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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 -
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 -
Nutrients Apr 2024The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against...
The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.
Topics: Animals; Interleukin-33; Atherosclerosis; Male; Mice; Fatty Acids; Mice, Knockout; Humans; Disease Models, Animal; Palmitic Acid; Apolipoproteins E; Diet, High-Fat; Interleukin-1 Receptor-Like 1 Protein; Endothelial Cells; Mice, Knockout, ApoE; Lymphocytes; Mice, Inbred C57BL; Aorta; Immunity, Innate
PubMed: 38674885
DOI: 10.3390/nu16081195 -
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 -
BMC Cancer Jan 2024Obesity-induced abnormal bone marrow microenvironment is one of the important risk element for bone metastasis in prostate cancer (PCa). The present study aimed to...
BACKGROUND
Obesity-induced abnormal bone marrow microenvironment is one of the important risk element for bone metastasis in prostate cancer (PCa). The present study aimed to determine whether obesity-induced elevation in palmitic acid (PA), which is the most abundant of the free fatty acids (FFAs), increased CCL2 via the GPRs/KLF7 pathway in bone marrow adipocytes (BMA) to facilitate PCa growth and metastasis.
METHODS
We constructed a bone-tumor bearing mouse model with obesity through high-fat diet, and observed the tumor formation ability of PCa cells. In vitro, observe the effect of PA on the expression level of CCL2 in BMA through GPRs/KLF7 signaling pathway. After co-culture of BMA and PCa cells, CCK8 assay and transwell experiment were used to detect the changes in biological behavior of PCa cells stimulated by BMA.
RESULTS
The BMA distribution in the bone marrow cavity of BALB/c nude mice fed with the high-fat diet (HFD) was evidently higher than that in the mice fed with the normal diet (ND). Moreover, HFD-induced obesity promoted KLF7/CCL2 expression in BMA and PCa cell growth in the bone marrow cavity of the mice. In the vitro experiment, a conditioned medium with increased CCL2 obtained from the BMA cultured with PA (CM-BMA-PA) was used for culturing the PCa cell lines, which evidently enhanced the proliferation, invasion, and migration ability. KLF7 significantly increased the CCL2 expression and secretion levels in BMA by targeting the promoter region of the CCL2 gene. In addition, GPR40/120 engaged in the PA-induced high KLF7/CCL2 levels in BMA to facilitate the malignant progression of PC-3 cells.
CONCLUSIONS
PA-activated GPRs/KLF7/CCL2 pathway in BMA facilitates prostate cancer growth and metastasis.
Topics: Animals; Humans; Male; Mice; Adipocytes; Bone Marrow; Bone Neoplasms; Cell Line, Tumor; Chemokine CCL2; Kruppel-Like Transcription Factors; Mice, Nude; Obesity; Palmitic Acid; Prostatic Neoplasms; Tumor Microenvironment
PubMed: 38221626
DOI: 10.1186/s12885-024-11826-5 -
Cell Stress & Chaperones Mar 2021Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of...
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of GA on inflammatory response of ARPE-19 cells remains unclear. In our study, ARPE-19 cells were stimulated by palmitic acid (PA) induction in the presence of 30 mM glucose and then treated with 0.5, 1, 2, 5, 10, or 20 μM GA. CCK-8 assay showed that cell viability was increased by GA treatment at doses of 0.5, 1, and 2 μM instead of higher doses. ELISA analysis found that GA dose-dependently reduced the production of pro-inflammatory mediators TNF-α and IL-1β. Western blot indicated that GA downregulated the expression of NLRP3 inflammasome components including TXNIP, NLRP3, ASC, cleaved-caspase-1, and cleaved-IL-1β in a dose-dependent manner. In addition, Western blot and immunofluorescence analysis suggested that GA effectively increased the protein level of nuclear factor E2-related factor-2 (Nrf2). RT-qPCR showed that GA significantly increased the mRNA levels of Heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase1 (NQO1). Furthermore, Nrf2 siRNA transfection confirmed the above effects of GA. In total, subtoxic doses of GA significantly flattened the inflammatory response induced by HG and PA in ARPE-19 cells via modulating the Nrf2 signaling pathway.
