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Frontiers in Immunology 2021Epidermal growth factor (EGF) acts as a paracrine and autocrine mediator of cell proliferation and differentiation in various types of epithelial cells, such as...
Epidermal growth factor (EGF) acts as a paracrine and autocrine mediator of cell proliferation and differentiation in various types of epithelial cells, such as sebocytes, which produce the lipid-rich sebum to moisturize the skin. However, sebum lipids direct contact and by penetrating through the epidermis may have regulatory roles on epidermal and dermal cells as well. As EGF receptor (EGFR) is expressed throughout the proliferating and the lipid-producing layers of sebaceous glands (SGs) in healthy and acne-involved skin, we investigated the effect of EGF on SZ95 sebocytes and how it may alter the changes induced by palmitic acid (PA), a major sebum component with bioactive roles. We found that EGF is not only a potent stimulator of sebocyte proliferation, but also induces the secretion of interleukin (IL)6 and down-regulates the expression of genes involved in steroid and retinoid metabolism. Importantly, when applied in combination with PA, the PA-induced lipid accumulation was decreased and the cells secreted increased IL6 levels. Functional clustering of the differentially regulated genes in SZ95 sebocytes treated with EGF, PA or co-treated with EGF+PA further confirmed that EGF may be a potent inducer of hyperproliferative/inflammatory pathways (IL1 signaling), an effect being more pronounced in the presence of PA. However, while a group of inflammatory genes was up-regulated significantly in EGF+PA co-treated sebocytes, PA treatment in the absence of EGF, regulated genes only related to cell homeostasis. Meta-analysis of the gene expression profiles of whole acne tissue samples and EGF- and EGF+PA -treated SZ95 sebocytes showed that the EGF+PA co-activation of sebocytes may also have implications in disease. Altogether, our results reveal that PA-induced lipid accumulation and inflammation can be modulated by EGF in sebocytes, which also highlights the need for system biological approaches to better understand sebaceous (immuno)biology.
Topics: Cell Line; Epidermal Growth Factor; Epithelial Cells; Humans; Inflammation; Interleukin-6; Palmitic Acid; Sebaceous Glands; Signal Transduction
PubMed: 34025636
DOI: 10.3389/fimmu.2021.600017 -
Bioprocess and Biosystems Engineering Jul 2020In this work, the process performance of three parallel anaerobic digesters was evaluated while treating emulsified long-chain fatty acids (LCFA) (i.e., palmitic,... (Comparative Study)
Comparative Study
In this work, the process performance of three parallel anaerobic digesters was evaluated while treating emulsified long-chain fatty acids (LCFA) (i.e., palmitic, stearic and oleic acid) at two different organic loading rates (OLR) (2 and 4 g L day). The digester treating palmitic acid achieved a biogas yield of 0.42 ± 0.05 L g COD with a digester effluent COD of 2.3 ± 0.4 g L and VFA concentrations below 250 mg L. Stearic acid showed lower biogas yield values (0.34 ± 0.05 L g COD) with low effluent COD (2.5 ± 0.4 g L) and VFA concentrations (< 350 mg L). On the contrary, anaerobic digestion of oleic acid was accompanied with increased effluent COD (4.5 ± 0.7 g L) and VFA concentrations (2.7 ± 1.5 g L). As such, COD removal efficiency remained at 89 ± 1% compared to 95 ± 1% for the digesters treating palmitic and stearic acid. During continuous digester operation, there was a decrease in VFA concentrations (around 1-2 g L), combined with increasing biogas yield values up to 0.51 ± 0.04 L g COD, possibly due to biomass adaptation to oleic acid. Digester foaming was recorded when the accumulated COD was higher than 200, 1200 and 500 mg COD g MLSS for the digester treating palmitic, stearic and oleic acid, respectively. ADM1 simulation allowed for the determination of the maximum specific LCFA consumption rate constant (km) which was equal to 4.8, 1.6 and 8.0 day for palmitic, stearic and oleic acid respectively.
Topics: Anaerobiosis; Biological Oxygen Demand Analysis; Bioreactors; Fatty Acids; Hydrogen-Ion Concentration; Kinetics; Models, Theoretical; Oleic Acid; Palmitic Acid; Stearic Acids; Temperature
PubMed: 32198548
DOI: 10.1007/s00449-020-02328-2 -
Reproduction (Cambridge, England) Dec 2021Exposure of mouse oocytes to saturated fatty acids (FAs) such as palmitic acid (PA) has been shown to increase lipid content and cause an endoplasmic reticulum (ER)...
