-
Science Advances May 2024Lipid droplets (LDs) comprise a triglyceride core surrounded by a lipid monolayer enriched with proteins, many of which function in LD homeostasis. How proteins are...
Lipid droplets (LDs) comprise a triglyceride core surrounded by a lipid monolayer enriched with proteins, many of which function in LD homeostasis. How proteins are targeted to the growing LD is still unclear. Rab1b, a GTPase regulating secretory transport, was recently associated with targeting proteins to LDs in a Drosophila RNAi screen. LD formation was prevented in human hepatoma cells overexpressing dominant-negative Rab1b. We thus hypothesized that Rab1b recruits lipid-synthesizing enzymes, facilitating LD growth. Here, FRET between diacylglycerol acyltransferase 2 (DGAT2) and Rab1b and activity mutants of the latter demonstrated that Rab1b promotes DGAT2 ER to the LD surface redistribution. Last, alterations in LD metabolism and DGAT2 redistribution, consistent with Rab1b activity, were caused by mutations in the Rab1b-GTPase activating protein TBC1D20 in Warburg Micro syndrome (WARBM) model mice fibroblasts. These data contribute to our understanding of the mechanism of Rab1b in LD homeostasis and WARBM, a devastating autosomal-recessive disorder caused by mutations in TBC1D20.
Topics: Lipid Droplets; Animals; Humans; rab1 GTP-Binding Proteins; Diacylglycerol O-Acyltransferase; Mice; Endoplasmic Reticulum; Mutation; Lipid Metabolism; GTPase-Activating Proteins
PubMed: 38809969
DOI: 10.1126/sciadv.ade7753 -
Scientific Reports Apr 2024Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain...
Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10 and 4.3 × 10). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD.
Topics: Humans; Alzheimer Disease; Neurodegenerative Diseases; Multiomics; Neuroimaging; Biomarkers; Lipids; Cognitive Dysfunction; Disease Progression
PubMed: 38565541
DOI: 10.1038/s41598-024-56837-1 -
Frontiers in Endocrinology 2023Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease. As a clinical empirical prescription of traditional Chinese medicine, Qushi Huayu decoction (QHD)...
INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease. As a clinical empirical prescription of traditional Chinese medicine, Qushi Huayu decoction (QHD) has attracted considerable attention for its advantages in multi-target treatment of NAFLD. However, the intervention mechanism of QHD on abnormal lipid levels and gut microbiota in NAFLD has not been reported.
METHODS
Therefore, we verified the therapeutic effect of QHD on high-fat diet (HFD)-induced NAFLD in rats by physiological parameters and histopathological examination. In addition, studies on gut microbiota and serum lipidomics based on 16S rRNA sequencing and ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) were conducted to elucidate the therapeutic mechanism of NAFLD in QHD.
RESULTS
The changes in gut microbiota in NAFLD rats are mainly reflected in their diversity and composition, while QHD treated rats restored these changes. The genera and were predominant in the NAFLD group, whereas, , and were predominant in the NAFLD+QHD group. Lipid subclasses, including diacylglycerol (DG), triglycerides (TG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidic acid (PA), phosphatidylserine (PS), lysophosphatidylinositol (LPI), and phosphatidylglycerol (PG), were significantly different between the NAFLD and the control groups, while QHD treatment significantly altered the levels of DG, TG, PA, lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and platelet activating factor (PAF). Finally, Spearman's correlation analysis showed that NAFLD related differential lipid molecules were mainly associated with the genera of , and , which were also significantly correlated with the biological parameters of NAFLD.
DISCUSSION
Taken together, QHD may exert beneficial effects by regulating the gut microbiota and thus intervening in serum lipids.
Topics: Rats; Animals; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Chromatography, Liquid; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Triglycerides
PubMed: 37900123
DOI: 10.3389/fendo.2023.1272214 -
Frontiers in Immunology 2023Novel preventive strategies in periodontal disease target the bacterial-induced inflammatory host response to reduce associated tissue destruction. Strategies focus on...
