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Molecular Biology Reports Dec 2020Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the...
Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the pathogenesis of insulin resistance. Lauric acid is a 12-carbon medium chain fatty acid (MCFA) found abundantly in coconut oil or palm kernel oil and it comes with multiple beneficial effects. This research objective was to uncover the effects of the lauric acid on glucose uptake, mitochondrial function and mitochondrial biogenesis in insulin-resistant macrophages. THP-1 monocytes were differentiated into macrophages and induce insulin resistance, before they were treated with increasing doses of lauric acid (5 μM, 10 μM, 20 μM, and 50 μM). Glucose uptake assay, cellular ROS and ATP production assays, mitochondrial content and membrane potential assay were carried out to analyse the effects of lauric acid on insulin resistance and mitochondrial biogenesis in the macrophages. Quantitative RT-PCR (qRT-PCR) and western blot analysis were also performed to determine the expression of the key regulators. Insulin-resistant macrophages showed lower glucose uptake, GLUT-1 and GLUT-3 expression, and increased hallmarks of mitochondrial dysfunction. Interestingly, lauric acid treatment upregulated glucose uptake, GLUT-1 and GLUT-3 expressions. The treatment also restored the mitochondrial biogenesis in the insulin-resistant macrophages by improving ATP production, oxygen consumption, mitochondrial content and potential, while it promoted the expression of mitochondrial biogenesis regulator genes such as TFAM, PGC-1α and PPAR-γ. We show here that lauric acid has the potential to improve insulin sensitivity and mitochondrial dysregulation in insulin-resistant macrophages.
Topics: Adenosine Triphosphate; Biological Transport; Cell Differentiation; DNA-Binding Proteins; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 3; Humans; Hypoglycemic Agents; Insulin Resistance; Lauric Acids; Macrophages; Mitochondria; Mitochondrial Proteins; Organelle Biogenesis; PPAR gamma; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Reactive Oxygen Species; THP-1 Cells; Tetradecanoylphorbol Acetate; Transcription Factors
PubMed: 33259010
DOI: 10.1007/s11033-020-06019-9 -
Food and Chemical Toxicology : An... Jul 2020
Review
Topics: Humans; Lauric Acids; Odorants; Perfume; Toxicity Tests
PubMed: 32389839
DOI: 10.1016/j.fct.2020.111383 -
Toxicology and Applied Pharmacology Jul 2023Lauric acid, a 12‑carbon atom medium chain fatty acid (MCFA) has strong antioxidant and antidiabetic activities. However, whether lauric acid can ameliorate...
Lauric acid improves hormonal profiles, antioxidant properties, sperm quality and histomorphometric changes in testis and epididymis of streptozotocin-induced diabetic infertility rats.
Lauric acid, a 12‑carbon atom medium chain fatty acid (MCFA) has strong antioxidant and antidiabetic activities. However, whether lauric acid can ameliorate hyperglycaemia-induced male reproductive damage remains unclear. The study aimed to determine the optimal dose of lauric acid with glucose-lowering activity, antioxidant potential and tissue-protective effects on the testis and epididymis of streptozotocin (STZ)-induced diabetic rats. Hyperglycaemia was induced in Sprague Dawley rats by an intravenous injection of STZ at a dose of 40 mg/kg body weight (bwt). Lauric acid (25, 50 and 100 mg/kg bwt) was administered orally for eight weeks. Weekly fasting blood glucose (FBG), glucose tolerance and insulin sensitivity were examined. Hormonal profiles (insulin and testosterone), lipid peroxidation (MDA) and antioxidant enzyme (SOD and CAT) activities were measured in the serum, testis and epididymis. The reproductive analyses were evaluated based on sperm quality and histomorphometry. Lauric acid administration significantly improved FBG levels, glucose tolerance, hormones-related fertility and oxidant-antioxidant balance in the serum, testis and epididymis compared to untreated diabetic rats. Treatment with lauric acid preserved the testicular and epididymal histomorphometry, along with the significant improvements in sperm characteristics. It is shown for the first time that lauric acid treatment at 50 mg/kg bwt is the optimal dose for ameliorating hyperglycaemia-induced male reproductive complications. We conclude that lauric acid reduced hyperglycaemia by restoring insulin and glucose homeostasis, which attributes to the regeneration of tissue damage and sperm quality in STZ-induced diabetic rats. These findings support the correlation between oxidative stress and hyperglycaemia-induced male reproductive dysfunctions.
