Accumulation Of Palmitic Acid Research Articles

Baicalein alleviates palmitic acid-induced endothelial cell dysfunction via inhibiting endoplasmic reticulum stress.

Endothelial cells play a critical role in maintaining vascular function and kinetic homeostasis, but excessive accumulation of palmitic acid (PA) may lead to endoplasmic reticulum stress and trigger endothelial cell dysfunction. Baicalin (BCL), a natural plant extract, has received widespread attention for its biological activities in anti-inflammation and anti-oxidative stress. However, the mechanism of BCL on PA-induced endothelial cell dysfunction is unclear. Therefore, the aim of this study was to investigate whether BCL could inhibit PA-induced endoplasmic reticulum stress and thus attenuate endothelial cell dysfunction. Human umbilical vein endothelial cells (HUVECs) were divided into Control, PA, PA + BCL-10 μM, PA + BCL-20 μM, and PA + BCL-50 μM groups. The PA group was treated with PA (200 μM), while the PA + BCL groups were co-treated with different concentrations of BCL (10 μM, 20 μM, 50 μM) for 24 hours. Cell viability was detected by MTT. Cell migration ability was determined by Transwell assay, apoptosis level by flow cytometry, and tube formation ability by tube formation assay. Finally, the levels of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and angiogenesis-related proteins (VEGFA and FGF2) were detected by western blot, MMP-9, as well as the protein levels of endoplasmic reticulum stress biomarkers (GRP78, CHOP, PERK, and ATF4). The results at the cellular level showed that cell viability, migration ability and tube formation ability of PA-induced HUVECs were significantly reduced, while apoptosis level was significantly increased. However, administration of different concentrations of BCL significantly enhanced PA-induced cell viability, migration ability and tube formation ability of HUVECs while inhibiting apoptosis. The results of protein levels showed that the protein levels of Bax and cleaved caspase-3 were observably up-regulated in the cells of the PA group, while the protein level of Bcl-2 was significantly down-regulated; compared with the PA group, the protein levels of Bax and cleaved caspase-3 were much lower and the Bcl-2 protein level was much higher in the PA + BCL group. Additionally, the protein levels of VEGFA, FGF2 and MMP-9 were raised and those of GRP78, CHOP, PERK and ATF4 were lowered in the PA + BCL group of cells in a concentration-dependent manner. BCL significantly attenuates PA-induced endothelial cell dysfunction by inhibiting endoplasmic reticulum stress.

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.

Tea polyphenols coating improves physiological properties, microstructure and chemical composition of cuticle to suppress quality deterioration of passion fruit during cold storage

The plant cuticle plays a crucial role in modulating postharvest quality and extending shelf life of horticultural crops. Passion fruit often suffers from quality degradation primarily due to peel wrinkling after harvest. Tea polyphenols (TPs) hold potential for enhancing postharvest preservation. However, the specific effects of TPs coating on preservation of passion fruit, as well as the underlying mechanisms involving cuticle regulation, have not been thoroughly investigated. This study demonstrated that treating ‘Qinmi no.9’ passion fruit with TPs at a concentration of 0.1 g L−1 significantly mitigates weight loss, maintains firmness, and reduces cell membrane permeability during storage at 10 °C. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed that TPs treatment notably enhances cuticle thickness and structural integrity. Furthermore, gas chromatography–mass spectrometry (GC–MS) and metabolomics analyses indicated that TPs treatment obviously promotes the accumulation of palmitic acid, stearic acid, and their derivatives—primarily 12-Octadecenoic acid and 10(E)-Octadecenoic acid—as well as increases the levels of 11-Octadecenoic acid, primary alcohols such as 1-Eicosanol, and long-chain alkanes (including C31 and C32 alkanes) in the fruit peel cuticle. These biochemical changes contribute to the quality maintenance of passion fruit during cold storage. The findings suggest that TPs treatment is a promising biological strategy for extending shelf life and mitigating quality degradation by regulating cuticle metabolism in postharvest passion fruit.