Exposure of mouse oocytes to saturated fatty acids (FAs) such as palmitic acid (PA) has been shown to increase lipid content and cause an endoplasmic reticulum (ER) stress response and changes in the mitochondrial redox state. PA can also disrupt Ca2+ stores in other cell types. The links between these intracellular changes, or whether they are prevented by mono-unsaturated FAs such as oleic acid (OA), is unclear. Here, we have investigated the effects of FAs on mouse oocytes, that are maturated in vitro, using coherent anti-Stokes Raman scattering and two-photon fluorescence microscopy. When oocytes were matured in the presence of PA, there were changes in the aggregation pattern and size of lipid droplets that were mitigated by co-incubation in OA. Maturation in PA alone also caused a distinctive disruption of the ER structure. This effect was prevented by incubation of OA with PA. In contrast, maturation of mouse oocytes in medium containing PA was not associated with any significant change in the redox state of mitochondria or the Ca2+ content of intracellular stores. These data suggest that a primary effect of saturated FAs such as PA on oocytes is to disrupt the structure of the ER and this is not due to an effect on the mitochondria or Ca2+ stores.
Topics: Animals; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Mice; Oleic Acid; Oocytes; Palmitic Acid
PubMed: 34866595
DOI: 10.1530/REP-21-0332 -
European Review For Medical and... Jan 2022Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus accompanied with hyperglycemia and hyperlipidemia. Both high blood glucose...
OBJECTIVE
Diabetic peripheral neuropathy (DPN) is a common long-term complication of diabetes mellitus accompanied with hyperglycemia and hyperlipidemia. Both high blood glucose and high blood lipids are key pathogenies for DPN. This research aims to investigate whether the combination of glucose (Glu) and palmitic acid (PA) played a synergistic role in the pathogenesis of DPN.
MATERIALS AND METHODS
The proliferation rate of Rat Schwann cell line RSC96 cells stimulated by different concentrations of Glu and PA were analyzed by CCK-8 assay. After the IC50 was detected for each drug, the RSC96 cells were divided into control, Glu, Glu+PA, PA, and BSA groups. The apoptosis of RSC96 cells in different groups were detected by flow cytometry. The effects of Glu and/or PA on endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways were determined by Western blot and qPCR.
RESULTS
Both Glu and PA showed similar inhibition on the proliferation of RSC96 cells in a dose-dependent manner. However, PA induced stronger apoptosis of RSC96 cells than glucose and significantly increased the levels of X-box-binding protein-1 (XBP1), C/EBP homologous protein (CHOP), and eIF2α phosphorylation, which are key proteins regulating endoplasmic reticulum (ER) stress-associated apoptotic signaling pathways. The combination of Glu and PA induced the strongest apoptosis in RSC96 cells and also activated ER stress-associated apoptotic signaling pathways. These results verified the synergistic effect of Glu and PA on inducing ER stress-associated apoptosis in RSC96 cells, and PA even induced stronger apoptosis in RSC96 cells than Glu.
CONCLUSIONS
The present research indicated that hyperglycemia and hyperlipidemia might exert a synergistic damage during the pathogenesis of DPN, suggesting that blood lipid control is as important as blood glucose control for DPN patients.
Topics: Animals; Apoptosis; Diabetic Neuropathies; Endoplasmic Reticulum Stress; Glucose; Humans; Palmitic Acid; Rats; Schwann Cells
PubMed: 35049031
DOI: 10.26355/eurrev_202201_27761 -
Calcified Tissue International May 2016Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced...
Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.
Topics: Absorptiometry, Photon; Animals; Biomarkers; Ceramides; Diet, High-Fat; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Male; Mice; Mice, Inbred C57BL; Obesity; Oleic Acid; Osteoblasts; Osteogenesis; Palmitic Acid
PubMed: 26758875
DOI: 10.1007/s00223-015-0097-z -
Tropical Animal Health and Production Sep 2022The present study determined the effect of supplementing palmitic acid (PA) and stearic acid (SA) on the nutrient intake, digestibility, and serum metabolites of dairy...
Nutrient intake, digestibility, and serum metabolites in dairy cows fed diets differing in starch concentration with palmitic acid or stearic acid supplementation postpartum.
