Increasing palmitic acid and reducing stearic acid content of supplemental fatty acid blends improves production performance of mid-lactation dairy cows.

We determined the effects of altering the ratio of palmitic (C16:0) and stearic (C18:0) acids in supplemental fatty acid (FA) blends on production responses of mid-lactation dairy cows. Twenty-four multiparous Holstein cows (mean ± standard deviation; 47.1 ± 5.8 kg of milk yield, 109 ± 23 DIM) were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design with 21-d periods. Treatments were a control diet not supplemented with FA (CON), and 3 diets incorporating 1.5% of dry matter (DM) FA supplement blends containing 30% C16:0 + 50% C18:0, 50% C16:0 + 30% C18:0, and 80% C16:0 + 10% C18:0. Additionally, the FA blends were balanced to contain 10% of oleic acid (cis-9 C18:1). The FA blends replaced soyhulls in the CON diet. Diets were formulated to contain (% of DM) 31.0% neutral detergent fiber, 27.0% starch, and 16.9% crude protein. The statistical model included the random effect of cow within square and the fixed effects of period, treatment, and their interaction. Preplanned contrasts included CON versus overall effect of FA supplementation and the linear and quadratic effects of increasing C16:0 in FA blends. Overall FA treatment had no effect on dry matter intake (DMI), but increasing C16:0 linearly increased DMI. Compared with CON, overall FA treatment increased yields of milk, 3.5% of fat-corrected milk, energy-corrected milk, and milk fat but did not affect milk protein yield. Increasing C16:0 linearly increased milk fat yield and tended to linearly increase the yields of 3.5% of fat-corrected milk and energy-corrected milk. Fatty acid supplementation decreased the yield of de novo milk FA but increased yields of mixed and preformed milk FA compared with CON. Increasing C16:0 in FA treatments did not affect the yield of de novo milk FA, linearly increased the yield of mixed, and decreased the yield of preformed milk FA. In summary, feeding FA supplements containing C16:0 and C18:0 increased milk production responses with no effect on DMI compared with a control diet. Mid-lactation cows producing ∼40 to 50 kg/d milk yield responded best to increasing supplemental C16:0 in FA supplements, demonstrating that FA supplements higher in C16:0 and limited in C18:0 improves production responses.

Stearic acid promotes lipid synthesis through CD36/Fyn/FAK/mTORC1 axis in bovine mammary epithelial cells.

Stearic acid (C18:0, SA) is a saturated long-chain fatty acid (LCFA) that has a prominent function in lactating dairy cows. It is obtained primarily from the diet and is stored in the form of triacylglycerol (TAG) molecules. The transmembrane glycoprotein cluster of differentiation 36 (CD36) is also known as fatty acid translocase, but whether SA promotes lipid synthesis through CD36 and FAK/mTORC1 signaling is unknown. In this study, we examined the function and mechanism of CD36-mediated SA-induced lipid synthesis in bovine mammary epithelial cells (BMECs). SA-enriched supplements enhanced lipid synthesis and the FAK/mTORC1 pathway in BMECs. SA-induced lipid synthesis, FAK/mTORC1 signaling, and the expression of lipogenic genes were impaired by anti-CD36 and the CD36-specific inhibitor SSO, whereas overexpression of CD36 effected the opposite results. Inhibition of FAK/mTORC1 by TAE226/Rapamycin attenuated SA-induced TAG synthesis, inactivated FAK/mTORC1 signaling, and downregulated the lipogenic genes PPARG, CD36, ACSL1, SCD, GPAT4, LIPIN1, and DGAT1 at the mRNA and protein levels in BMECs. By coimmunoprecipitation and yeast two-hybrid screen, CD36 interacted directly with Fyn but not Lyn, and Fyn bound directly to FAK; FAK also interacted directly with TSC2. CD36 linked FAK through Fyn, and FAK coupled mTORC1 through TSC2 to form the CD36/Fyn/FAK/mTORC1 signaling axis. Thus, stearic acid promotes lipogenesis through CD36 and Fyn/FAK/mTORC1 signaling in BMECs. Our findings provide novel insights into the underlying molecular mechanisms by which LCFA supplements promote lipid synthesis in BMECs.