FADS2 confers SCD1 inhibition resistance to cancer cells by modulating the ER stress response

Stearoyl-CoA desaturase 1 (SCD1) is an attractive target for cancer therapy. However, the clinical efficacy of SCD1 inhibitor monotherapy is limited. There is thus a need to elucidate the mechanisms of resistance to SCD1 inhibition and develop new therapeutic strategies for combination therapy. In this study, we investigated the molecular mechanisms by which cancer cells acquire resistance to endoplasmic reticulum (ER) stress-dependent cancer cell death induced by SCD1 inhibition. SCD1 inhibitor-sensitive and -resistant cancer cells were treated with SCD1 inhibitors in vitro, and SCD1 inhibitor-sensitive cancer cells accumulated palmitic acid and underwent ER stress response-induced cell death. Conversely, SCD1-resistant cancer cells did not undergo ER stress response-induced cell death because fatty acid desaturase 2 (FADS2) eliminated the accumulation of palmitic acid. Furthermore, genetic depletion using siRNA showed that FADS2 is a key determinant of sensitivity/resistance of cancer cells to SCD1 inhibitor. A549 cells, an SCD1 inhibitor-resistant cancer cell line, underwent ER stress-dependent cancer cell death upon dual inhibition of SCD1 and FADS2. Thus, combination therapy with SCD1 inhibition and FADS2 inhibition is potentially a new cancer therapeutic strategy targeting fatty acid metabolism.

Regulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2

The cellular membrane in male meiotic germ cells contains a unique class of phospholipids and sphingolipids that is required for male reproduction. Here, we show that a conserved membrane fluidity sensor, AdipoR2, regulates the meiosis-specific lipidome in mouse testes by promoting the synthesis of sphingolipids containing very-long-chain polyunsaturated fatty acids (VLC-PUFAs). AdipoR2 upregulates the expression of a fatty acid elongase, ELOVL2, both transcriptionally and post-transcriptionally, to synthesize VLC-PUFA. The depletion of VLC-PUFAs and subsequent accumulation of palmitic acid in AdipoR2 knockout testes stiffens the cellular membrane and causes the invagination of the nuclear envelope. This condition impairs the nuclear peripheral distribution of meiotic telomeres, leading to errors in homologous synapsis and recombination. Further, the stiffened membrane impairs the formation of intercellular bridges and the germ cell syncytium, which disrupts the orderly arrangement of cell types within the seminiferous tubules. According to our findings we propose a framework in which the highly-fluid membrane microenvironment shaped by AdipoR2-ELOVL2 underpins meiosis-specific chromosome dynamics in testes.

Synergism of Fusobacterium periodonticum and N-nitrosamines promote the formation of EMT subtypes in ESCC by modulating Wnt3a palmitoylation.

N-Nitrosamine disinfection by-products (NAs-DBPs) have been well proven for its role in esophageal carcinogenesis. However, the role of intratumoral microorganisms in esophageal squamous cell carcinoma (ESCC) has not yet been well explored in the context of exposure to NAs-DBPs. Here, the multi-omics integration reveals F. periodonticum (Fp) as "facilitators" is highly enriched in cancer tissues and promotes the epithelial mesenchymal transition (EMT)-like subtype formation of ESCC. We demonstrate that Fp potently drives de novo synthesis of fatty acids, migration, invasion and EMT phenotype through its unique FadAL adhesin. However, N-nitrosomethylbenzylamine upregulates the transcription level of FadAL. Mechanistically, co-immunoprecipitation coupled to mass spectrometry shows that FadAL interacts with FLOT1. Furthermore, FLOT1 activates PI3K-AKT/FASN signaling pathway, leading to triglyceride and palmitic acid (PA) accumulation. Innovatively, the results from the acyl-biotin exchange demonstrate that FadAL-mediated PA accumulation enhances Wnt3A palmitoylation on a conserved cysteine residue, Cys-77, and promotes Wnt3A membrane localization and the translocation of β-catenin into the nucleus, further activating Wnt3A/β-catenin axis and inducing EMT phenotype. We therefore propose a "microbiota-cancer cell subpopulation" interaction model in the highly heterogeneous tumor microenvironment. This study unveils a mechanism by which Fp can drive ESCC and identifies FadAL as a potential diagnostic and therapeutic target for ESCC.

