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Nature Sep 2015Mitochondria are involved in a variety of cellular functions, including ATP production, amino acid and lipid biogenesis and breakdown, signalling and apoptosis....
Mitochondria are involved in a variety of cellular functions, including ATP production, amino acid and lipid biogenesis and breakdown, signalling and apoptosis. Mitochondrial dysfunction has been linked to neurodegenerative diseases, cancer and ageing. Although transcriptional mechanisms that regulate mitochondrial abundance are known, comparatively little is known about how mitochondrial function is regulated. Here we identify the metabolite stearic acid (C18:0) and human transferrin receptor 1 (TFR1; also known as TFRC) as mitochondrial regulators. We elucidate a signalling pathway whereby C18:0 stearoylates TFR1, thereby inhibiting its activation of JNK signalling. This leads to reduced ubiquitination of mitofusin via HUWE1, thereby promoting mitochondrial fusion and function. We find that animal cells are poised to respond to both increases and decreases in C18:0 levels, with increased C18:0 dietary intake boosting mitochondrial fusion in vivo. Intriguingly, dietary C18:0 supplementation can counteract the mitochondrial dysfunction caused by genetic defects such as loss of the Parkinson's disease genes Pink or Parkin in Drosophila. This work identifies the metabolite C18:0 as a signalling molecule regulating mitochondrial function in response to diet.
Topics: Acetyltransferases; Animals; Antigens, CD; Diet; Drosophila Proteins; Drosophila melanogaster; Fatty Acid Elongases; HeLa Cells; Humans; JNK Mitogen-Activated Protein Kinases; Larva; Membrane Proteins; Mitochondria; Mitochondrial Dynamics; Receptors, Transferrin; Signal Transduction; Stearic Acids; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Ubiquitination
PubMed: 26214738
DOI: 10.1038/nature14601 -
Journal of Dairy Science 2014Energy is the most limiting nutritional component in diets for high-producing dairy cows. Palmitic (C16:0) and stearic (C18:0) acids have unique and specific functions... (Review)
Review
Energy is the most limiting nutritional component in diets for high-producing dairy cows. Palmitic (C16:0) and stearic (C18:0) acids have unique and specific functions in lactating dairy cows beyond a ubiquitous energy source. This review delineates their metabolism and usage in lactating dairy cows from diet to milk production. Palmitic acid is the fatty acid (FA) found in the greatest quantity in milk fat. Dietary sources of C16:0 generally increase milk fat yield and are used as an energy source for milk production and replenishing body weight loss during periods of negative energy balance. Stearic acid is the most abundant FA available to the dairy cow and is used to a greater extent for milk production and energy balance than C16:0. However, C18:0 is also intimately involved in milk fat production. Quantifying the transfer of each FA from diet into milk fat is complicated by de novo synthesis of C16:0 and desaturation of C18:0 to oleic acid in the mammary gland. In addition, incorporation of both FA into milk fat appears to be limited by the cow's requirement to maintain fluidity of milk, which requires a balance between saturated and unsaturated FA. Oleic acid is the second most abundant FA in milk fat and likely the main unsaturated FA involved in regulating fluidity of milk. Because the mammary gland can desaturate C18:0 to oleic acid, C18:0 appears to have a more prominent role in milk production than C16:0. To understand metabolism and utilization of these FA in lactating dairy cows, we reviewed production and milk fat synthesis studies. Additional and longer lactation studies on feeding both FA to lactating dairy cows are required to better delineate their roles in optimizing milk production and milk FA composition and yield.
Topics: Animals; Cattle; Diet; Dietary Fats; Digestion; Duodenum; Female; Lactation; Milk; Oleic Acid; Palmitic Acid; Stearic Acids; Triglycerides
PubMed: 24913651
DOI: 10.3168/jds.2014-7919 -
British Journal of Cancer Oct 1987Decreased membrane rigidity is one of the characteristics of malignant cells, resulting in part from the desaturation of stearic acid into oleic acid. In this study we...