Effects of inoculation with four mycorrhizal species on seed phenolic and fatty acids of sesame plants grown under different irrigation regimes.

This study evaluated the interaction effects of irrigation level (well-watered and water stress conditions) and inoculation by different mycorrhizal species (non-inoculated, Funneliformis mosseae, Rhizophagus irregularis, Claroideoglomus claroideum, and Glomus fasciculatum) on mycorrhizal colonization, antioxidant activity, seed yield and oil quality of two sesame cultivars (Yekta and Naz). Water deficit decreased mycorrhizal colonization, seed yield and oil concentration but increased antioxidant activity and seed total phenol and flavonoid concentrations. However, mycorrhizal inoculation increased antioxidant activity, seed yield, oil concentration and total phenolic and flavonoids. The lowest reduction by water stress and the highest increase by inoculation in seed yield were observed in Naz plants inoculated by Cl. claroideum. Principal component analysis showed the highest differentiation effect of water stress compared to mycorrhizal inoculation on both cultivars, indicating the relative sensitivity of the two cultivars to water deficit. However, the application of different species of mycorrhizal fungi versus the non-inoculation conditions was somewhat discriminative. In terms of fatty acids, in most cases, water stress increased oleic, palmitic and stearic acids and decreased linoleic and linolenic acids but inoculation increased oleic and linoleic acids and decreased linolenic, palmitic and stearic acids. Regarding phenolic and flavonoids components, the contents of chlorogenic and caffeic acids were increased by water stress but no consistent trend was noted in response to water stress for the other compounds. Mycorrhizal inoculation generally decreased chlorogenic acid but increased gallic, caffeic, p-coumaric, and ferulic acids. In conclusion, the results of the present study may help to increase the level of valuable compounds in sesame for further pharmaceutical purposes under water stress conditions and mycorrhizal symbiosis.

Overexpression of miR-297b-5p in Mouse Insulin-Secreting Cells Promotes Metformin-Mediated Protection Against Stearic Acid-Induced Senescence by Targeting Igf1r.

BACKGROUND: A long-term consumption of saturated fat significantly increases the concentration of saturated fatty acids in serum, which accelerates the appearance of senescence markers in ß-cells and leads to their dysfunction. An understanding of the mechanisms underlying ß-cell senescence induced by stearic acid and the exploration of effective agents preventing it remains largely unclear. Here, we aimed to investigate the protective effect of metformin against stearic acid-treated ß-cell senescence and to assess the involvement of miR-297b-5p in this process. METHODS: To identify senescence, we measured senescence-associated ß-galactosidase activity and the expression of senescence-related genes. Gain and loss of function approaches were applied to explore the role of miR-297b-5p in stearic acid-induced ß-cell senescence. Bioinformatics analysis and a luciferase activity assay were used to predict the downstream targets of miR-297b-5p. RESULTS: Stearic acid markedly induced senescence and suppressed miR-297b-5p expression in mouse ß-TC6 cells, which were significantly alleviated by metformin. After transfection of miR-297b-5p mimics, stearic acid-evoked ß-cell senescence was remarkably prevented. Insulin-like growth factor-1 receptor was identified as a direct target of miR-297b-5p. Inhibition of the insulin-like growth factor-1 receptor prevented stearic acid-induced ß-cell senescence and dysfunction. Moreover, metformin alleviates the impairment of the miR-297b-5p inhibitor in ß-TC6 cells. Additionally, long-term consumption of a high-stearic-acid diet significantly increased senescence and reduced miR-297b-5p expression in mouse islets. CONCLUSIONS: These findings imply that metformin alleviates ß-cell senescence by stearic acid through upregulating miR-297b-5p to suppress insulin-like growth factor-1 receptor expression, thereby providing a potential target to not only prevent high fat-diet-induced ß-cell dysfunction but also for metformin therapy in type 2 diabetes.

