neutral lipid content in muscle (6.6% dw), but no differences were observed in the total phospholipid content (2.6% dw). Regarding the fatty acid profile, fish fed FM10, PP10 and PP15 had lower levels of linoleic acid (18:2n-6) and higher levels of oleic acid (18:1n-9) in liver and muscle compared to fish fed CTRL. However, no differences were found between fish fed CTRL and TM-based diets for docosahexaenoic acid (22:6n-3) and total n-3 PUFA in liver and muscle. In conclusion, our study demonstrated that full-fat TM inclusion up to 15% in diets had no negative effects or even some positive effects on fish survival, growth performance, nutrient utilization and flesh quality.
PubMed: 38396563
DOI: 10.3390/ani14040595 -
Journal of Dairy Science Jul 2024The objective of the experiment was to determine the effects of supplemental SFA sources, lysophospholipids (LPL), and their interaction on production and nutrient...
The objective of the experiment was to determine the effects of supplemental SFA sources, lysophospholipids (LPL), and their interaction on production and nutrient digestibility in lactating dairy cows. The experiment was conducted with 48 cows in a randomized complete block design. Cows were blocked (12 blocks total) by parity and days in milk and randomly assigned to 4 dietary treatments in each block (2 × 2 factorial arrangement), i.e., 2 sources of fat supplements, C16:0 (PA)- or C18:0 (SA)-enriched fat, and with or without LPL. The experiment was conducted for 6 wk to measure daily dry matter intake, milk yield, and weekly milk composition. During the last week of the experiment, spot fecal and urine samples were collected to determine total-tract nutrient digestibility. Milk samples in the last week were also collected to analyze the milk fatty acid (FA) profile. All data were analyzed using the MIXED procedure of SAS, where block was used as a random effect and FA, LPL, and the interaction of FA by LPL were used as fixed effects. Week and interactions of week by FA or LPL were included for production measures. Different sources of SFA did not affect dry matter intake and milk yield. However, the PA treatment increased (39.7 vs. 36.8 kg) energy-corrected milk compared with SA due to increased milk fat yield. No effect of LPL on production measures was observed. Total-tract digestibilities of dry matter, organic matter, crude protein, and total FA were not different between the PA and SA groups, but PA increased (41.4% vs. 38.8%) neutral detergent fiber digestibility compared with SA. Supplementation of LPL increased (64.7% vs. 60.5%) total FA digestibility, especially 18-carbon FA (74.1% vs. 68.2%). An interaction of SFA by LPL was found for 16-carbon FA digestibility. The PA diet increased the concentration of 16-carbon FA in milk fat and SA increased the concentration of preformed FA (≥18 carbons). Supplementation of LPL decreased the concentration of trans-10 C18:1. No difference in N utilization and excretion among treatments was observed. In conclusion, the PA diet was more effective in improving milk fat yield of lactating cows compared with SA. Supplementation of LPL increased digestibility of total FA, especially 18-carbon FA but did not affect production.
Topics: Animals; Cattle; Lactation; Female; Milk; Diet; Lysophospholipids; Fatty Acids; Digestion; Animal Feed; Dietary Supplements; Nutrients
PubMed: 38395396
DOI: 10.3168/jds.2023-24457 -
Marine Drugs Feb 2024The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However,... (Review)
Review
The products of oleaginous microbes, primarily lipids, have gained tremendous attention for their health benefits in food-based applications as supplements. However, this emerging biotechnology also offers a neuroprotective treatment/management potential for various diseases that are seldom discussed. Essential fatty acids, such as DHA, are known to make up the majority of brain phospholipid membranes and are integral to cognitive function, which forms an important defense against Alzheimer's disease. Omega-3 polyunsaturated fatty acids have also been shown to reduce recurrent epilepsy seizures and have been used in brain cancer therapies. The ratio of omega-3 to omega-6 PUFAs is essential in maintaining physiological function. Furthermore, lipids have also been employed as an effective vehicle to deliver drugs for the treatment of diseases. Lipid nanoparticle technology, used in pharmaceuticals and cosmeceuticals, has recently emerged as a biocompatible, biodegradable, low-toxicity, and high-stability means for drug delivery to address the drawbacks associated with traditional medicine delivery methods. This review aims to highlight the dual benefit that lipids offer in maintaining good health for disease prevention and in the treatment of neurological diseases.
Topics: Humans; Fatty Acids, Omega-3; Dietary Supplements; Brain; Phospholipids; Epilepsy
PubMed: 38393051
DOI: 10.3390/md22020080 -
Renal Failure Dec 2024To investigate the preventive effect of aerobic exercise on renal damage caused by obesity.
PURPOSE
To investigate the preventive effect of aerobic exercise on renal damage caused by obesity.
METHODS
The mice in the Control (Con) and Control + Exercise (Con + Ex) groups received a standard chow diet for the 21-week duration of the study, while the High-fat diet (HFD) group and High-fat diet + Exercise (HFD + Ex) group were fed an HFD. Mice were acclimated to the laboratory for 1 week, given 12 weeks of being on their respective diets, and then the Con + Ex and HFD + Ex groups were subjected to moderate intensity aerobic treadmill running 45 min/day, 5 days/week for 8 weeks.
RESULTS
We found that HFD-induced obesity mainly impacts kidney glycerin phospholipids, glycerides, and fatty acyls, and aerobic exercise mainly impacts kidney glycerides, amino acids and organic acids as well as their derivatives. We identified 18 metabolites with significantly altered levels that appear to be involved in aerobic exercise mediated prevention of HFD-induced obesity and renal damage, half of which were amino acids and organic acids and their derivatives.
CONCLUSION
Aerobic exercise rewires kidney metabolites to reduce high-fat diet-induced obesity and renal injury.
Topics: Mice; Animals; Diet, High-Fat; Physical Conditioning, Animal; Obesity; Kidney; Glycerides; Amino Acids; Mice, Inbred C57BL
PubMed: 38390733
DOI: 10.1080/0886022X.2023.2286330