Decreased membrane rigidity is one of the characteristics of malignant cells, resulting in part from the desaturation of stearic acid into oleic acid. In this study we investigated the influence of stearic acid on tumour cell inhibition in vitro and tumour development in vivo. Stearic acid inhibited the colony-forming ability of 4 out of 5 rat and two human tumour continuous cell lines in vitro. In contrast, the colony-forming ability of rat fibroblasts was not inhibited and that of human foetal lung fibroblasts was inhibited at a higher dose than that required to inhibit human tumour cell lines. Using a model of rat mammary carcinoma induced by nitroso-methyl urea (NMU) the subcutaneous injection of stearic acid at weekly intervals prevented tumour development in 5 to 10 rats. Using iodostearic acid twice weekly, 11 of 19 rats were alive and tumour free at week 22 whilst all of 14 animals injected with NMU alone had died of tumour by the 16th week. The ratio of stearic to oleic acids in erythrocyte membranes was significantly reduced in the tumour-bearing rats, but was normal in tumour-free animals treated with stearic or iodostearic acid. These preliminary data indicate that stearic acid inhibits tumour development in rats.
Topics: Animals; Antineoplastic Agents; Cell Line; Dose-Response Relationship, Drug; Erythrocytes; Fibroblasts; Liver Neoplasms, Experimental; Mammary Neoplasms, Experimental; Oleic Acid; Oleic Acids; Rats; Rats, Inbred Strains; Stearic Acids; Tumor Cells, Cultured; Tumor Stem Cell Assay
PubMed: 3689663
DOI: 10.1038/bjc.1987.223 -
Journal of Oleo Science Aug 2023Lycopene is a natural bioactive compound possessing higher antioxidant and anti-inflammatory properties, which are known to efficiently eliminate the risk of cancer,...
Lycopene is a natural bioactive compound possessing higher antioxidant and anti-inflammatory properties, which are known to efficiently eliminate the risk of cancer, cardiac complications, and oxidative stress. Food manufacturers are keen on producing lycopene-fortified food products owing to their numerous health benefits and higher nutritional value. The incorporation of lycopene is limited to food products due to its hydrophobic nature and low chemical stability. This study aims to understand the incorporation of lycopene in Oleogel as a new delivery system. Briefly, lycopene and stearic acid (gelator) were combined at ratios of 0, 25, 50, 75, and 100% (w/w) and added to coconut oil (20 g (w/w) ) for the preparation of edible oleogel combinations. These combinations were characterized for oil binding capacity, swelling capacity, color analysis, and texture profile analysis. Further, the formulations were characterized by FTIR (Fourier Transform Infrared Spectroscopy) and DSC (Differential scanning calorimetry). It was observed that samples prepared with a combination of 50% lycopene and stearic acid were found to possess a firm texture and good stability. Conversely, samples with no gelator produced oleogels with less stability. Further, the FTIR spectra helped determine the network formation in the oleogels, which was stabilized by the hydrogen bond. Furthermore, the results of DSC exhibited that the oleogel combinations with gelator and lycopene were not in the crystalline state, and the oleogels held superior internal structure till 45°C. Overall, oleogel-based carrier systems can be used as an alternative method to encapsulate various bioactive compounds having possible potential applications in the bakery and confectionery industries.
Topics: Coconut Oil; Lycopene; Stearic Acids
PubMed: 37468274
DOI: 10.5650/jos.ess22398 -
Arquivos Brasileiros de Cardiologia 2023Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused...
BACKGROUND
Several studies have associated dietary saturated fatty acids (SFAs) with cardiovascular risk but there are still many controversies. Most of these studies have focused on the effects of palmitic acid on circulating lipids. Stearic acid usually shows a neutral effect on blood lipids, however, there is a lack of clinical studies assessing the link with inflammatory and endothelial dysfunction markers.
OBJECTIVE
To evaluate the association of red blood cell (RBC) SFA (palmitic and stearic acids) with circulating inflammatory and endothelial dysfunction biomarkers.
METHODS
Cross-sectional study of 79 adults of both sexes with at least one cardiovascular risk factor but without previous events (acute myocardial infarction or stroke). Plasma biomarkers - lipids, glucometabolic markers, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-α (TNF-α) - and RBC palmitic and stearic fatty acids were analyzed. The associations were assessed by correlation and multiple linear regression analyses, with statistical significance set at p < 0.05.