INTRODUCTION
Novel preventive strategies in periodontal disease target the bacterial-induced inflammatory host response to reduce associated tissue destruction. Strategies focus on the modulation of tissue-destroying inflammatory host response, particularly the reduction of inflammation and promotion of resolution. Thereby, nutrition is a potent immunometabolic non-pharmacological intervention. Human studies have demonstrated the benefit of olive oil-containing Mediterranean-style diets (MDs), the main component of which being mono-unsaturated fatty acid (FA) oleic acid (OA (C18:1)). Hence, nutritional OA strengthened the microarchitecture of alveolar trabecular bone and increased circulating pro-resolving lipid mediators following bacterial inoculation with periodontal pathogen , contrary to saturated FA palmitic acid (PA (C16:0)), which is abundant in Western-style diets. Additionally, the generalized distribution of inflammatory pathway mediators can occur in response to bacterial infection and compromise systemic tissue metabolism and bone homeostasis distant from the side of infection. Whether specific FA-enriched nutrition and periodontal inoculation are factors in systemic pathology that can be immune-modulatory targeted through dietary substitution is unknown and of clinical relevance.
METHODS
Normal-weight C57BL/6-mice received OA-or PA-enriched diets (PA-ED, OA-ED, PA/OA-ED) or a normal-standard diet (n=12/group) for 16 weeks and were orally infected with /placebo to induce periodontal disease. Using histomorphometry and LC-MS/MS, systemic bone morphology, incorporated immunometabolic FA-species, serological markers of bone metabolism, and stress response were determined in addition to bone cell inflammation and interaction .
RESULTS
In contrast to OA-ED, PA-ED reduced systemic bone microarchitecture paralleled by increased lipotoxic PA-containing metabolite accumulation in bone. Substitution with OA reversed the bone-destructive impact of PA, which was accompanied by reduced diacylglycerols (DAG) and saturated ceramide levels. Further, PA-associated reduction in mineralization activity and concomitant pro-inflammatory activation of primary osteoblasts were diminished in cultures where PA was replaced with OA, which impacted cellular interaction with osteoclasts. Additionally, PA-ED increased osteoclast numbers in femurs in response to oral infection, whereas OA-ED reduced osteoclast occurrence, which was paralleled by serologically increased levels of the stress-reducing lipokine PI(18:1/18:1).
CONCLUSION
OA substitution reverses the bone-destructive and pro-inflammatory effects of PA and eliminates incorporated lipotoxic PA metabolites. This supports Mediterranean-style OA-based diets as a preventive intervention to target the accumulation of PA-associated lipotoxic metabolites and thereby supports systemic bone tissue resilience after oral bacterial infection.
Topics: Mice; Humans; Animals; Mice, Inbred C57BL; Fatty Acids; Chromatography, Liquid; Tandem Mass Spectrometry; Periodontitis; Bone and Bones; Periodontal Diseases; Inflammation; Cell Communication
PubMed: 37736098
DOI: 10.3389/fimmu.2023.1213026 -
International Journal of Genomics 2023Genome-wide association studies (GWAS) are a powerful tool for identifying genomic regions and causative genes associated with economically important traits in dairy... (Review)
Review
Genome-wide association studies (GWAS) are a powerful tool for identifying genomic regions and causative genes associated with economically important traits in dairy cattle, particularly complex traits, such as milk production. This is possible due to advances in next-generation sequencing technology. This review summarized information on identified candidate genes and genomic regions associated with milk production traits in Holstein and its crossbreds from various regions of the world. Milk production traits are important in dairy cattle breeding programs because of their direct economic impact on the industry and their close relationship with nutritional requirements. GWAS has been used in a large number of studies to identify genomic regions and candidate genes associated with milk production traits in dairy cattle. Many genomic regions and candidate genes have already been identified in Holstein and its crossbreds. Genes and single nucleotide polymorphisms (SNPs) that significantly affect milk yield (MY) were found in all autosomal chromosomes except chromosomes 27 and 29. Half of the reported SNPs associated with fat yield and fat percentage were found on chromosome 14. However, a large number of significant SNPs for protein yield (PY) and protein percentage were found on chromosomes 1, 5, and 20. Approximately 155 SNPs with significant influence on multiple milk production traits have been identified. Several promising candidate genes, including diacylglycerol O-acyltransferase 1, plectin, Rho GTPase activating protein 39, protein phosphatase 1 regulatory subunit 16A, and sphingomyelin phosphodiesterase 5 were found to have pleiotropic effects on all five milk production traits. Thus, to improve milk production traits it is of practical relevance to focus on significant SNPs and pleiotropic genes frequently found to affect multiple milk production traits.
PubMed: 37547753
DOI: 10.1155/2023/8497453 -
Public Health Nutrition Nov 2023Ultra-processed foods (UPF), including those containing food additive emulsifiers, have received research attention due to evidence implicating them in the pathogenesis...