Temporal changes in muscle characteristics during growth in the goat

This study aimed to explore the temporal accumulative process of functional components and take insight into their dynamic regulatory metabolic pathways in the longissimus during growth in goats. Results showed that the intermuscular fat content, cross-sectional area and fast- to slow-switch fiber ratio of the longissimus were synchronously increased from d1 to d90. The dynamic profiles of functional components and transcriptomic pathways of the longissimus both exhibited two distinct phases during animal development. Expression of genes involved in de novo lipogenesis was increased from birth to weaning, leading to the accumulation of palmitic acid in the first phase. Accumulation of functional oleic acid, linoleic acid and linolenic acid in the second phase was dominatingly driven by enhancement in expression of genes related to fatty acid elongation and desaturation after weaning. A shift from serine to glycine production was observed after weaning, which was linked to the expression profile of genes involved in their interconversion. Our findings systematically reported the key window and pivotal targets of the functional components' accumulation process in the chevon.

English

The objective of this work was to analyze the growth of Scenedesmus acutus, Nannochloropsis oculata and Chlorella vulgaris at different temperatures (25, 30 and 38°C) in order to identify changes in lipid content, accumulation of neutral lipids and fatty acids profile. According to the results obtained, the temperature of 30°C does not affect the growth of the microalgae S. acutus, N. oculata and C. vulgaris; however, there is a greater amount of total lipids in S. acutus at 38°C, while for N. oculata and C. vulgaris, temperature variation does not affect the accumulation of total lipids. From the data obtained from the fatty acid profile, we observed a greater accumulation of palmitic acid followed by oleic acid. According to the cetane number, any temperature condition of any evaluated microalgae culture can be used for biodiesel production. The results suggest that a change in temperature during the growth of microalgae could be applied to enhance lipid production and to obtain fatty acids suitable for biodiesel production.    Key words: Chlorella vulgaris, Nannochloropsis oculata, Scenedesmus acutus, fatty acids, lipids, temperature.

Identification and Functional Characterization of Acyl-ACP Thioesterases B (GhFatBs) Responsible for Palmitic Acid Accumulation in Cotton Seeds.

In spite of increasing use in the food industry, high relative levels of palmitic acid (C16:0) in cottonseed oil imposes harmful effects on human health when overconsumed in the diet. The limited understanding of the mechanism in controlling fatty acid composition has become a significant obstacle for breeding novel cotton varieties with high-quality oil. Fatty acyl-acyl carrier protein (ACP) thioesterase B (FatBs) are a group of enzymes which prefer to hydrolyze the thioester bond from saturated acyl-ACPs, thus playing key roles in controlling the accumulation of saturated fatty acids. However, FatB members and their roles in cotton are largely unknown. In this study, a genome-wide characterization of FatB members was performed in allotetraploid upland cotton, aiming to explore the GhFatBs responsible for high accumulations of C16:0 in cotton seeds. A total of 14 GhFatB genes with uneven distribution on chromosomes were identified from an upland cotton genome and grouped into seven subfamilies through phylogenetic analysis. The six key amino acid residues (Ala, Trys, Ile, Met, Arg and Try) responsible for substrate preference were identified in the N-terminal acyl binding pocket of GhFatBs. RNA-seq and qRT-PCR analysis revealed that the expression profiles of GhFatB genes varied in multiple cotton tissues, with eight GhFatBs (GhA/D-FatB3, GhA/D-FatB4, GhA/D-FatB5, and GhA/D-FatB7) having high expression levels in developing seeds. In particular, expression patterns of GhA-FatB3 and GhD-FatB4 were positively correlated with the dynamic accumulation of C16:0 during cotton seed development. Furthermore, heterologous overexpression assay of either GhA-FatB3 or GhD-FatB4 demonstrated that these two GhFatBs had a high substrate preference to 16:0-ACP, thus contributing greatly to the enrichment of palmitic acid in the tested tissues. Taken together, these findings increase our understanding on fatty acid accumulation and regulation mechanisms in plant seeds. GhFatBs, especially GhA-FatB3 and GhD-FatB4, could be molecular targets for genetic modification to reduce palmitic acid content or to optimize fatty acid profiles in cotton and other oil crops required for the sustainable production of healthy edible oil.