RESULTS
Palmitic acid showed no significant associations with traditional cardiovascular risk factors or inflammatory markers. Stearic acid, on the other hand, was inversely correlated with blood cholesterol and triglycerides, but independently associated with hs-CRP, IL-6, and TNF-α.
CONCLUSION
Stearic acid is associated with inflammatory and endothelial dysfunction biomarkers in individuals with at least one cardiovascular risk factor.
Topics: Adult; Female; Male; Humans; Palmitic Acid; C-Reactive Protein; Cardiovascular Diseases; Cross-Sectional Studies; Interleukin-6; Tumor Necrosis Factor-alpha; Risk Factors; Stearic Acids; Biomarkers; Stroke; Heart Disease Risk Factors
PubMed: 37672472
DOI: 10.36660/abc.20220598 -
Traffic (Copenhagen, Denmark) Feb 2022Cell polarity is achieved by regulators such as small G proteins, exocyst members and phosphoinositides, with the latter playing a key role when bound to the exocyst...
Cell polarity is achieved by regulators such as small G proteins, exocyst members and phosphoinositides, with the latter playing a key role when bound to the exocyst proteins Sec3p and Exo70p, and Rho GTPases. This ensures asymmetric growth via the routing of proteins and lipids to the cell surface using actin cables. Previously, using a yeast mutant for a lysophosphatidylinositol acyl transferase encoded by the PSI1 gene, we demonstrated the role of stearic acid in the acyl chain of phosphoinositides in cytoskeletal organization and secretion. Here, we use a genetic approach to characterize the effect on late steps of the secretory pathway. The constitutive overexpression of PSI1 in mutants affecting kinases involved in the phosphoinositide pathway demonstrated the role of molecular species containing stearic acid in bypassing a lack of phosphatidylinositol-4-phosphate (PI(4)P) at the plasma membrane, which is essential for the function of the Cdc42p module. Decreasing the levels of stearic acid-containing phosphoinositides modifies the environment of the actors involved in the control of late steps in the secretory pathway. This leads to decreased interactions between Exo70p and Sec3p, with Cdc42p, Rho1p and Rho3p, because of disruption of the GTP/GDP ratio of at least Rho1p and Rho3p GTPases, thereby preventing activation of the exocyst.
Topics: Exocytosis; Phosphatidylinositols; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Stearic Acids; Vesicular Transport Proteins; rho GTP-Binding Proteins
PubMed: 34908215
DOI: 10.1111/tra.12829 -
Nutrition Research Reviews Jun 2009The position of fatty acids in the TAG molecule (sn-1, sn-2 and sn-3) determines the physical properties of the fat, which affects its absorption, metabolism and... (Review)
Review
The position of fatty acids in the TAG molecule (sn-1, sn-2 and sn-3) determines the physical properties of the fat, which affects its absorption, metabolism and distribution into tissues, which may have implications for the risk of CHD. The TAG structure of fats can be manipulated by the process of interesterification, which is of increasing commercial importance, as it can be used to change the physical characteristics of a fat without the generation of trans-fatty acids. Interesterified fats rich in long-chain SFA are commercially important, but few studies have investigated their health effects. Evidence from animal and human infant studies suggests that TAG structure and interesterification affect digestibility, atherogenicity and fasting lipid levels, with fats containing palmitic and stearic acid in the sn-2 position being better digested and considered to be more atherogenic. However, chronic studies in human adults suggest that TAG structure has no effect on digestibility or fasting lipids. The postprandial effects of fats with differing TAG structure are better characterised but the evidence is inconclusive; it is probable that differences in the physical characteristics of fats resulting from interesterification and changes in TAG structure are key determinants of the level of postprandial lipaemia, rather than the position of fatty acids in the TAG. The present review gives an overview of TAG structure and interesterified palmitic and stearic acid-rich fats, their physical properties and their acute and chronic effects in human adults in relation to CHD.