OBJECTIVE
Ultra-processed foods (UPF), including those containing food additive emulsifiers, have received research attention due to evidence implicating them in the pathogenesis of certain diseases. The aims of this research were to develop a large-scale, brand-level database of UPF in the UK food supply and to characterise the occurrence and co-occurrence of food additive emulsifiers.
DESIGN
A database was compiled sampling all products from the food categories contributing to energy intake from UPF in the UK from the National Diet and Nutrition Survey (2008-2014). Every food in these categories were identified from online supermarket provision from the 'big four' supermarkets that dominate the market share in the UK, comprising Tesco, Sainsbury's, Asda and Morrisons.
SETTING
Major supermarkets in the UK.
RESULTS
A total of 32 719 food products in the UK supermarket food supply were returned in searches. Of these, 12 844 products were eligible and manually reviewed for the presence of emulsifiers. Emulsifiers were present in 6642 (51·7 %) food products. Emulsifiers were contained in 95·0 % of 'Pastries, buns and cakes', 81·9 % of 'Milk-based drinks', 81·0 % of 'Industrial desserts' and 77·5 % of 'Confectionary'. Fifty-one per cent of all emulsifier-containing foods contained multiple emulsifiers. Across emulsifier-containing foods, there were a median of two emulsifiers (IQR 2) per product. The five most common emulsifiers were lecithin (23·4 % of all products), mono- and diglycerides of fatty acids (14·5 %), diphosphates (11·6 %), and xanthan gum and pectin (8·0 %).
CONCLUSIONS
Findings from this study are the first to demonstrate the widespread occurrence and co-occurrence of emulsifiers in UPF in the UK food supply.
Topics: Humans; Food, Processed; Fast Foods; Food Handling; Diet; Food Additives; Food Supply; United Kingdom; Food
PubMed: 37732384
DOI: 10.1017/S1368980023002021 -
Microbiology Spectrum Sep 2023Lysyl-diacylglycerol (Lys-DAG) was identified three decades ago in , but the biosynthetic pathway and function of this aminoacylated lipid have since remained...
Lysyl-diacylglycerol (Lys-DAG) was identified three decades ago in , but the biosynthetic pathway and function of this aminoacylated lipid have since remained uncharacterized. Combining genetic methods, mass spectrometry, and biochemical approaches, we show that the multiple peptide resistance factor (MprF) homolog LysX from and two mycobacterial species is responsible for Lys-DAG synthesis. LysX is conserved in most Actinobacteria and was previously implicated in the synthesis of another modified lipid, lysyl-phosphatidylglycerol (Lys-PG), in . Although we detected low levels of Lys-PG in the membrane of , our data suggest that Lys-PG is not directly synthesized by LysX and may require an additional downstream pathway, which is as yet undefined. Our results show that LysX in is a major factor of resistance against a variety of positively charged antibacterial agents, including cationic antimicrobial peptides (e.g., human peptide LL-37 and polymyxin B) and aminoglycosides (e.g., gentamycin and apramycin). Deletion of caused an increase in cellular membrane permeability without dissipation of the membrane potential, suggesting that loss of the protein does not result in mechanical damage to the cell membrane. Furthermore, -deficient cells exhibited an attenuated virulence phenotype in a infection model, supporting a role for LysX during infection. Altogether, Lys-DAG represents a novel molecular determinant for antimicrobial resistance and virulence that may be widespread in Actinobacteria and points to a richer landscape than previously realized of lipid components contributing to overall membrane physiology in this important bacterial phylum. IMPORTANCE In the past two decades, tRNA-dependent modification of membrane phosphatidylglycerol has been implicated in altering the biochemical properties of the cell surface, thereby enhancing the antimicrobial resistance and virulence of various bacterial pathogens. Here, we show that in several Actinobacteria, the multifunctional protein LysX attaches lysine to diacylglycerol instead of phosphatidylglycerol. We found that lysyl-diacylglycerol (Lys-DAG) confers high levels of resistance against various cationic antimicrobial peptides and aminoglycosides and also enhances virulence. Our data show that Lys-DAG is a lipid commonly found in important actinobacterial pathogens, including and species.
PubMed: 37768052
DOI: 10.1128/spectrum.01429-23 -
Frontiers in Endocrinology 2023Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as "forever chemicals" due to...
INTRODUCTION
Multiple factors can contribute to sub-fecundity, including genetics, lifestyle, and environmental contaminants. PFASs are characterized as "forever chemicals" due to their ubiquitous contamination and their persistence in the environment, wildlife, and humans. Numerous studies have demonstrated that PFAS exposure adversely affects multiple bodily functions, including liver metabolism and gonadal function. It is unclear, however, how the disruption of hepatic fatty acid metabolism affects testicular function.
