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International Journal of Molecular... Jun 2023One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common...
One of the largest health problems worldwide is the development of chronic noncommunicable diseases due to the consumption of hypercaloric diets. Among the most common alterations are cardiovascular diseases, and a high correlation between overnutrition and neurodegenerative diseases has also been found. The urgency in the study of specific damage to tissues such as the brain and intestine led us to use to study the metabolic effects caused by the consumption of fructose and palmitic acid in specific tissues. Thus, third instar larvae (96 ± 4 h) of the wild Canton-S strain of were used to perform transcriptomic profiling in brain and midgut tissues to test for the potential metabolic effects of a diet supplemented with fructose and palmitic acid. Our data infer that this diet can alter the biosynthesis of proteins at the mRNA level that participate in the synthesis of amino acids, as well as fundamental enzymes for the dopaminergic and GABAergic systems in the midgut and brain. These also demonstrated alterations in the tissues of flies that may help explain the development of various reported human diseases associated with the consumption of fructose and palmitic acid in humans. These studies will not only help to better understand the mechanisms by which the consumption of these alimentary products is related to the development of neuronal diseases but may also contribute to the prevention of these conditions.
Topics: Animals; Humans; Drosophila melanogaster; Fructose; Palmitic Acid; Larva; Neurodegenerative Diseases; Gene Expression
PubMed: 37373426
DOI: 10.3390/ijms241210279 -
Drug Metabolism and Personalized Therapy Mar 2021In a previous investigation we searched for the occurrence of palmitic acid ester compounds of delta9-tetrahydrocannabinol (THC) and its primary metabolite...
OBJECTIVES
In a previous investigation we searched for the occurrence of palmitic acid ester compounds of delta9-tetrahydrocannabinol (THC) and its primary metabolite 11-hydroxy-delta9-THC (11-OH-THC) in human body fluids and tissues (THC palmitic acid monoester [THC-Pal] and 11-OH-THC palmitic acid diester [11-OH-THC-DiPal]). As those esters could not be detected in various human body fluids (e.g. blood) or tissues (e.g. adipose tissue) we extended the investigation analyzing adipose tissue samples of mice previously given synthetic THC or a cannabis extract.
METHODS
In total, 48 adipose tissue samples previously tested positive for THC by means of a liquid chromatographic triple quadrupole mass spectrometric (LC-QQQ-MS) method were analyzed for the presence of THC-Pal and 11-OH-THC-DiPal by means of LC-QQQ-MS.
RESULTS
THC-Pal and 11-OH-THC-DiPal were not detected among the adipose tissue samples analyzed despite the presence of high THC concentrations within the adipose tissue. THC concentrations in adipose tissue were in a range of approximately 7-2,595 ng/g (median: 468 ng/g, average: 704 ng/g).
CONCLUSIONS
A (site-specific) synthesis of 11-OH-THC palmitic acid monoesters (11-hydroxy-delta9-THC-1-palmitate and 11-palmitoyloxy-delta9-THC) still remains to be done. After synthesis of these monoesters, their presence in the body fluids and tissues after THC administration should be investigated.
Topics: Animals; Chromatography, Liquid; Dronabinol; Esters; Gas Chromatography-Mass Spectrometry; Humans; Mice; Palmitic Acid
PubMed: 34412174
DOI: 10.1515/dmpt-2020-0151 -
International Journal of Molecular... Mar 2021Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of sarcopenic obesity. Herein, we chose two non-cytotoxic...
Palmitic acid (PA), a saturated fatty acid enriched in high-fat diet, has been implicated in the development of sarcopenic obesity. Herein, we chose two non-cytotoxic concentrations to better understand how excess PA could impact myotube formation or diameter without inducing cell death. Forty-eight hours of 100 µM PA induced a reduction of myotube diameter and increased the number of type I fibers, which was associated with increased miR-206 expression. Next, C2C12 myotube growth in the presence of PA was evaluated. Compared to control cells, 150 µM PA reduces myoblast proliferation and the expression of and miR-206 and miR-133a expression, leading to a reduced number and diameter of myotubes. PA (100 µM), despite not affecting proliferation, impairs myotube formation by reducing the expression of Myf5 and miR-206 and decreasing protein synthesis. Interestingly, 100 and 150 µM PA-treated myotubes had a higher number of type II fibers than control cells. In conclusion, PA affects negatively myotube diameter, fusion, and metabolism, which may be related to myomiRs. By providing new insights into the mechanisms by which PA affects negatively skeletal muscle, our data may help in the discovery of new targets to treat sarcopenic obesity.