Topics: Adult; Animals; Coronary Disease; Diet, Atherogenic; Dietary Fats; Esterification; Humans; Hyperlipidemias; Infant; Lipid Metabolism; Lipids; Palmitic Acid; Plant Oils; Stearic Acids; Trans Fatty Acids; Triglycerides
PubMed: 19442321
DOI: 10.1017/S0954422409369267 -
International Journal of Nanomedicine 2022This study aimed to design a prototypic drug delivery system (DDS) made of an amphiphilic, pullulan (Pull)-derived biodegradable polymer for targeting the...
PURPOSE
This study aimed to design a prototypic drug delivery system (DDS) made of an amphiphilic, pullulan (Pull)-derived biodegradable polymer for targeting the asialoglycoprotein receptor (ASGPR) overexpressed in HCC. Stearic acid (SA) was conjugated to increase the hydrophobicity of pullulan (Pull-SA).
METHODS
Pullulan (Pull) was linked to stearic acid (SA) after functional group modifications via EDC/NHS chemistry and characterized. Sorafenib tosylate (SRFT) was entrapped in pullulan-stearic acid nanoparticles (Pull-SA-SRFT) and its particle size, zeta potential, entrapment efficiency (EE), loading capacity (LC), and release efficiency was measured. The competence of Pull-SA-SRFT over SRFT in vitro was assessed using the ASGPR over-expressing PLC/PRF/5 hepatocellular carcinoma (HCC) cell line. This was done by studying cytotoxicity by MTT assay and chromosome condensation assay, early apoptosis by annexin-Pi staining, and late apoptosis by live-dead assay. The cellular uptake study was performed by incorporating coumarin-6 (C6) fluorophore in place of SRFT in Pull-SA conjugates. A biodistribution study was conducted in Swiss-albino mice to assess the biocompatibility and targeting properties of SRFT and Pull-SA-SRFT to the liver and other organs at 1, 6, 24, and 48 h.
RESULTS
The characterization studies of the copolymer confirmed the successful conjugation of Pull-SA. The self-assembled amphiphilic nanocarrier could proficiently entrap the hydrophobic drug SRFT to obtain an entrapment efficiency of 95.6% (Pull-SA-SRFT). Characterization of the synthesized nanoparticles exhibited highly desirable nanoparticle characteristics. In vitro, apoptotic studies urged that Pull-SA-SRFT nanoparticle was delivered more efficiently to HCC than SRFT. The cellular uptake study performed, gave propitious results in 4 hrs. The biodistribution study conducted in immunocompetent mice suggested that Pull-SA-SRFT was delivered more than SRFT to the liver when compared to other organs, and that the system was biocompatible.
CONCLUSION
Pull-SA-SRFT is a promisingly safe, biodegradable, cell-specific nanocarrier and a potential candidate to target hydrophobic drugs to HCC.
Topics: Mice; Animals; Carcinoma, Hepatocellular; Sorafenib; Tissue Distribution; Liver Neoplasms; Glucans; Asialoglycoprotein Receptor; Nanoparticles; Drug Delivery Systems; Drug Carriers; Antineoplastic Agents
PubMed: 36340185
DOI: 10.2147/IJN.S377354 -
Bioengineered Dec 2021Chronic exposure to high concentrations of circulating palmitic acid and stearic acid leads to impaired β cell function, which accelerates the development of type 2...
Comparative analysis of circRNA expression profile and circRNA-miRNA-mRNA regulatory network between palmitic and stearic acid-induced lipotoxicity to pancreatic β cells.