Altering palmitic acid and stearic acid ratios in the diet of early-lactation Holsteins under heat stress: Feed intake, digestibility, feeding behavior, milk yield and composition, and plasma metabolites.

The objective of this study was to evaluate the effects of varying the ratio of dietary palmitic (C16:0; PA) and stearic (C18:0; SA) acids on nutrient digestibility, production, and blood metabolites of early-lactation Holsteins under mild-to-moderate heat stress. Eight multiparous Holsteins (body weight = 589 ± 45 kg; days in milk = 51 ± 8 d; milk production = 38.5 ± 2.4 kg/d; mean ± standard deviation) were used in a duplicated 4 × 4 Latin square design (21-d periods inclusive of 7-d data collection). The PA (88.9%)- and SA (88.5%)-enriched fat supplements, either individually or in combination, were added to diets at 2% of dry matter (DM) to formulate the following treatments: (1) 100PA:0SA (100% PA + 0% SA), (2) 66PA:34SA (66% PA + 34% SA), (3) 34PA:66SA (34% PA + 66% SA), and (4) 0PA:100SA (0% PA + 100% SA). Diets offered, in the form of total mixed rations, were formulated to be isonitrogenous (crude protein = 17.2% of DM) and isocaloric (net energy for lactation = 1.69 Mcal/kg DM), with a forage-to-concentrate ratio of 40:60. Ambient temperature-humidity index averaged 72.9 throughout the experiment, suggesting that cows were under mild-to-moderate heat stress. No differences in DM intake across treatments were detected (mean 23.5 ± 0.64 kg/d). Increasing the dietary proportion of SA resulted in a linear decrease in total-tract digestibility of total fatty acids, but organic matter, DM, neutral detergent fiber, and crude protein digestibilities were not different across treatments. Decreasing dietary PA-to-SA had no effect on the time spent eating (340 min/d), rumination (460 min/d), and chewing (808 min/d). As dietary PA-to-SA decreased, milk fat concentration and yield decreased linearly, resulting in a linear decrease of 3.5% fat-corrected milk production and milk fat-to-protein ratio. Feed efficiency expressed as kg 3.5% fat-corrected milk/kg DM intake decreased linearly with decreasing the proportion of PA-to-SA in the diet. Treatments had no effect on milk protein and lactose content. A linear increase in de novo and preformed fatty acids was identified as the ratio of PA to SA decreased, while PA and SA concentrations of milk fat decreased and increased linearly, respectively. A linear reduction in blood nonesterified fatty acids and glucose was detected as the ratio of PA to SA decreased. Insulin concentration increased linearly from 10.3 in 100PA:0SA to 13.1 µIU/mL in 0PA:100SA, whereas blood ß-hydroxybutyric acid was not different across treatments. In conclusion, the heat-stressed Holsteins in early-lactation phase fed diets richer in PA versus SA produced greater fat-corrected milk and were more efficient in converting feed to fat-corrected milk.

Volatile Compounds, Fatty Acids Constituents, and Antimicrobial Activity of Cultured Spirulina (Arthrospira fusiformis) Isolated from Lake Mariout in Egypt.

