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Galen Medical Journal 2023Overweight and obesity are the most critical risk factors for chronic diseases. The quality of dietary fatty acids as one of the factors affecting fat accumulation has...
BACKGROUND
Overweight and obesity are the most critical risk factors for chronic diseases. The quality of dietary fatty acids as one of the factors affecting fat accumulation has received little attention. This study investigates the association between dietary linoleic acid (LA) and alpha-linolenic acid (ALA) with body fat indices in a sample of healthy Iranian adults.
MATERIALS AND METHODS
In this cohort-based cross-sectional study, 3,195 individuals aged 20 to 60 who participated in the Shiraz University of Medical Science Employees Health Cohort study were included. Dietary intake was assessed using a validated 118-item Food Frequency Questionnaire (FFQ), and body composition was assessed by the bioelectrical impedance analysis method. Multiple linear regression adjusted for relevant confounders was used to determine the associations.
RESULTS
Mean dietary intake of LA was 14.20 ± 7.01 mg/day for men and 13.90 ± 6.71 mg/day for women. Additionally, the daily intake of ALA was 0.18 ± 0.18 mg/day in men and 0.17 ± 0.19 mg/day in women. Dietary intake of ALA for men had an inversely significant association with body fat mass (BFM) (β: -0.585, 95% CI: -1.137, -0.032, P=0.038), percentage of body fat (PBF) (β: -0.537, 95% CI: -0.945, -0.129, P=0.010), Visceral Fat Area (VFA) (β: -2.998, 95% CI: -5.695, -0.302, P=0.029), and Waist to Hip Ratio (WHR) (β: -0.689, 95% CI: -1.339, -0.040, P=0.038).
CONCLUSION
Higher dietary ALA intake was associated with lower BFM, BFP, VAF, and WHR in men. The present study confirms that ALA intake should be considered a preventive treatment to improve body composition. However, further research is recommended in this regard.
PubMed: 38774859
DOI: 10.31661/gmj.v12i.3023 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia,... (Meta-Analysis)
Meta-Analysis Review
Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.
Topics: Adult; Humans; Cardiovascular Diseases; alpha-Linolenic Acid; Overweight; Randomized Controlled Trials as Topic; Cholesterol, HDL; Obesity; Dietary Supplements
PubMed: 37778442
DOI: 10.1016/j.advnut.2023.09.010 -
Viruses Jun 2023Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to...
Emergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need. Since gut fermentation of fiber produces short-chain fatty acids (SCFA) with antiviral potential, developing a fatty acid-based broad-spectrum antiviral was investigated. Molecular docking of fatty acids showed α-linolenic acid (ALA) is likely to interact with CoV-2-S, NL63-CoV-S, and RSV-F, and an ALA-containing liposome interacted with CoV-2 directly, degrading the particle. Furthermore, a combination of ALA and a SCFA-acetate synergistically inhibited CoV2-N expression and significantly reduced viral plaque formation and IL-6 and IL-1β transcript expression in Calu-3 cells, while increasing the expression of IFN-β. A similar effect was also observed in RSV-infected A549 cells. Moreover, mice infected with a murine-adapted SARS-CoV-2 (MA10) and treated with an ALA-liposome encapsulating acetate showed significant reductions in plaque-forming units present in lung tissue and in infection-associated lung inflammation and cytokines. Taken together, these results demonstrate that the ALA liposome-encapsulating acetate can be a promising broad antiviral therapy against respiratory infections.
Topics: Animals; Mice; SARS-CoV-2; Liposomes; alpha-Linolenic Acid; Molecular Docking Simulation; COVID-19; Respiratory Syncytial Virus Infections; Antiviral Agents; Respiratory Syncytial Virus, Human; Acetates
PubMed: 37515117
DOI: 10.3390/v15071429 -
International Journal of Nanomedicine 2021Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility....
PURPOSE
Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.
METHODS
We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.
RESULTS
The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.
CONCLUSION
ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.
Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Endocytosis; Mice; Nanoparticles; Paclitaxel; alpha-Linolenic Acid
PubMed: 34737564
DOI: 10.2147/IJN.S331578 -
Experimental Biology and Medicine... Apr 2023Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy,...
Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy, stroke, spinal cord injury, traumatic brain injury, schizophrenia, and autism spectrum disorders. Underlying mechanisms are diverse, but a functional impairment and loss of GABAergic inhibitory neurons are common features in many of these disorders. While novel therapies abound to correct for the loss of GABAergic inhibitory neurons, it has been difficult at best to improve the activities of daily living for the majority of patients. Alpha-linolenic acid (ALA) is an essential omega-3 polyunsaturated fatty acid found in plants. ALA exerts pleiotropic effects in the brain that attenuate injury in chronic and acute brain disease models. However, the effect of ALA on GABAergic neurotransmission in hyperexcitable brain regions involved in neuropsychiatric disorders, such as the basolateral amygdala (BLA) and CA1 subfield of the hippocampus, is unknown. Administration of a single dose of ALA (1500 nmol/kg) subcutaneously increased the charge transfer of inhibitory postsynaptic potential currents mediated by GABA receptors in pyramidal neurons by 52% in the BLA and by 92% in the CA1 compared to vehicle animals a day later. Similar results were obtained in pyramidal neurons from the BLA and CA1 when ALA was bath-applied in slices from naïve animals. Importantly, pretreatment with the high-affinity, selective TrkB inhibitor, k252, completely abolished the ALA-induced increase in GABAergic neurotransmission in the BLA and CA1, suggesting a brain-derived neurotrophic factor (BDNF)-mediated mechanism. Addition of mature BDNF (20 ng/mL) significantly increased GABA receptor inhibitory activity in the BLA and CA1 pyramidal neurons similar to the results obtained with ALA. ALA may be an effective treatment for neuropsychiatric disorders where hyperexcitability is a major feature.
Topics: Rats; Humans; Animals; Basolateral Nuclear Complex; alpha-Linolenic Acid; Brain-Derived Neurotrophic Factor; Rats, Sprague-Dawley; Activities of Daily Living; Synaptic Transmission; Receptors, GABA-A
PubMed: 37208920
DOI: 10.1177/15353702231165010 -
Cell Adhesion & Migration Dec 2021Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques...
Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques and Tau seed fabricate the activation of microglia. The seeding effect of extracellular Tau species is an emerging aspect to study about Tauopathies in AD. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. The excessive neuroinflammation cumulatively hampers phagocytic function of microglia reducing the clearance of extracellular protein aggregates. Omega-3 fatty acids, especially docosahexaenoic acid and eicosapentaenoic acid, are recognized to induce anti-inflammatory phenotype of microglia. In addition to increased cytokine production, omega-3 fatty acids enhance phagocytic receptors expression in microglia. In this study, we have observed the phagocytosis of extracellular Tau in the presence of α-linolenic acid (ALA). The increased phagocytosis of extracellular Tau monomer and aggregates have been observed upon ALA exposure to microglia cells. After internalization, the degradation status of Tau has been studied with early and late endosomal markers Rab5 and Rab7. Further, the lysosome-mediated degradation of internalized Tau was studied with LAMP-2A, a lysosome marker. The enhanced migratory ability in the presence of ALA could be beneficial for microglia to access the target and clear it. The increased migration of microglia was found to induce the microtubule-organizing center repolarization. The data indicate that the dietary fatty acids ALA could significantly enhance phagocytosis and intracellular degradation of internalized Tau. Our results suggest that microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids.
Topics: Alzheimer Disease; Humans; Microglia; Neuroinflammatory Diseases; Phagocytosis; alpha-Linolenic Acid; tau Proteins
PubMed: 33724164
DOI: 10.1080/19336918.2021.1898727 -
International Journal of Molecular... Jul 2023Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease... (Review)
Review
Cancer is a significant global public health issue and, despite advancements in detection and treatment, the prognosis remains poor. Cancer is a complex disease characterized by various hallmarks, including dysregulation in apoptotic cell death pathways. Apoptosis is a programmed cell death process that efficiently eliminates damaged cells. Several studies have indicated the involvement of polyunsaturated fatty acids (PUFAs) in apoptosis, including omega-3 PUFAs such as alpha-linolenic acid, docosahexaenoic acid, and eicosapentaenoic acid. However, the role of omega-6 PUFAs, such as linoleic acid, gamma-linolenic acid, and arachidonic acid, in apoptosis is controversial, with some studies supporting their activation of apoptosis and others suggesting inhibition. These PUFAs are essential fatty acids, and Western populations today have a high consumption rate of omega-6 to omega-3 PUFAs. This review focuses on presenting the diverse molecular mechanisms evidence in both in vitro and in vivo models, to help clarify the controversial involvement of omega-3 and omega-6 PUFAs in apoptosis mechanisms in cancer.