Topics: Animals; Cell Line; Gene Expression Regulation; Mice; MicroRNAs; Muscle Development; Myoblasts, Skeletal; Palmitic Acid
PubMed: 33803124
DOI: 10.3390/ijms22052748 -
The Science of the Total Environment May 2021The toxicity of arsenic (As) can be influenced by many nutrients in food. However, the combined effects and underlying mechanisms of As and palmitic acid (PA) are still...
The toxicity of arsenic (As) can be influenced by many nutrients in food. However, the combined effects and underlying mechanisms of As and palmitic acid (PA) are still unclear. Here, cell viability, oxidative stress, lipids accumulation, gene expression profiles, and metabolome profiles of human hepatoma HepG2 cells exposed to As, PA, and As + PA were analyzed and compared. Results showed that co-exposure of 100 μM PA and 2 μM As induced lower cell viability, higher intracellular reactive oxygen species level, more lipid droplet accumulation, and more intracellular triglyceride contents than As alone or PA alone exposure. High-throughput quantitative PCR and H NMR-based metabolomics analysis showed that co-exposure of As and PA caused all toxic effects on gene expression and metabolome profiles induced by As alone or PA alone exposure, and showed higher toxicities. Gene expression profiles in the As + PA group had higher similarity with those in the As group than the PA group. However, PA played a more important role in metabolism disorder than As in their interactive effects. Oxidative stress and lipid metabolism disorder were found to be the main toxic effects in the As + PA group. Several differentially expressed genes (such as OXR1, OXSR1, INSR, and PPARA) and changed metabolites (such as pyruvate, acetate, and L-phenylalanine) were involved in the combined toxicity of As and PA. This study provides basic information on the interactive effects of As and PA, which is useful for the health risk assessment of As and FFA.
Topics: Arsenic; Carcinoma, Hepatocellular; Hep G2 Cells; Humans; Lipid Metabolism; Lipid Metabolism Disorders; Oxidative Stress; Palmitic Acid
PubMed: 33736254
DOI: 10.1016/j.scitotenv.2020.144849 -
Journal of Dairy Science Feb 2024The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent...
The concept that fat supplementation impairs total-tract fiber digestibility in ruminants has been widely accepted over the past decades. Nevertheless, the recent interest in the dietary fatty acid profile to dairy cows enlightened the possible beneficial effect of specific fatty acids (e.g., palmitic, stearic, and oleic acids) on total-tract fiber digestibility. Because palmitic, stearic, and oleic acids are the main fatty acids present in ruminal bacterial cells, we hypothesize that the dietary supply of these fatty acids will favor their incorporation into the bacterial cell membranes, which will support the growth and enrichment of fiber-digesting bacteria in the rumen. Our objective in this experiment was to investigate how dietary supply of palmitic, stearic, and oleic acid affect fiber digestion, bacterial membrane fatty acid profile, microbial growth, and composition of the rumen bacterial community. Diets were randomly assigned to 8 single-flow continuous culture fermenters arranged in a replicated 4 × 4 Latin square with four 11-d experimental periods. Treatments were (1) a control basal diet without supplemental fatty acids (CON); (2) the control diet plus palmitic acid (PA); (3) the control diet plus stearic acid (SA); and (4) the control diet plus oleic acid (OA). All fatty acid treatments were included in the diet at 1.5% of the diet (dry matter [DM] basis). The basal diet contained 50% orchardgrass hay and 50% concentrate (DM basis) and was supplied at a rate of 60 g of DM/d in 2 equal daily offers (0800 and 1600 h). Data were analyzed using a mixed model considering treatments as fixed effect and period and fermenter as random effects. Our results indicate that PA increased in vitro fiber digestibility by 6 percentage units compared with the CON, while SA had no effect and OA decreased fiber digestibility by 8 percentage units. Oleic acid decreased protein expression of the enzymes acetyl-CoA carboxylase compared with CON and PA, while fatty acid synthase was reduced by PA, SA, and OA. We observed that PA, but not SA or OA, altered the bacterial community composition by enhancing bacterial groups responsible for fiber digestion. Although the dietary fatty acids did not affect the total lipid content and the phospholipid fraction in the bacterial cell, PA increased the flow of anteiso C13:0 and anteiso C15:0 in the phospholipidic membrane compared to the other treatments. In addition, OA increased the flow of C18:1 cis-9 and decreased C18:2 cis-9,cis-12 in the bacterial phospholipidic membranes compared to the other treatments. Palmitic acid tended to increase bacterial growth compared to other treatments, whereas SA and OA did not affect bacterial growth compared with CON. To our knowledge, this is the first research providing evidence that palmitic acid supports ruminal fiber digestion through shifts in bacterial fatty acid metabolism that result in changes in growth and abundance of fiber-degrading bacteria in the microbial community.