Topics: Cell Line; Diabetic Retinopathy; Humans; Inflammation; NF-E2-Related Factor 2; Palmitic Acid; Xanthones
PubMed: 33245515
DOI: 10.1007/s12192-020-01182-1 -
BioMed Research International 2022Cells were divided into 5 groups-control, high-fat, 10 nmol/L LR + 0.6 mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6 mmol/L PA (100LR), and 1000 nmol/L... (Review)
Review
METHODS
Cells were divided into 5 groups-control, high-fat, 10 nmol/L LR + 0.6 mmol/L palmitic acid (PA) (10LR), 100 nmol/L LR + 0.6 mmol/L PA (100LR), and 1000 nmol/L LR + 0.6 mmol/L PA (1000LR). CCK-8 method to detect cell viability, GPO-PAP enzymatic method to detect intracellular triglyceride content, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting methods to detect fatty acid translocase CD36 (FAT/CD36) and fatty acid binding protein 4 (FABP4) in L6 cells, glucose-regulated protein 78 (GRP78), glucose transporter 4 (GLUT4) expression at the mRNA and protein levels, respectively, were performed.
RESULTS
We found that after PA intervention for 24 h, the cell viability decreased significantly; the cell viability of the LR group was higher than that of the high-fat group ( < 0.01). After PA intervention, compared with those in the high-fat group, GRP-78, FAT/CD36, FABP4 mRNA ((4.36 ± 0.32 vs. 8.15 ± 0.35); (1.00 ± 0.04 vs. 2.46 ± 0.08); (2.88 ± 0.55 vs. 8.29 ± 0.52), < 0.01) and protein ((3338.13 ± 333.15 vs. 4963.98 ± 277.29); (1978.85 ± 124.24 vs. 2676.07 ± 100.64); (3372.00 ± 219.84 vs. 6083.20 ± 284.70), both < 0.01) expression decreased in the LR group. The expression levels of GLUT4 mRNA ((0.75 ± 0.04 vs. 0.34 ± 0.03), < 0.01) and protein ((3443.71 ± 191.89 vs. 2137.79 ± 118.75), < 0.01) increased.
CONCLUSION
Therefore, we conclude that LR can reverse PA-induced cell inactivation and lipid deposition, which may be related to the change in GRP-78, FAT/CD36, FABP4, GLUT4, and other factors.
Topics: Palmitic Acid; Glucagon-Like Peptide-1 Receptor; Proteins; CD36 Antigens; RNA, Messenger; Myoblasts
PubMed: 36619308
DOI: 10.1155/2022/6237405 -
International Journal of Molecular... May 2021The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic...
The excessive accumulation of lipids in hepatocytes induces a type of cytotoxicity called hepatic lipotoxicity, which is a fundamental contributor to liver metabolic diseases (such as NAFLD). Magnesium isoglycyrrhizinate (MGIG), a magnesium salt of the stereoisomer of natural glycyrrhizic acid, is widely used as a safe and effective liver protectant. However, the mechanism by which MGIG protects against NAFLD remains unknown. Based on the significant correlation between NAFLD and the reprogramming of liver metabolism, we aimed to explore the beneficial effects of MGIG from a metabolic viewpoint in this paper. We treated HepaRG cells with palmitic acid (PA, a saturated fatty acid of C16:0) to induce lipotoxicity and then evaluated the antagonistic effect of MGIG on lipotoxicity by investigating the cell survival rate, DNA proliferation rate, organelle damage, and endoplasmic reticulum stress (ERS). Metabolomics, lipidomics, and isotope tracing were used to investigate changes in the metabolite profile, lipid profile, and lipid flux in HepaRG cells under different intervention conditions. The results showed that MGIG can indeed protect hepatocytes against PA-induced cytotoxicity and ERS. In response to the metabolic abnormality of lipotoxicity, MGIG curtailed the metabolic activation of lipids induced by PA. The content of total lipids and saturated lipids containing C16:0 chains increased significantly after PA stimulation and then decreased significantly or even returned to normal levels after MGIG intervention. Lipidomic data show that glycerides and glycerophospholipids were the two most affected lipids. For excessive lipid accumulation in hepatocytes, MGIG can downregulate the expression of the metabolic enzymes (GPATs and DAGTs) involved in triglyceride biosynthesis. In conclusion, MGIG has a positive regulatory effect on the metabolic disorders that occur in hepatocytes under lipotoxicity, and the main mechanisms of this effect are in lipid metabolism, including reducing the total lipid content, reducing lipid saturation, inhibiting glyceride and glycerophospholipid metabolism, and downregulating the expression of metabolic enzymes in lipid synthesis.