Topics: Humans; Male; Rats; Animals; Testis; Antioxidants; Epididymis; Streptozocin; Diabetes Mellitus, Experimental; Rats, Wistar; Rats, Sprague-Dawley; Semen; Spermatozoa; Oxidative Stress; Infertility, Male; Hyperglycemia; Glucose; Insulins
PubMed: 37211320
DOI: 10.1016/j.taap.2023.116558 -
Food Chemistry Aug 2022Four types of pure lipid, namely lauric acid (LA), glycerol monolaurate (MAG), diglycerol laurate (DAG) and triglyceride laurate (TAG) were used to prepare oleofoams....
Four types of pure lipid, namely lauric acid (LA), glycerol monolaurate (MAG), diglycerol laurate (DAG) and triglyceride laurate (TAG) were used to prepare oleofoams. The relationship between crystal profiles and their performance in oleofoams was established. DAG formed small needle-like crystals while MAG formed large flake-like crystals in oleogels, and crystal shells around air bubbles were observed in LA-, MAG- and DAG-based oleofoams. LA and DAG displayed higher over-run whereas DAG-stabilised foam possessed smaller bubbles and higher physical stability due to the presence of small β and β' crystals. Upon heating, DAG and TAG-based foams showed varying extents of oil drainage indicating the crystals were distributed in a different manner. Therefore, DAG was shown to be an excellent gelator in the fabrication of ultra-stable oleofoams. This work extends the lipid varieties with nutritional features and allows a better understanding on the stabilization mechanisms of lauric acid lipids in oleofoams.
Topics: Diglycerides; Esters; Glycerol; Laurates; Lauric Acids
PubMed: 35509162
DOI: 10.1016/j.foodchem.2022.132776 -
Journal of Microbiology and... Jan 2021Persister cell formation and biofilms of pathogens are extensively involved in the development of chronic infectious diseases. Eradicating persister cells is...
Persister cell formation and biofilms of pathogens are extensively involved in the development of chronic infectious diseases. Eradicating persister cells is challenging, owing to their tolerance to conventional antibiotics, which cannot kill cells in a metabolically dormant state. A high frequency of persisters in biofilms makes inactivating biofilm cells more difficult, because the biofilm matrix inhibits antibiotic penetration. Fatty acids may be promising candidates as antipersister or antibiofilm agents, because some fatty acids exhibit antimicrobial effects. We previously reported that fatty acid ethyl esters effectively inhibit persister formation by regulating an antitoxin. In this study, we screened a fatty acid library consisting of 65 different fatty acid molecules for altered persister formation. We found that undecanoic acid, lauric acid, and N-tridecanoic acid inhibited BW25113 persister cell formation by 25-, 58-, and 44-fold, respectively. Similarly, these fatty acids repressed persisters of enterohemorrhagic EDL933. These fatty acids were all medium-chain saturated forms. Furthermore, the fatty acids repressed Enterohemorrhagic (EHEC) biofilm formation (for example, by 8-fold for lauric acid) without having antimicrobial activity. This study demonstrates that medium-chain saturated fatty acids can serve as antipersister and antibiofilm agents that may be applied to treat bacterial infections.
Topics: Anti-Bacterial Agents; Bacterial Infections; Biofilms; Escherichia coli; Fatty Acids; Lauric Acids; Drug Resistance, Bacterial; Humans
PubMed: 33046677
DOI: 10.4014/jmb.2008.08027 -
Anti-cancer Agents in Medicinal... 2020microRNAs are known to regulate various protein-coding gene expression posttranscriptionally. Fatty acids are cell membrane constituents and are also known to influence...
BACKGROUND
microRNAs are known to regulate various protein-coding gene expression posttranscriptionally. Fatty acids are cell membrane constituents and are also known to influence the biological activities of the cells like signal transduction, growth and differentiation of the cells, apoptosis induction, and other physiological functions. In our experiments, we used lauric acid to analyse its effects on human cancerous cell lines.