In this study, Arthrospira fusiformis previously isolated from Lake Mariout (Alexandria, Egypt) was cultivated in the laboratory using a medium for pharmaceutical grade Arthrospira, named as Amara and Steinbüchel medium. Hot water extract of the Egyptian Spirulina was prepared by autoclaving dried biomass in distilled water at 121°C for 15 min. This algal water extract was analyzed by GC-MS to evaluate its volatile compounds and fatty acids composition. The antimicrobial activity of phycobiliprotein extract from Arthrospira fusiformis using phosphate buffer was evaluated against thirteen microbial strains (two Gram-positive bacteria, eight Gram-negative bacteria, one yeast, and two filamentous fungi). The major components of fatty acids in the hot extract of Egyptian A. fusiformis were hexadecanoic acid (palmitic acid, 55.19%) and octadecanoic acid (stearic acid, 27.14%). The main constituents of its volatile compounds were acetic acid (43.33%) and oxalic acid (47.98%). The most potent antimicrobial effect of phycobiliprotein extract was obtained against two Gram-negative bacteria Salmonella typhi and Proteus vulgaris, filamentous fungus Aspergillus niger, and the pathogenic yeast Candida albicans (all of which showed MIC values of 58.1 µg/ml). Escherichia coli and Salmonella typhimurium come second in their susceptibility to the phycobiliprotein extract from Arthrospira fusiformis and Serratia marcescens and Aspergillus flavus are the least in susceptibility, with MIC values of 116.2 and 232.5 µg/ml, respectively, while phycobiliprotein extract has no antibacterial effect on methicillin-resistant as well as susceptible Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Shigella sonnei. These findings confirmed the nutritional value of Egyptian A. fusiformis isolated from Lake Mariout and suggest the potential use of this strain as an ingredient in the cooking of some foods to increase the level of stearic acid and palmitic acid. Moreover, its effective antibacterial activities against some important and highly resistant to antibiotics bacterial pathogens in addition to its antifungal effects recommend the therapeutic use of its biomass.

Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa.

BACKGRUOUND: Chronic exposure to elevated levels of saturated fatty acids results in pancreatic ß-cell senescence. However, targets and effective agents for preventing stearic acid-induced ß-cell senescence are still lacking. Although melatonin administration can protect ß-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse ß-cells and elucidated the possible role of microRNAs in this process. METHODS: ß-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated ß-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked ß-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. RESULTS: Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR- 8114 expression in both mouse islets and ß-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced ß-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected ß-cells. CONCLUSION: These data demonstrate that melatonin protects against stearic acid-induced ß-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced ß-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.

Exploring the effect of estrogen on Candida albicans hyphal cell wall glycans and ergosterol synthesis.

Increased levels of 17-ß estradiol (E2) due to pregnancy in young women or to hormonal replacement therapy in postmenopausal women have long been associated with an increased risk of yeast infections. Nevertheless, the effect underlying the role of E2 in Candida albicans infections is not well understood. To address this issue, functional, transcriptomic, and metabolomic analyses were performed on C. albicans cells subjected to temperature and serum induction in the presence or absence of E2. Increased filament formation was observed in E2 treated cells. Surprisingly, cells treated with a combination of E2 and serum showed decreased filament formation. Furthermore, the transcriptomic analysis revealed that serum and E2 treatment is associated with downregulated expression of genes involved in filamentation, including HWP1, ECE1, IHD1, MEP1, SOD5, and ALS3, in comparison with cells treated with serum or estrogen alone. Moreover, glucose transporter genes HGT20 and GCV2 were downregulated in cells receiving both serum and E2. Functional pathway enrichment analysis of the differentially expressed genes (DEGs) suggested major involvement of E2 signaling in several metabolic pathways and the biosynthesis of secondary metabolites. The metabolomic analysis determined differential secretion of 36 metabolites based on the different treatments' conditions, including structural carbohydrates and fatty acids important for hyphal cell wall formation such as arabinonic acid, organicsugar acids, oleic acid, octadecanoic acid, 2-keto-D-gluconic acid, palmitic acid, and steriacstearic acid with an intriguing negative correlation between D-turanose and ergosterol under E2 treatment. In conclusion, these findings suggest that E2 signaling impacts the expression of several genes and the secretion of several metabolites that help regulate C. albicans morphogenesis and virulence.

Stearic acid prevent alcohol-induced liver damage by regulating the gut microbiota.