Topics: Cattle; Female; Animals; Oleic Acid; Dietary Supplements; Milk; Lactation; Rumen; Digestion; Fatty Acids; Diet; Palmitic Acid
PubMed: 37776997
DOI: 10.3168/jds.2023-23568 -
Nutrients Feb 2020Fats that are rich in palmitic or stearic acids can be interesterified to increase their applicability for the production of certain foods. When compared with palmitic... (Comparative Study)
Comparative Study
Fats that are rich in palmitic or stearic acids can be interesterified to increase their applicability for the production of certain foods. When compared with palmitic acid, stearic acid lowers low-density lipoprotein (LDL)-cholesterol, which is a well-known risk factor for coronary heart disease (CHD), but its effects on other cardiometabolic risk markers have been studied less extensively. In addition, the positional distribution of these two fatty acids within the triacylglycerol molecule may affect their metabolic effects. The objective was to compare the longer-term and postprandial effects of (interesterified) fats that are rich in either palmitic or stearic acids on cardiometabolic risk markers in humans. Two searches in PubMed/Medline, Embase (OVID) and Cochrane Library were performed; one to identify articles that studied effects of the position of palmitic or stearic acids within the triacylglycerol molecule and one to identify articles that compared side-by-side effects of palmitic acid with those of stearic acid. The interesterification of palmitic or stearic acid-rich fats does not seem to affect fasting serum lipids and (apo) lipoproteins. However, substituting palmitic acid with stearic acid lowers LDL-cholesterol concentrations. Postprandial lipemia is attenuated if the solid fat content of a fat blend at body temperature is increased. How (the interesterification of) palmitic or stearic acid-rich fats affects other cardiometabolic risk markers needs further investigation.
Topics: Biomarkers; Cardiovascular Diseases; Esterification; Humans; Metabolic Syndrome; Palmitic Acid; Risk Factors; Stearic Acids
PubMed: 32111040
DOI: 10.3390/nu12030615 -
International Journal of Molecular... Jun 2023Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule...
Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.
Topics: Humans; Aminolevulinic Acid; Palmitic Acid; Apoptosis; Endoplasmic Reticulum Chaperone BiP; Heme Oxygenase-1; Endoplasmic Reticulum Stress
PubMed: 37373300
DOI: 10.3390/ijms241210151 -
International Journal of Molecular... Nov 2022Soybean () is an important oil crop, but the regulatory mechanisms underlying seed oil accumulation remain unclear. We identified a member of the transcription factor...
Soybean () is an important oil crop, but the regulatory mechanisms underlying seed oil accumulation remain unclear. We identified a member of the transcription factor family, , that is involved in regulating soybean oil content and nodulation. Overexpression of in soybean hairy roots increased the expression of genes involved in glycolysis and de novo lipogenesis, the proportion of palmitic acid (16:0), and the number of root nodules. The effect of in increasing the number of root nodules via regulating the proportion of palmitic acid was confirmed in a recombinant inbred line (RIL) population. shows abundant sequence diversity and has likely undergone artificial selection during domestication. An association analysis revealed a correlation between seed oil content and five linked natural variations (Hap1/Hap2) in the promoter region. Natural variations in the promoter were strongly associated with the transcript level, with higher transcript levels in lines carrying than in those carrying . The effects of alleles on seed oil content were confirmed in natural and RIL populations. We identified a favourable allele that can be used to breed new varieties with increased seed oil content and nodulation.