OBJECTIVE
Our objective was to speculate the miRNA expression profile in lauric acid treated and untreated cancerous cell lines and further study the metabolic pathways of the targeted tumour suppressor and oncogenes.
METHODS
The KB cells and HepG2 cells were treated with lauric acid and miRNA was isolated and the expression of tumour suppressor and oncogenic miRNA was measured by quantitative PCR. The untreated cells were used as control. The metabolic pathways of the target tumour suppressor and oncogenes were examined by GeneMANIA software.
RESULTS
Interestingly, the lauric acid treatment suppresses the expression of oncogenic miRNA and significantly upregulated the expression of some tumour suppressor miRNAs. GeneMANIA metabolic pathway revealed that the upregulated tumour suppressor miRNAs regulate several cancer-associated pathways such as DNA damage, signal transduction p53 class mediator, stem cell differentiation, cell growth, cell cycle phase transition, apoptotic signalling pathway, cellular response to stress and radiation, etc. whereas oncogenic miRNAs regulate the cancer-associated pathway like cell cycle phase transition, apoptotic signalling pathway, cell growth, response to oxidative stress, immune response activating cell surface protein signalling pathway, cyclin-dependent protein kinase activity, epidermal growth factor receptor signalling pathways, etc. Conclusion: In our study, we found that lauric acid works as an anticancer agent by altering the expression of miRNAs.
Topics: Antineoplastic Agents; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Hep G2 Cells; Humans; KB Cells; Lauric Acids; MicroRNAs; Structure-Activity Relationship
PubMed: 32156243
DOI: 10.2174/1871520620666200310091719 -
International Journal of Molecular... Apr 2023Although gemcitabine (GEM) is widely used in chemotherapy for pancreatic ductal adenocarcinoma (PDA), drug resistance restricts its clinical effectiveness. To examine...
Although gemcitabine (GEM) is widely used in chemotherapy for pancreatic ductal adenocarcinoma (PDA), drug resistance restricts its clinical effectiveness. To examine the mechanism of GEM resistance, we established two GEM-resistant cell lines from human PDA cells by continuous treatment with GEM and CoCl-induced chemical hypoxia. One resistant cell line possessed reduced energy production and decreased mitochondrial reactive oxygen species levels, while the other resistant cell line possessed increased stemness. In both cell lines, ethidium bromide-stained mitochondrial DNA levels decreased, suggesting mitochondrial DNA damage. Inhibition of hypoxia-inducible factor-1α in both cell lines did not restore the GEM sensitivity. In contrast, treatment of both cell types with lauric acid (LAA), a medium-chain fatty acid, restored GEM sensitivity. These results suggest that decreased energy production, decreased mitochondrial reactive oxygen species levels, and increased stemness associated with mitochondrial damage caused by GEM lead to GEM resistance, and that hypoxia may promote this process. Furthermore, forced activation of oxidative phosphorylation by LAA could be a tool to overcome GEM resistance. Clinical verification of the effectiveness of LAA in GEM resistance is necessary in the future.
Topics: Humans; Gemcitabine; Deoxycytidine; Drug Resistance, Neoplasm; Reactive Oxygen Species; Cell Line, Tumor; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; DNA, Mitochondrial; Apoptosis
PubMed: 37108667
DOI: 10.3390/ijms24087506 -
European Journal of Pharmacology Oct 2023During ischemic stroke, higher glucose level linked worse outcomes were reported even in patients without pre-existing diabetes. Evidence suggest that such worse stroke...
During ischemic stroke, higher glucose level linked worse outcomes were reported even in patients without pre-existing diabetes. Evidence suggest that such worse stroke outcomes were mainly due to production of reactive, toxic glucose metabolites that expands oxidative damage inside the brain. As a consequence of high oxidative stress, microvasculature structures and tight junctions compromised their functionally, infarct volume expands and brain edema exacerbates. In a mouse model of ischemic stroke with induced acute hyperglycaemia, Lauric acid (LA) as a natural saturated fatty acid demonstrated neuroprotection by attenuating infarct volume and brain edema. In addition, in the ipsilateral hyperglycaemic brain, the LA significantly increased the expression of tight junction representative protein (occludin) as well as anti-oxidative markers; Manganese superoxide dismutase (Mn) SOD, Extracellular superoxide dismutase (Ec-SOD) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) in the ipsilateral region against hyperglycemic ischemic stroke. LA treated animals showed a significant reduction in the production of lipid peroxidation products (4-HNE) in the microvascular structures, maintained the blood brain barrier (BBB) integrity. LA linked neuroprotective outcomes were further confirmed by behavioral tests, where functional outcomes and motor coordination were improved significantly. Furthermore, LA treatment enhanced food intake, decreased mortality rate, and net body weight loss. Conclusively, LA modulated ischemic insult exacerbated by hyperglycemia and provided neuroprotection.