The pathological characteristics of alcohol-associated liver damage (ALD) mainly include liver lipid accumulation, which subsequently leads to alcohol-associated steatohepatitis, fibrosis and cirrhosis. Dietary factors such as alcohol and fat may contribute to the development of ALD. A chronic alcohol-fed mouse model was used to investigate the effect of fatty acids in Jinhua ham on ALD. The fatty acids in Jinhua ham could prevent the occurrence of ALD from chronic alcohol consumption. In addition, the fatty acids in Jinhua ham with liver protective activity were long-chain saturated fatty acids (LCSFAs), including palmitic acid and stearic acid. In contrast, long-chain polyunsaturated fatty acids aggravated the pathogenesis of ALD. Furthermore, the mechanism underlying the prevention of ALD by fatty acids in Jinhua ham was ascribed to increasing relative abundances of Akkermansia muciniphila and Lactobacillus in the gut, which were beneficial to regulating intestinal homeostasis, ameliorating intestinal barrier dysfunction and reducing alcohol-associated hepatitis and oxidative stress damage. This study demonstrated that dietary supplementation with saturated fatty acids could prevent or mitigate ALD by regulating the gut microbiota (GM) and improving the intestinal barrier, while provided a more affordable dietary intervention strategy for the prevention of ALD.

Palmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro.

The intake of food with high levels of saturated fatty acids (SatFAs) is associated with the development of obesity and insulin resistance. SatFAs, such as palmitic (PA) and stearic (SA) acids, have been shown to accumulate in the hypothalamus, causing several pathological consequences. Autophagy is a lysosomal-degrading pathway that can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Previous studies showed that PA impairs macroautophagy function and insulin response in hypothalamic proopiomelanocortin (POMC) neurons. Here, we show in vitro that the exposure of POMC neurons to PA or SA also inhibits CMA, possibly by decreasing the total and lysosomal LAMP2A protein levels. Proteomics of lysosomes from PA- and SA-treated cells showed that the inhibition of CMA could impact vesicle formation and trafficking, mitochondrial components, and insulin response, among others. Finally, we show that CMA activity is important for regulating the insulin response in POMC hypothalamic neurons. These in vitro results demonstrate that CMA is inhibited by PA and SA in POMC-like neurons, giving an overview of the CMA-dependent cellular pathways that could be affected by such inhibition and opening a door for in vivo studies of CMA in the context of the hypothalamus and obesity.

Nanostructured Lipid Carriers Can Enhance Oral Absorption of Khellin, a Natural Pleiotropic Molecule.

A novel formulation based on nanostructured lipid carriers (NLCs) was developed to increase solubility and intestinal absorption of khellin. K-NLCs were prepared with stearic acid, hempseed oil, Brij S20, and Labrafil M 1944 CS, using the emulsification-ultrasonication method. Developed nanoparticles were chemically and physically characterized by liquid chromatography, light scattering techniques, and electron microscopy. The size, about 200 nm, was optimal for oral delivery, and the polydispersity index (around 0.26), indicated high sample homogeneity. Additionally, K-NLCs showed a spherical morphology without aggregation by microscopic analysis. The encapsulation efficiency of khellin was about 55%. In vitro release studies were carried out in media with different pH to mimic physiological conditions. K-NLCs were found to be physically stable in the simulated gastric and intestinal fluids, and they preserved about 70% of khellin after 6 h incubation. K-NLCs were also successfully lyophilized testing different lyoprotectants, and obtained freeze-dried K-NLCs demonstrated good shelf life over a month. Lastly, permeability studies on Caco-2 cells were performed to predict khellin passive diffusion across the intestinal epithelium, demonstrating that nanoparticles increased khellin permeability by more than two orders of magnitude. Accordingly, developed NLCs loaded with khellin represent a versatile formulation with good biopharmaceutical properties for oral administration, possibly enhancing khellin's bioavailability and therapeutic effects.

Effect of calcium stearate as a lubricant and catalyst on the thermal degradation of poly(3-hydroxybutyrate).