Topics: Glycine max; Palmitic Acid; Plant Proteins; Plant Breeding; Soybean Oil
PubMed: 36430287
DOI: 10.3390/ijms232213793 -
Molecular and Cellular Endocrinology Feb 2023Primary hyperaldosteronism is a major cause of secondary hypertension and carries additional cardiovascular risks beyond that of the elevated blood pressure. Primary...
Primary hyperaldosteronism is a major cause of secondary hypertension and carries additional cardiovascular risks beyond that of the elevated blood pressure. Primary hyperaldosteronism is more prevalent in obese people, and weight loss reduces aldosterone levels. It needs to be determined whether obesity related factors directly contribute to the pathogenesis of primary hyperaldosteronism. Here we show that the non-esterified fatty acids (NEFA) palmitic acid, and to a lesser extent, linoleic acid significantly stimulated aldosterone production and steroid enzyme induction in adrenocortical HAC15 cells of human origin. Palmitic acid, linoleic acid, and to a much lesser extent, oleic acid induced the expression of aldosterone synthase. Induction of the Steroidogenic Acute Regulatory Protein (StAR) was modest. Increased aldosterone secretion was independent of fatty acid beta-oxidation in the mitochondria but may involve free fatty acid receptor 1 (FFAR1/GPR40) and endoplasmic reticulum (ER) stress. Palmitic acid and linoleic acid induced the expression of C/EBP Homologous Protein (CHOP), a marker of ER stress, correlating with their ability to induce aldosterone synthase gene expression. Palmitic acid, but not linoleic acid decreased mitochondrial potentials and induced uncoupling protein 2 (UCP2). Palmitic acid enhanced, while docosahexaenoic acid (DHA) suppressed aldosterone response to angiotensin II (Ang-II). Our study provides evidence that NEFAs modulate aldosterone production, and further suggests that hyperaldosteronism shares similar pathogenesis with other obesity-related disorders such as metabolic syndrome.
Topics: Humans; Aldosterone; Fatty Acids; Cytochrome P-450 CYP11B2; Hyperaldosteronism; Palmitic Acid; Hypertension
PubMed: 36549461
DOI: 10.1016/j.mce.2022.111836 -
Communications Biology May 2024Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder affecting millions of adults worldwide, but a poor understanding of its...
Intervertebral disc degeneration (IDD) is a highly prevalent musculoskeletal disorder affecting millions of adults worldwide, but a poor understanding of its pathogenesis has limited the effectiveness of therapy. In the current study, we integrated untargeted LC/MS metabolomics and magnetic resonance spectroscopy data to investigate metabolic profile alterations during IDD. Combined with validation via a large-cohort analysis, we found excessive lipid droplet accumulation in the nucleus pulposus cells of advanced-stage IDD samples. We also found abnormal palmitic acid (PA) accumulation in IDD nucleus pulposus cells, and PA exposure resulted in lipid droplet accumulation and cell senescence in an endoplasmic reticulum stress-dependent manner. Complementary transcriptome and proteome profiles enabled us to identify solute carrier transporter (SLC) 43A3 involvement in the regulation of the intracellular PA level. SLC43A3 was expressed at low levels and negatively correlated with intracellular lipid content in IDD nucleus pulposus cells. Overexpression of SLC43A3 significantly alleviated PA-induced endoplasmic reticulum stress, lipid droplet accumulation and cell senescence by inhibiting PA uptake. This work provides novel integration analysis-based insight into the metabolic profile alterations in IDD and further reveals new therapeutic targets for IDD treatment.
Topics: Nucleus Pulposus; Endoplasmic Reticulum Stress; Palmitic Acid; Cellular Senescence; Intervertebral Disc Degeneration; Humans; Lipid Droplets; Male; Female; Adult; Middle Aged
PubMed: 38714886
DOI: 10.1038/s42003-024-06248-9