Deficiency of peroxisomal NUDT7 stimulates de novo lipogenesis in hepatocytes

SummaryHere, we found that heterozygous null of peroxisomal Nudt7 (Nudt7+/−) induced the typical NAFLD features, i.e. increased levels of hepatic triglyceride (TG) and fatty acid (FA), infiltration of inflammatory cells, impaired glucose tolerance and insulin sensitivity, and stimulation of lipolysis from adipose tissue. Particularly, in Nudt7+/− hepatocytes, de novo lipogenesis (DNL) was significantly increased. Ingenuity pathway analysis (IPA) and KEGG pathway analysis of RNA sequencing data suggested the activation of PPAR signaling in the liver of Nudt7+/− mice. Moreover, accumulation of palmitic acid in Nudt7+/− hepatocyte increased the level of H3K4me3 on the promoters of PPARγ resulting in the activation of PPARγ and induced the DNL in the hepatocytes of Nudt7+/− mice. Moreover, we found that liraglutide significantly reduced typical NAFLD features induced by NUDT7 deficiency. Our data suggest that dysregulation of peroxisomal NUDT7 is responsible for upregulation of hepatic DNL by accumulation of palmitic acid and PPARγ activation.

Palmitoyl-CoA effect on cytochrome c release, a key process of apoptosis, from liver mitochondria of rat with sucrose diet-induced obesity

Cytochrome c (cyt-c) release from the mitochondria to the cytosol is a key process in the initiation of hepatocyte apoptosis involved in the progression of non-alcoholic fatty liver disease (NAFLD) to fibrosis, cirrhosis and hepatocellular carcinoma. Hepatocyte apoptosis may be related to lipotoxicity due to the accumulation of palmitic acid and palmitoyl-CoA (Pal-CoA). Therefore, the aim of this study is to examine whether Pal-CoA induces cyt-c release from liver mitochondria of sucrose-fed rat (SF). Pal-CoA-induced cyt-c release was sensitive to cyclosporine A indicating the involvement of the mitochondrial membrane permeability transition (mMPT). In addition, cyt-c release from SF mitochondria remains significantly lower than C mitochondria despite the increased rate of H2O2 generation in SF mitochondria. The decreased cyt-c release from SF may be also related to the increased proportion of the palmitic acid-enriched cardiolipin, due to the high availibilty of palmitic acid in SF liver. The enrichment of cardiolipin molecular species with palmitic acid makes cardiolipin more resistant to peroxidation, a mechanism involved in the dissociation of cyt-c from mitochondrial inner membrane. These results suggest that Pal-CoA may participate in the progression of NAFLD to more severe disease through mechanisms involving cyt-c release and mMPT, a key process of apoptosis.

Effect of docosahexaenoic acid plus insulin on atherosclerotic human endothelial cells

BackgroundAtherosclerosis is touted as one of the most critical consequences of diabetes mellitus indicated by local inflammation of endothelial cells. The Effect of Omega 3 fatty acids, mainly docosahexaenoic acid (DHA), has been investigated in cells after exposure to high doses of lipids. The current experiment aimed to address the modulatory effects of docosahexaenoic acid and insulin in palmitic-treated human endothelial cells.MethodsHuman umbilical vein endothelial cells were treated with 1 mM palmitic acid, 50 μM insulin, 50 μM docosahexaenoic acid, and their combination for 48 h. Cell survival rate and apoptosis were measured using MTT and flow cytometry assays. The Griess assay detected NO levels. Protein levels of TNF-α, IL-6, and NF-κB were studied using ELISA and immunofluorescence imaging. The expression of genes participating in atherosclerosis was monitored using PCR array analysis.ResultsOil Red O staining showed the inhibitory effect of DHA and insulin to reduce the intracellular accumulation of palmitic acid. Both DHA and Insulin blunted palmitic acid detrimental effects on HUVECs indicated by an increased survival rate (p < 0.05). The percent of apoptotic cells was decreased in palmitic-treated cells received insulin and DHA compared to palmitic-treated group (p < 0.05). Based on our data, DHA and Insulin diminished the production of all inflammatory cytokines, TNF-α, IL-6, and NF-κB, in palmitic-treated cells (p < 0.05). Similar to these data, NO production was also decreased in all groups treated with insulin and DHA compared to the palmitic-treated cells (p < 0.05). PCR array analysis revealed the modulatory effect of DHA and insulin on the expression of atherosclerosis-related genes pre-treated with palmitic acid compared to the control group (p < 0.05).ConclusionDHA and Insulin could alter the dynamic growth and dysfunctional activity of human endothelial cells after treatment with palmitic acid. Taken together, Omega 3 fatty acids, along with insulin, could dictate specific cell behavior in endothelial cells in vitro.