Poly(3-hydroxybutyrate) (PHB) is a promising substitute to petroleum-based polymers in packaging and biomedical applications provided that its melt processability and degradability are improved. A new method to control the properties of PHB by using cheap calcium stearate (CS) as a lubricant and decomposition catalyst in melt-mixed PHB-CS compounds was first used. CS is composed of a metallic cation, which promotes PHB degradation, and a hydrophobic anion that improves the compatibility with PHB and processability. An environmentally friendly melt mixing technique was employed to obtain the PHB-CS compounds. Incorporation of 0.5 or 5 wt% CS reduced the melt viscosity and molecular weight of PHB, decreased the melting temperature with up to 5 °C, the crystallization temperature with more than 25 °C, and the degradation temperature with 15 and 40 °C, respectively. In small amounts (0.05 wt%), CS improved the processability and mechanical properties of PHB. In higher amount (0.5 wt%), CS slightly improved the Young's modulus, reduced the tensile strength and enhanced degradation. A better control of thermal and mechanical properties of PHB is, thus, possible by using different CS amount and processing conditions. These results are relevant for PHB application in the context of the global transition to biodegradable packaging.

Effect of regioisomers of hydroxystearic acids as peroxisomal proliferator-activated receptor agonists to boost the anti-ageing potential of retinoids.

INTRODUCTION: We report on the in vitro and ex vivo effects of chiral (R)-10-hydroxystearic acid (10-HSA) compared with other mono-hydroxystearic acid regioisomers and stearic acid (SA) together with its benefit when combined with retinol. METHODS: Following treatment with hydroxystearic acids peroxisomal proliferator-activated receptor alpha (PPARα) activity was determined in a luciferase reporter gene assay, collagen type I was assessed in primary human dermal fibroblasts by immunohistochemistry, modification of the intracellular fibroblast collagen proteome was studied by mass-spectrometry-based proteomics and collagen type III was assessed by immunohistochemistry on human ex vivo skin. RESULTS: 10-HSA was the most effective PPARα agonist (15.7× induction; p < 0.001), followed by 9-HSA (10.1× induction) and then 12-HSA (4.9× induction) with 17-HSA (1.7× induction) being similar to the effects of stearic acid (1.8× induction). Collagen type I levels were increased in primary human fibroblasts by 2.12× and 1.56× for 10-HSA and 9-HSA, respectively, in vitro with the10-HSA being significant (p < 0.05), whereas 12-HSA and SA had no statistical effect over the untreated control. 10-HSA and 12-HSA modified the intracellular fibroblast collagen proteome slightly with significant increases in collagen alpha-1 (VI) and alpha-3 (VI) proteins but only 10-HSA increased levels of collagen alpha-2 (V), alpha-1 (III), alpha-1 (I) and alpha-2 (I) (all p < 0.05) with the increases being significantly different between 10-HSA and 12-HSA for collagen alpha-1 (I), collagen-3 (VI) and collagen alpha-2 (I) (p < 0.01). Collagen type III in ex vivo skin was increased +47% (p < 0.05) by 0.05% (1.7 mM) retinol, +70% (p < 0.01) by 0.01% (0.33 mM) 10-HSA and the combination increased levels by +240% (p < 0.01 for either ingredient). CONCLUSION: Chiral (R)-10-HSA has been shown to be superior to 9, 12 and 17-HSA as a PPARα agonist. Moreover, 10-HSA stimulated collagen synthesis in monolayer fibroblast culture as assessed by proteomics and immunohistochemically. Furthermore, we also show the synergistic effects of 10-HSA with retinol on collagen III synthesis in skin explants. These results further highlight the efficacy of 10-HSA as a cosmetically acceptable PPARα agonist and anti-ageing ingredient.