Topics: Mice; Animals; Neuroprotection; Brain Edema; Hyperglycemia; Neuroprotective Agents; Stroke; Oxidative Stress; Brain Ischemia; Disease Models, Animal; Superoxide Dismutase; Superoxide Dismutase-1; Glucose; Ischemic Stroke; Infarction
PubMed: 37572940
DOI: 10.1016/j.ejphar.2023.175990 -
Acta Tropica May 2022Iron oxide nanoparticles (IONPs) have been indicated for the control of parasites and intermediate hosts, as well as applications in several sectors of nanomedicine....
Iron oxide nanoparticles (IONPs) have been indicated for the control of parasites and intermediate hosts, as well as applications in several sectors of nanomedicine. However, knowledge regarding its toxicity, mechanisms of action and the role of functionalization in gastropods that act as intermediate hosts of neglected disease parasites is still scarce. The present study aimed to evaluate the toxicity of lauric acid bilayer-functionalized IONPs (LA-IONPs), lauric acid isolated (LA) and iron ions in embryos and newly-hatched Biomphalaria glabrata. The snails were exposed to different concentrations of IONPs, LA and iron ions (1.0-97.65 mg L) during 144 h (embryos) and 96 h (newly-hatched) and multiple parameters were analyzed, such as mortality, hatching rate, developmental delay, and morphological changes. The results showed that both iron forms (LA-IONPs and iron ions) and LA promoted mortality, hatching inhibition and morphological changes in snail embryos in a concentration-dependent patterns. Embryos also showed iron bioaccumulation after exposure to both iron forms. High toxicity was observed in newly-hatched snails compared to embryos, indicating the protective role of ovigerous masses during the early developmental stages. LA induced high developmental toxicity compared to LA-IONPs and iron ions. Results showed the molluscicide activity of LA-IONPs and isolated LA, indicating their potential use as molluscicide in the snail control program.
Topics: Animals; Biomphalaria; Fresh Water; Lauric Acids; Magnetic Iron Oxide Nanoparticles; Snails
PubMed: 35150640
DOI: 10.1016/j.actatropica.2022.106362 -
Carbohydrate Polymers Sep 2022Hydrophobic-modified starch complexes have the potential to form Pickering emulsions and improve the oxidative stability of flaxseed oil. Here, V-type starch-lauric acid...
Hydrophobic-modified starch complexes have the potential to form Pickering emulsions and improve the oxidative stability of flaxseed oil. Here, V-type starch-lauric acid complexes (SLACs) were fabricated via solid encapsulation within 0.5-12 h and applied in flaxseed oil Pickering emulsions. Complexing index, X-ray diffraction and differential scanning calorimetry analyses confirmed that the degree of complexation increased with the reaction time. Pickering emulsion gels stabilised by SLACs generated with reaction times of 6 h and 12 h exhibited good storage stability and high yield stress, G' values and apparent viscosity. Confocal laser scanning microscopy and cryo-scanning electron microscopy revealed a gelation mechanism involving increased interface roughness and enhanced droplet-droplet interaction. In comparison to pure flaxseed oil, higher thermo-oxidative resistance was observed at 130 °C, with a markedly longer oxidation induction for emulsions and emulsion gels stabilised by SLACs. Our findings could assist in the design of hydrophobic-modified starch and provide a new paradigm for delaying oil oxidation.
Topics: Emulsions; Gels; Lauric Acids; Linseed Oil; Oxidative Stress; Particle Size; Starch; Water
PubMed: 35725189
DOI: 10.1016/j.carbpol.2022.119715