Palmitic Acid Promotes Virus Replication in Fish Cell by Modulating Autophagy Flux and TBK1-IRF3/7 Pathway.

Palmitic acid is the most common saturated fatty acid in animals, plants, and microorganisms. Studies highlighted that palmitic acid plays a significant role in diverse cellular processes and viral infections. Accumulation of palmitic acid was observed in fish cells (grouper spleen, GS) infected with Singapore grouper iridovirus (SGIV). The fluctuated content levels after viral infection suggested that palmitic acid was functional in virus-cell interactions. In order to investigate the roles of palmitic acid in SGIV infection, the effects of palmitic acid on SGIV induced cytopathic effect, expression levels of viral genes, viral proteins, as well as virus production were evaluated. The infection and replication of SGIV were increased after exogenous addition of palmitic acid but suppressed after knockdown of fatty acid synthase (FASN), of which the primary function was to catalyze palmitate synthesis. Besides, the promotion of virus replication was associated with the down-regulating of interferon-related molecules, and the reduction of IFN1 and ISRE promotor activities by palmitic acid. We also discovered that palmitic acid restricted TBK1, but not MDA5-induced interferon immune responses. On the other hand, palmitic acid decreased autophagy flux in GS cells via suppressing autophagic degradation, and subsequently enhanced viral replication. Together, our findings indicate that palmitic acid is not only a negative regulator of TBK1-IRF3/7 pathway, but also a suppressor of autophagic flux. Finally, palmitic acid promotes the replication of SGIV in fish cells.

Palmitic acid accumulation limits methane production in anaerobic co-digestion of fats, oils and grease with municipal wastewater sludge

Anaerobic co-digestion of fats, oils and grease (FOG) with municipal wastewater sludge offers the opportunity to increase methane yields; yet the impact of FOG on overall process dynamics and the associated microbial communities is not well understood. This study employed lab-scale batch anaerobic co-digestion assays to advance the understanding of the co-digestion process through studying the dynamics of formation and consumption of intermediates along the anaerobic digestion pathway and correlating these to temporal analysis of methanogenic activity as well as end-point microbial community structure. Methane production was delayed during sludge co-digestion with FOG, but not during digestion of sludge alone. Palmitic acid, a long-chain fatty acid (LCFA), accumulated during co-digestion to concentrations above 16 mM, resulting in a lag in methane production. Acetate, hydrogen, and formate, carbon and/or energy sources for methanogens during methane production, did not accumulate during the lag-phase. Expression of the mcrA gene, which encodes the methyl coenzyme M reductase alpha subunit necessary for catalyzing the final step of methanogenesis, increased when co-digesters were spiked with acetate during the lag-phase, indicating no direct total inhibition from palmitic acid to methanogenic activity in assays with a 23% FOG loading (based on total g VS). End-point microbial community analyses revealed distinct community structure and composition differences between co-digestion assays and controls, and between biological replicates with variable responses. The hydrogenotrophic methanogen genus Methanoculleus dominated adapted co-digesters, but not inhibited co-digesters suggesting its importance for adapting to FOG loadings. Palmitic acid accumulation resulting from distinct microbial community composition and structure thus characterizes stalled or inhibited FOG co-digesters.

Long-term hypercortisolism induces lipogenesis promoting palmitic acid accumulation and inflammation in visceral adipose tissue compared with HFD-induced obesity.