Topics: Humans; Fatty Acids, Unsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Docosahexaenoic Acids; Apoptosis; Neoplasms
PubMed: 37511450
DOI: 10.3390/ijms241411691 -
Journal of Animal Science and... Sep 2022Transgenerational effects of certain nutrients such as essential fatty acids are gaining increased attention in the field of human medicine and animal sciences as a new... (Review)
Review
Transgenerational effects of certain nutrients such as essential fatty acids are gaining increased attention in the field of human medicine and animal sciences as a new tool to improve health and animal performance during perinatal life. Omega-3 (n-3) and omega-6 (n-6) fatty acids are denoted by the position of the first double bond from methyl end of the hydrocarbon chain. Alpha-linolenic acid (18:3 n-3) and linoleic acid (18:2 n-6) are essential n-3 and n-6 fatty acids and cannot be synthesized by the vertebrates including chickens. Alpha-linolenic acid and linoleic acid are the parent fatty acids of long chain (> 20-22C) n-3 and n-6 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (20:5 n-3, EPA), docosapentaenoic acid (22:5 n-3/or 22:5 n-6, DPA), docosahexaenoic acid (22:6 n-3, DHA) and arachidonic acid (20:4 n-6). As components of cell membrane phospholipids, PUFA serves as precursors of eicosanoids, act as ligands for membrane receptors and transcription factors that regulate gene expression and are pivotal for normal chick growth and development. Considering the role of egg lipids as the sole source of essential fatty acids to the hatchling, dietary deficiencies or inadequate in ovo supply may have repercussions in tissue PUFA incorporation, lipid metabolism, chick growth and development during pre and early post-hatch period. This review focus on studies showing how maternal dietary n-3 or n-6 fatty acids can lead to remodeling of long chain n-3 and n-6 PUFA in the hatching egg and progeny chick tissue phospholipid molecular species and its impact on chick growth and PUFA metabolism during early life.
PubMed: 36117183
DOI: 10.1186/s40104-022-00757-5 -
Metabolites Sep 2023Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting....
Epidemiological evidence regarding the effect of omega-3 polyunsaturated fatty acid (PUFA) supplementation on inflammatory bowel disease (IBD) is conflicting. Additionally, little evidence exists regarding the effects of specific omega-3 components on IBD risk. We applied two-sample Mendelian randomization (MR) to disentangle the effects of omega-3 PUFAs (including total omega-3, α-linolenic acid, eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA)) on the risk of IBD, Crohn's disease (CD) and ulcerative colitis (UC). Our findings indicated that genetically predicted increased EPA concentrations were associated with decreased risk of IBD (odds ratio 0.78 (95% CI 0.63-0.98)). This effect was found to be mediated through lower levels of linoleic acid and histidine metabolites. However, we found limited evidence to support the effects of total omega-3, α-linolenic acid, and DHA on the risks of IBD. In the () region, robust colocalization evidence was observed, suggesting the primary role of the gene in mediating the effects of omega-3 PUFAs on IBD. Therefore, the present MR study highlights EPA as the predominant active component of omega-3 fatty acids in relation to decreased risk of IBD, potentially via its interaction with linoleic acid and histidine metabolites. Additionally, the gene likely mediates the effects of omega-3 PUFAs on IBD risk.
PubMed: 37887366
DOI: 10.3390/metabo13101041 -
BMC Microbiology Nov 2023Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation...
BACKGROUND
Infantile cholestasis (IC) is the most common hepatobiliary disease in infants, resulting in elevated direct bilirubin levels. Indeed, hepatointestinal circulation impacts bile acid and bilirubin metabolism. This study evaluates changes in the gut microbiota composition in children with IC and identifies abnormal metabolite profiles associated with microbial alterations.
RESULTS
The gut microbiota in the IC group exhibits the higher abundance of Veillonella, Streptococcus and Clostridium spp. (P < 0.05), compared to healthy infants (CON) group. Moreover, the abundance of Ruminococcus, Vibrio butyricum, Eubacterium coprostanogenes group, Intestinibacter, and Faecalibacterium were lower (P < 0.05). In terms of microbiota-derived metabolites, the levels of fatty acids (palmitoleic, α-linolenic, arachidonic, and linoleic) (P < 0.05) increased and the levels of amino acids decreased in IC group. Furthermore, the abundances of Ruminococcus, Eubacterium coprostanoligenes group, Intestinibacter and Butyrivibrio are positively correlated with proline, asparagine and aspartic acid, but negatively correlated with the α-linolenic acid, linoleic acid, palmitoleic acid and arachidonic acid. For analysis of the relationship between the microbiota and clinical index, it was found that the abundance of Veillonella and Streptococcus was positively correlated with serum bile acid content (P < 0.05), while APTT, PT and INR were negatively correlated with Faecalibalum and Ruminococcus (P < 0.05).
CONCLUSION
Microbiota dysbiosis happened in IC children, which also can lead to the abnormal metabolism, thus obstructing the absorption of enteral nutrition and aggravating liver cell damage. Veillonella, Ruminococcus and Butyrivibrio may be important microbiome related with IC and need further research.
Topics: Infant; Child; Humans; Gastrointestinal Microbiome; Cholestasis; Liver; Streptococcus; Bilirubin; Bile Acids and Salts
PubMed: 37980506
DOI: 10.1186/s12866-023-03115-1