INTRODUCTION: Nous rapportons les effets in vitro et ex vivo de l'acide chiral (R)-10-hydroxystéarique (10-HSA) par rapport à d'autres régioisomères d'acide mono-hydroxystéarique et à l'acide stéarique (SA) ainsi que ses avantages lorsqu'il est associé au rétinol. MÉTHODES: Après un traitement avec des acides hydroxystéariques, l'activité du récepteur alpha activé par les proliférateurs peroxysomaux (PPARα) a été déterminée dans un test du gène rapporteur de la luciférase, le collagène de type I a été évalué dans les fibroblastes dermiques humains primaires par immunohistochimie, la modification du protéome du collagène des fibroblastes intracellulaires a été étudiée par spectrométrie de masse. La protéomique et le collagène de type III ont été évalués par immunohistochimie sur la peau humaine ex vivo. RÉSULTATS: la 10-HSA était l'agoniste PPARα le plus efficace (induction 15,7X ; p<0,001), suivi de la 9-HSA (induction 10,1X) puis de la 12-HSA (induction 4,9X) avec la 17-HSA (induction 1,7X) étant similaire aux effets de l'acide stéarique (induction 1,8X). Les niveaux de collagène de type I ont été augmentés dans les fibroblastes humains primaires de 2,12X et 1,56X pour la 10-HSA et la 9-HSA respectivement in vitro, la 10-HSA étant significative (p<0,05) : alors que la 12-HSA et la SA n'ont eu aucun effet statistique sur le témoin non traité. La 10-HSA et la 12-HSA ont légèrement modifié le protéome du collagène des fibroblastes intracellulaires avec des augmentations significatives des protéines de collagène alpha-1 (VI) et alpha-3 (VI), mais seule la 10-HSA a augmenté les niveaux de collagène alpha-2 (V), alpha -1 (III), alpha-1 (I) et alpha-2 (I) (tous p<0,05) avec des augmentations significativement différentes entre 10-HSA et 12-HSA pour le collagène alpha-1 (I), le collagène- 3 (VI) et Collagène alpha-2 (I) (p<0,01). Le collagène de type III dans la peau ex vivo a augmenté de +47 % (p<0,05) de 0,05 % (1,7 mM) de rétinol, de +70 % (p<0,01) de 0,01 % (0,33 mM) de 10-HSA et la combinaison a augmenté les niveaux de +240 % (p<0,01 pour chaque ingrédient). CONCLUSION: La chiral (R)-10-HSA s'est avérée supérieure à 9, 12 et 17-HSA en tant qu'agoniste de PPARα. De plus, la 10-HSA a stimulé la synthèse de collagène dans la culture de fibroblastes monocouche telle qu'évaluée par protéomique et immunohistochimique. De plus, nous montrons également les effets synergiques de la 10-HSA avec le rétinol sur la synthèse du collagène III dans les explants de peau. Ces résultats soulignent en outre l'efficacité de la 10-HSA en tant qu'agoniste de PPARα et ingrédient anti-âge cosmétiquement acceptable.

Effect of stearic acid on the microstructural, rheological and 3D printing characteristics of rice starch.

The aim of this study was to investigate the changes of the microstructural, rheological and printing properties of rice starch-stearic acid (SA) paste during the hot-extrusion 3D printing (HE-3DP). The results showed that starch chains could complex with SA to form V-type crystalline structure and its molecular kinematic behaviors were changed under shear force, and crystalline structure were then embedded and rearranged to constitute an ordered sea-island structure, thus improving the rigidity and dynamic storage modulus of network structure, leading to the increased layer number. Interestingly, with the increase of SA addition, the network structure became weakened and the viscosity decreased which might due to the destroyed continuity and the breaking of entanglement and hydrogen bonding between starch chains, and finally impairing the printing accuracy of objects. Overall, this study provided important information for the application of lipid in the preparation of starch-based food by HE-3DP.

Inhibition of lncRNA TCONS_00077866 Ameliorates the High Stearic Acid Diet-Induced Mouse Pancreatic ß-Cell Inflammatory Response by Increasing miR-297b-5p to Downregulate SAA3 Expression.