The present study determined the effect of supplementing palmitic acid (PA) and stearic acid (SA) on the nutrient intake, digestibility, and serum metabolites of dairy cows fed two different starch levels during the postpartum period. Forty-four multiparous Holstein cows were used in a completed randomized block based on their parity and previous milk yield. Dietary treatments were arranged in a 2 × 2 arrangement with two dietary starch levels (HS: 260 g/kg of diet dry matter (DM) vs LS: 210 g/kg of diet DM) and two fat supplements rich in PA or SA at 15 g/kg of diet DM. Increasing the starch concentration of the postpartum diet improved organic matter (OM), ether extract (EE), crude protein (CP), and starch intake. Moreover, HS diets resulted in higher apparent digestibility of OM and CP but lower starch digestibility than LS diets. Feeding HS diets increased fecal starch output compared with LS diets. There was starch levels and FA supplements interaction for serum albumin and total antioxidant capacity (TAC), with higher concentrations in HSSA and LSPA compared to HSPA and LSSA. Significant correlations between performance and blood metabolites were observed in weeks 3 and 4. In week 3, a negative correlation was observed between serum TAC with milk protein (r = - 0.51) and lactose percentage (r = - 0.49) in the HS diet. However, non-esterified FA was correlated with the fat to protein ratio in the LS diet (r = 0.54). Moreover, in week 4, serum TAC was negatively related to the body condition score of the cows fed LS diet (r = 0.50), while there was no relationship for cows fed HS diets. In conclusion, feeding HS diets to postpartum cows increased nutrient intake and the digestibility of OM and CP compared with LS diets. The addition of SA to the HS diet may be more beneficial than PA in improving the oxidative status of dairy cows in the postpartum period.
Topics: Animal Feed; Animals; Cattle; Diet; Dietary Supplements; Digestion; Eating; Female; Lactation; Palmitic Acid; Postpartum Period; Pregnancy; Starch; Stearic Acids
PubMed: 36076113
DOI: 10.1007/s11250-022-03296-3 -
The Journal of Nutrition Apr 2024Glycerol-3-phosphate acyltransferase (GPAT) activity is correlated with obesity and insulin resistance in mice and humans. However, insulin resistance exists in people...
BACKGROUND
Glycerol-3-phosphate acyltransferase (GPAT) activity is correlated with obesity and insulin resistance in mice and humans. However, insulin resistance exists in people with normal body weight, and individuals with obesity may be metabolically healthy, implying the presence of complex pathophysiologic mechanisms underpinning insulin resistance.
OBJECTIVE
We asked what conditions related to GPAT1 must be met concurrently for hepatic insulin resistance to occur.
METHODS
Mouse hepatocytes were overexpressed with GPATs via adenoviral infection or exposed to high or low concentrations of glucose. Glucose production by the cells and phosphatidic acid (PA) content in the cells were assayed, GPAT activity was measured, relative messenger RNA expressions of sterol-regulatory element-binding protein 1c (SREBP1c), carbohydrate response element-binding protein (ChREBP), and GPAT1 were analyzed, and insulin signaling transduction was examined.
RESULTS
Overexpressing GPAT1 in mouse hepatocytes impaired insulin's suppression of glucose production, together with an increase in both N-ethylmaleimide-resistant GPAT activity and the content of di-16:0 PA. Akt-mediated insulin signaling was inhibited in hepatocytes that overexpressed GPAT1. When the cells were exposed to high-glucose concentrations, insulin suppression of glucose production was impaired, and adding palmitic acid exacerbated this impairment. High-glucose exposure increased the expression of SREBP1c, ChREBP, and GPAT1 by ∼2-, 5-, and 5.7-fold, respectively. The addition of 200 mM palmitic acid or linoleic acid to the culture media did not change the upregulation of expression of these genes by high glucose. High-glucose exposure increased di-16:0 PA content in the cells, and adding palmitic acid further increased di-16:0 PA content. The effect was specific to palmitic acid because linoleic acid did not show these effects.
CONCLUSION
These data demonstrate that high-GPAT1 activity, whether induced by glucose exposure or acquired by transfection, and abundant palmitic acid can impair insulin's ability to suppress hepatic glucose production in primary mouse hepatocytes.
Topics: Animals; Mice; Glucose; Glycerol-3-Phosphate O-Acyltransferase; Hepatocytes; Insulin; Insulin Resistance; Insulin, Regular, Human; Linoleic Acid; Liver; Obesity; Palmitic Acid
PubMed: 38354952
DOI: 10.1016/j.tjnut.2024.02.004 -
Journal of Oleo Science Sep 2016Incorporations of nature fatty acids which were palmitic acid and stearic acid into the end positions of soybean oils were done using sn-1,3 specific immobilised lipase...