METHODS
In this study, male mice were administered 0.3 and 3 μg/g body weight of PFOS for 21 days.
RESULTS
Our data showed that PFOS exposure caused hepatic steatosis, as evidenced by significant increases in triglyceride levels, expression of ATP-citrate lyase, and fatty acid synthase, as well as fasting insulin levels. PFOS perturbed the expression levels of hepatokines, of which fibroblast growth factor-21 (), leukocyte cell-derived chemotaxin-2 (), and retinol-binding protein-4 () were significantly reduced, whereas angiopoietin-like 4 () was noticeably increased. While are known to contribute to spermatogenesis and testosterone synthesis. In PFOS-exposed groups, testicular ATP, and testosterone decreased significantly with a significant increase in the expression of peroxisome proliferator-activated receptor-coactivator 1α. Mass spectrophotometry imaging revealed the localization of PFOS in testes, along with significant increases in fatty acid metabolites. These included arachidonic acid, dihomo-α-linolenic acid, dihomo-γ-linolenic acid, oxidized ceramide, diacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, which are associated with inflammation and post-testicular causes of infertility.
DISCUSSION
This study revealed potential links between PFOS-elicited changes in hepatic metabolism and their impacts on testicular biology. This study provides insights into alternative targets elicited by PFOS that can be used to develop diagnostic and therapeutic strategies for improving testicular dysfunction.
Topics: Humans; Mice; Male; Animals; Testis; Fatty Acids; Liver; Testosterone; Adenosine Triphosphate
PubMed: 38075064
DOI: 10.3389/fendo.2023.1302965 -
Metabolites Aug 2023ANGPTL8 is recognized as a regulator of lipid metabolism through its role in inhibiting lipoprotein lipase activity. ANGPTL8 gene variants, particularly rs2278426...
ANGPTL8 is recognized as a regulator of lipid metabolism through its role in inhibiting lipoprotein lipase activity. ANGPTL8 gene variants, particularly rs2278426 leading to the R59W variant in the protein, have been associated with lipid traits in various ethnicities. We aimed to use metabolomics to understand the impact of the ANGPTL8 R59W variant on metabolites in humans. We used the Biocrates-p400 kit to quantify 408 plasma metabolites in 60 adult male Arab individuals from Kuwait and identify differences in metabolite levels between individuals carrying reference genotypes and those with carrier genotypes at ANGPTL8 rs2278426. Individuals with carrier genotypes (CT+TT) compared to those carrying the reference genotype (CC) showed statistically significant differences in the following metabolites: acylcarnitine (perturbs metabolic pathways), phosphatidylcholine (supports liver function and cholesterol levels), cholesteryl ester (brings chronic inflammatory response to lipoprotein depositions in arteries), α-aminoadipic acid (modulates glucose homeostasis), histamine (regulates glucose/lipid metabolism), sarcosine (links amino acid and lipid metabolism), diacylglycerol 42:1 (regulates homeostasis of cellular lipid stores), and lysophosphatidylcholine (regulates oxidative stress and inflammatory response). Functional aspects attributed to these metabolites indicate that the ANGPTL8 R59W variant influences the concentrations of lipid- and inflammation-related metabolites. This observation further highlights the role of ANGPTL8 in lipid metabolism.
PubMed: 37755252
DOI: 10.3390/metabo13090972 -
Food Science and Biotechnology Nov 2023Lipid oxidation is one of the key chemical reactions in foods containing fats and oils during production and storage. For several decades, many researchers have tried to... (Review)
Review
Lipid oxidation is one of the key chemical reactions in foods containing fats and oils during production and storage. For several decades, many researchers have tried to understand the mechanisms of lipid oxidation and ways to control the rates of lipid oxidation. Theories of autoxidation or free radical chain reaction have been developed to successfully explain the phenomenon observed in oxidized lipids. Many studies have been conducted to explain the other factors that can affect the lipid oxidation such as food matrix, oxidation time and temperature, transition metal ions, pigments with sensitizing abilities, and surface-active compounds such as phospholipids, free fatty acids, monoacylglycerols, and diacylglycerols. Several strategies were developed to evaluate the degree of oxidation and oxidative stability. This review provides crucial information on the mechanism of lipid oxidation affected amphiphilic compounds and association colloids. This review article will extensively discuss about the methods for determining the oxidative stability.
PubMed: 37781049
DOI: 10.1007/s10068-023-01359-1