Topics: Cell Line, Tumor; Cell Survival; Diacylglycerol O-Acyltransferase; Endoplasmic Reticulum Stress; Gene Expression Regulation; Glycerides; Glycerol-3-Phosphate O-Acyltransferase; Glycerophospholipids; Hepatocytes; Humans; Lipid Metabolism; Lipidomics; Metabolome; Palmitic Acid; Protective Agents; Saponins; Triterpenes
PubMed: 34070938
DOI: 10.3390/ijms22115884 -
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 -
Molecules (Basel, Switzerland) Sep 2022Lam (syn. .) leaves are globally acclaimed for their nutritional content and mitigation of malnutrition. In most impoverished rural communities including Limpopo,...
Lam (syn. .) leaves are globally acclaimed for their nutritional content and mitigation of malnutrition. In most impoverished rural communities including Limpopo, Mpumalanga and KwaZulu Natal of South Africa, powdered leaves of are applied as a nutritional supplement for readily available food such as porridge for malnourished children and even breast-feeding mothers. Widely practiced and admired is also the use of the plant seed in the do-it-yourself purification of water by rural South Africans. This study aimed at identifying the chemical and nutritional marker compounds present in South African seed oils using high resolution 1-2-dimension gas chromatography in order to give scientific validation to its uses in cosmetics and particularly in culinary practices. Results obtained from two-dimension tandem mass spectrometry chemical signature revealed over 250 compounds, five times more than those reported from one-dimension gas chromatography. Whereas previous reports from gas chromatography-mass spectrometry analysis reported oleic acid (70-78%) as the major compound from oil samples from other countries, seed oil from South Africa is marked by 13-octadeaconic acid with 78.62% and 41.9% as the predominant monounsaturated fatty acid in the hexane and dichloromethane extracts respectively. This was followed by vaccenic acid, an isomer of oleic acid at 51% in the acetone extract, 9-octadecanoic acid-(z)-methyl ester at 39.18%, 21.34% and 10.06% in dichloromethane, hexane and acetone extracts respectively. However, a principal component analysis with R = 0.98 of the two-dimension tandem mass spectrometry cum chemometric analysis indicated n-hexadecanoic acid, oleic acid, 9-octadecanoic acid-(z)-methyl ester and -vaccenic acid with a probability of 0.96, 0.88, 0.80 and 0.79 respectively as the marker compounds that should be used for the quality control of seed oils from South Africa. This study demonstrates that South African oils contain C-18 monounsaturated fatty acids similar to oils from Egypt (76.2%), Thailand (71.6%) and Pakistan (78.5%) just to mention but a few. These fatty acids are sunflower and olive oil type-compounds and therefore place seed oil for consideration as a cooking oil amongst its other uses.
Topics: Acetone; Child; Esters; Fatty Acids; Gas Chromatography-Mass Spectrometry; Hexanes; Humans; Methylene Chloride; Moringa; Moringa oleifera; Oleic Acid; Olive Oil; Palmitic Acid; Plant Extracts; Plant Oils; Seeds; South Africa; Stearic Acids; Water
PubMed: 36144484
DOI: 10.3390/molecules27185749