Incorporations of nature fatty acids which were palmitic acid and stearic acid into the end positions of soybean oils were done using sn-1,3 specific immobilised lipase from Rhizomucor miehei at different ratios in order to produce symmetrical triglycerides without changing the fatty acids at sn-2 position. The optimum ratio for the process was 25:75 w/w. There were 19.2% increase of SFA for P25 and 16% increase for S25 at the sn-1,3 positions. The research findings indicated that the structured lipids produced from enzymatic interesterification possessed a higher oxidative stability than soybean oil. The newly formed structured lipids (SUS type) could be good sources for various applications in food industry.
Topics: Enzymes, Immobilized; Esterification; Lipase; Palmitic Acid; Rhizomucor; Soybean Oil; Stearic Acids
PubMed: 27477075
DOI: 10.5650/jos.ess16097 -
International Journal of Molecular... Dec 2019The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de...
The outermost barrier layer of the skin is the stratum corneum (SC), which consists of corneocytes embedded in a lipid matrix. Biosynthesis of barrier lipids occurs de novo in the epidermis or is performed with externally derived lipids. Hence, in vitro developed human skin equivalents (HSEs) are developed with culture medium that is supplemented with free fatty acids (FFAs). Nevertheless, the lipid barrier formation in HSEs remains altered compared to native human skin (NHS). The aim of this study is to decipher the role of medium supplemented saturated FFA palmitic acid (PA) on morphogenesis and lipid barrier formation in HSEs. Therefore, HSEs were developed with 100% (25 μM), 10%, or 1% PA. In HSEs supplemented with reduced PA level, the early differentiation was delayed and epidermal activation was increased. Nevertheless, a similar SC lipid composition in all HSEs was detected. Additionally, the lipid organization was comparable for lamellar and lateral organization, irrespective of PA concentration. As compared to NHS, the level of monounsaturated lipids was increased and the FFA to ceramide ratio was drastically reduced in HSEs. This study describes the crucial role of PA in epidermal morphogenesis and elucidates the role of PA in lipid barrier formation of HSEs.
Topics: Cell Differentiation; Cells, Cultured; Ceramides; Epidermal Cells; Epidermis; Fatty Acids, Nonesterified; Humans; Keratinocytes; Lipid Metabolism; Lipids; Lipogenesis; Morphogenesis; Palmitic Acid; Skin; Skin, Artificial
PubMed: 31810180
DOI: 10.3390/ijms20236069 -
International Journal of Molecular... Aug 2023Various pathological alterations, including lipid-deposition-induced comparative cardiac lipotoxicity, contribute to cardiac aging in the failing heart. A decline in...
Various pathological alterations, including lipid-deposition-induced comparative cardiac lipotoxicity, contribute to cardiac aging in the failing heart. A decline in endogenous myogenin proteins can lead to the reversal of muscle cell differentiation and the creation of mononucleated muscle cells. Myogenin may be a specific regulator of adaptive responses to avoid pathological hypertrophy in the heart. Hence, it is important to understand the regulation of myogenin expression and functions in response to exposure to varied stresses. In this study, we first examined and verified the cytotoxic effect of palmitic acid on H9c2 cells. The reduction in mRNA and protein expression by palmitic acid was independent of the effect of glucose. Meanwhile, the induction of and mRNAs and proteins by palmitic acid was dependent on the presence of glucose. In addition, palmitic acid failed to disrupt cell cycle progression when H9c2 cells were treated with no glucose. Next, we examined the functional role of myogenin in palmitic-acid-treated H9c2 cells and found that myogenin may be involved in palmitic-acid-induced mitochondrial and cytosolic ROS generation, cellular senescence, and mitochondrial membrane potential. Finally, the GSE150059 dataset was deposited in the Gene Expression Omnibus website and the dataset was further analyzed via the molecular microscope diagnostic system (MMDx), demonstrating that many heart transplant biopsies currently diagnosed as no rejection have mild molecular-antibody-mediated rejection-related changes. Our data show that the expression levels of were lower than the average level in the studied population. Combining these results, we uncover part of the functional role of myogenin in lipid- and glucose-induced cardiac cell stresses. This finding provides valuable insight into the differential role of fatty-acid-associated gene expression in cardiovascular tissues. Additionally, the question of whether this gene expression is regulated by myogenin also highlights the usefulness of a platform such as MMDx-Heart and can help elucidate the functional role of myogenin in heart transplantation.
Topics: Palmitic Acid; Myogenin; Heart Transplantation; Heart
PubMed: 37685838
DOI: 10.3390/ijms241713031