Long-term consumption of a high-fat diet increases the circulating concentration of stearic acid (SA), which has a potent toxic effect on ß-cells, but the underlying molecular mechanisms of this action have not been fully elucidated. Here, we evaluated the role of long noncoding (lnc)RNA TCONS_00077866 (lnc866) in SA-induced ß-cell inflammation. lnc866 was selected for study because lncRNA high-throughput sequencing analysis demonstrated it to have the largest fold-difference in expression of five lncRNAs that were affected by SA treatment. Knockdown of lnc866 by virus-mediated shRNA expression in mice or by Smart Silencer in mouse pancreatic ß-TC6 cells significantly inhibited the SA-induced reduction in insulin secretion and ß-cell inflammation. According to lncRNA-miRNAs-mRNA coexpression network analysis and luciferase reporter assays, lnc866 directly bound to miR-297b-5p, thereby preventing it from reducing the expression of its target serum amyloid A3 (SAA3). Furthermore, overexpression of miR-297b-5p or inhibition of SAA3 also had marked protective effects against the deleterious effects of SA in ß-TC6 cells and mouse islets. In conclusion, lnc866 silencing ameliorates SA-induced ß-cell inflammation by targeting the miR-297b-5p/SAA3 axis. lnc866 inhibition may represent a new strategy to protect ß-cells against the effects of SA during the development of type 2 diabetes.

Raman Study on Lipid Droplets in Hepatic Cells Co-Cultured with Fatty Acids.

The purpose of the present study was to investigate molecular compositions of lipid droplets changing in live hepatic cells stimulated with major fatty acids in the human body, i.e., palmitic, stearic, oleic, and linoleic acids. HepG2 cells were used as the model hepatic cells. Morphological changes of lipid droplets were observed by optical microscopy and transmission electron microscopy (TEM) during co-cultivation with fatty acids up to 5 days. The compositional changes in the fatty chains included in the lipid droplets were analyzed via Raman spectroscopy and chemometrics. The growth curves of the cells indicated that palmitic, stearic, and linoleic acids induced cell death in HepG2 cells, but oleic acid did not. Microscopic observations suggested that the rates of fat accumulation were high for oleic and linoleic acids, but low for palmitic and stearic acids. Raman analysis indicated that linoleic fatty chains taken into the cells are modified into oleic fatty chains. These results suggest that the signaling pathway of cell death is independent of fat stimulations. Moreover, these results suggest that hepatic cells have a high affinity for linoleic acid, but linoleic acid induces cell death in these cells. This may be one of the causes of inflammation in nonalcoholic fatty liver disease (NAFLD).

Saturated Oxo Fatty Acids (SOFAs): A Previously Unrecognized Class of Endogenous Bioactive Lipids Exhibiting a Cell Growth Inhibitory Activity.

The discovery of novel bioactive lipids that promote human health is of great importance. Combining "suspect" and targeted lipidomic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) approaches, a previously unrecognized class of oxidized fatty acids, the saturated oxo fatty acids (SOFAs), which carry the oxo functionality at various positions of the long chain, was identified in human plasma. A library of SOFAs was constructed, applying a simple green photochemical hydroacylation reaction as the key synthetic step. The synthesized SOFAs were studied for their ability to inhibit in vitro the cell growth of three human cancer cell lines. Four oxostearic acids (OSAs) were identified to inhibit the cell growth of human lung carcinoma A549 cells. 6OSA and 7OSA exhibited the highest cell growth inhibitory potency, suppressing the expression of both STAT3 and c-myc, which are critical regulators of cell growth and proliferation. Thus, naturally occurring SOFAs may play a role in the protection of human health.

A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.

AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors. RESULTS: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.

Chemical constituents from Urtica fissa stem and their inhibitory effects on α-glucosidase activity.

A new unsaturated fatty acid (E)-7,9-diene-11-carbonyl stearic acid (1) and a new lignan 8'-acetyl olivil (2), together with 14 known compounds (3-16), were isolated from the stem of Urtica fissa E. Pritz. Their structures were elucidated by spectroscopic and mass-spectrometric analyses. 8'-Acetyl olivil (2), (6 R,9R)-roseoside (15) and urticol-7-O-ß-d-glucopyrannoside (16) exhibited significant inhibition on α-glucosidase activities, with IC50 values less than 9 µM.