Chronic exposure to high concentrations of circulating palmitic acid and stearic acid leads to impaired β cell function, which accelerates the development of type 2 diabetes. However, differences in the mechanisms underlying this process between these two saturated fatty acids remain largely unknown. In this study, we screened for potential circular RNAs (circRNAs) and their associated regulatory pathways in palmitic acid- and stearic acid-induced mouse β-TC6 cell dysfunction. CircRNA high-throughput sequencing, gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes analysis were performed and co-expression and competing endogenous RNAs (ceRNA) networks were constructed. We identified that four circRNAs that were differentially expressed specifically in β cells exposed to palmitic acid, whereas four circRNAs were differentially expressed specifically in β cells exposed to stearic acid. Seven circRNAs were differentially co-expressed in palmitic acid- and stearic acid-treated β cells. In pathway exploration, we identified the core protein Solute carrier family 2 member 2 (SLc2a2), which is mainly involved in insulin resistance, maturity onset diabetes of the young and type 2 diabetes. The expressions of key circRNAs in β-TC6 cells were validated by Real time quantitative PCR, with a consistent result in high-throughput sequencing. The findings aid our understanding of the mechanisms governing the difference between palmitic acid- and stearic acid-induced β cell dysfunction and provide potential therapeutic targets for developing treatments against long-term high fat diet-induced β cell injury. Acvr1c: Activin A receptor, type 1C; CeRNA, Competing endogenous RNAs; circRNA, circular RNA; DEcircRNA: Differentially Expressed circular RNA; DEmiRNA: Differentially Expressed microRNA; DEmRNA: Differentially Expressed mRNA; GO: Gene Ontology; HPDHigh Palmitic acid Diet; HSD: High Stearic acid Diet; KEGG: Kyoto Encyclopedia of Genes and Genomes; miRNA: microRNA; ncRNAs: non-coding RNAs; qPCR: Real time quantitative PCRS; FAs: Saturated Fatty Acids; SLc2a2: Solute carrier family 2 member 2; T2D: Type 2 Diabetes.
Topics: Animals; Gene Expression Profiling; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; High-Throughput Nucleotide Sequencing; Insulin-Secreting Cells; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Palmitic Acid; RNA, Circular; RNA, Messenger; Stearic Acids
PubMed: 34654356
DOI: 10.1080/21655979.2021.1992333 -
International Journal of Nanomedicine 2012Both polymer micelles and mesoporous silica nanoparticles have been widely researched as vectors for small molecular insoluble drugs. To combine the advantages of...
PURPOSE
Both polymer micelles and mesoporous silica nanoparticles have been widely researched as vectors for small molecular insoluble drugs. To combine the advantages of copolymers and silica, studies on the preparation of copolymer-silica composites and cellular evaluation were carried out.
METHODS
First, a stearic acid-g-chitosan (CS-SA) copolymer was synthesized through a coupling reaction, and then silicone oxide (SiO(2))-deposited doxorubicin (DOX)-loaded stearic acid-g-chitosan (CS-SA/SiO(2)/DOX) nanoparticles were prepared through the sol-gel reaction. Physical and chemical properties such as particle size, zeta potential, and morphologies were examined, and small-angle X-ray scattering (SAXS) analysis was employed to identify the mesoporous structures of the generated nanoparticles. Cellular uptake and cytotoxicity studies were also conducted.
RESULTS
CS-SA/SiO(2)/DOX nanoparticles with different amounts of SiO(2) deposited were obtained, and SAXS studies showed that mesoporous structures existed in the CS-SA/SiO(2)/DOX nanoparticles. The mesoporous size of middle-ratio and high-ratio deposited CS-SA/SiO(2)/DOX nanoparticles were 4-5 nm and 8-10 nm, respectively. Based on transmission electron microscopy images of CS-SA/SiO(2)/DOX nanoparticles, dark rings around the nanoparticles could be observed in contrast with CS-SA/DOX micelles. Furthermore, CS-SA/SiO(2)/DOX nanoparticles exhibited faster release behavior in vitro than CS-SA/DOX micelles; cellular uptake research in A549 indicated that the CS-SA/SiO(2)/DOX nanoparticles were taken up by A549 cells more rapidly, and that CS-SA/SiO(2)/DOX nanoparticles entered the cell more easily when the amount of SiO(2) was higher. IC(50) values of CS-SA/DOX micelles, CS-SA/SiO(2)/DOX-4, CS-SA/SiO(2)/DOX-8, and CS-SA/SiO(2)/DOX-16 nanoparticles against A549 cells measured using the MTT assay were 1.69, 0.93, 0.32, and 0.12 μg/mL, respectively.
CONCLUSION
SiO(2)-deposited stearic acid-g-chitosan organic-inorganic composites show promise as nanocarriers for hydrophobic drugs such as DOX.
Topics: Adsorption; Cell Line, Tumor; Chitosan; Diffusion; Doxorubicin; Humans; Lung Neoplasms; Nanocapsules; Silicon Dioxide; Stearic Acids
PubMed: 23055724
DOI: 10.2147/IJN.S35575