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity on white adipose tissue mass and distribution, by focusing on visceral adipose tissue (VAT) fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a noninvasive mouse model of hypercortisolism to compare GC-induced effects on adipose tissue with diet-induced obesity [high-fat diet (HFD) 45%] and control mice after 10 wk of treatment. Subcutaneous adipose tissue (SAT) and VAT mass and distribution were measured by nuclear magnetic resonance imaging (NMRI). Fatty acid composition in VAT was analyzed by NMR spectroscopy and gas chromatography. Gene expression of key enzymes involved in DNL was analyzed in liver and VAT. Macrophage infiltration markers and proinflammatory cytokines were measured by gene expression in VAT. HFD or GC treatment induced similar fat mass expansion with comparable distribution between SAT and VAT depots. However, in VAT, GCs induce DNL, higher palmitic acid (PA), macrophage infiltration, and proinflammatory cytokine levels, accompanied by systemic nonesterified fatty acid (NEFA) elevation, hyperinsulinemia, and higher homeostatic model assessment for insulin resistance (HOMA-IR) levels compared with diet-induced obesity. Thus, chronic hypercortisolism induces DNL and fatty acid composition changes toward increased SFA and reduced polyunsaturated fatty acid (PUFA) levels in VAT, promoting macrophage recruitment and proinflammatory cytokines, suggesting a worse cardiometabolic profile even compared with HFD mice.

Loss of p53 Sensitizes Cells to Palmitic Acid-Induced Apoptosis by Reactive Oxygen Species Accumulation.

Palmitic acid, the most common saturated free fatty acid, can lead to lipotoxicity and apoptosis when overloaded in non-fat cells. Palmitic acid accumulation can induce pancreatic β-cell dysfunction and cardiac myocyte apoptosis. Under various cellular stresses, the activation of p53 signaling can lead to cell cycle arrest, DNA repair, senescence, or apoptosis, depending on the severity/type of stress. Nonetheless, the precise role of p53 in lipotoxicity induced by palmitic acid is not clear. Here, our results show that palmitic acid induces p53 activation in a dose- and time-dependent manner. Furthermore, loss of p53 makes cells sensitive to palmitic acid-induced apoptosis. These results were demonstrated in human colon carcinoma cells (HCT116) and primary mouse embryo fibroblasts (MEF) through analysis of DNA fragmentation, flow cytometry, colony formation, and Western blots. In the HCT116 p53−/− cell line, palmitic acid induced greater reactive oxygen species formation compared to the p53+/+ cell line. The reactive oxygen species (ROS) scavengers N-acetyl cysteine (NAC) and reduced glutathione (GSH) partially attenuated apoptosis in the HCT116 p53−/− cell line but had no obvious effect on the p53+/+ cell line. Furthermore, p53 induced the expression of its downstream target genes, p21 and Sesn2, in response to ROS induced by palmitic acid. Loss of p21 also leads to more palmitic acid-induced cell apoptosis in the HCT116 cell line compared with HCT116 p53+/+ and HCT116 p53−/−. In a mouse model of obesity, glucose tolerance test assays showed higher glucose levels in p53−/− mice that received a high fat diet compared to wild type mice that received the same diet. There were no obvious differences between p53−/− and p53+/+ mice that received a regular diet. We conclude that p53 may provide some protection against palmitic acid- induced apoptosis in cells by targeting its downstream genes in response to this stress.

Pig slurry improves the anaerobic digestion of waste cooking oil.

Recycling of waste cooking oil greatly reduces the environmental impact of its disposal. As fats can give rise to high methane yields, the use of waste cooking oil for biogas production seems a promising solution. The aim of this work was to test the anaerobic digestion performances of waste cooking oil in co-digestion with pig slurry, the fat degradation dynamics and the relationships between digestion performances and pig slurry compositional properties. In laboratory batch, static, mesophilic anaerobic conditions, the treatments waste cooking oil in synthetic hydration medium (WCO + HM) and waste cooking oil in pig slurry (WCO + PS) were compared. Pig slurry alone was included for reference. Co-digestion with pig slurry greatly shortened the lag phase (by 58.3%) and increased the overall methane production per reactor (by 15.5%). An increase in emulsion stability of the biphasic system and an earlier triglyceride degradation were associated with the better anaerobic digestion performances in the WCO + PS reactors. A negative, however reversible, effect of palmitic acid accumulation on methane production was also observed. These results are encouraging for the application of co-digestion of waste cooking oil and pig slurry in agricultural biogas plants.

MTORC2 Regulates Lipogenic Gene Expression through PPARγ to Control Lipid Synthesis in Bovine Mammary Epithelial Cells.

The mechanistic target of rapamycin complex 2 (mTORC2) primarily functions as an effector of insulin/PI3K signaling to regulate cell proliferation and is associated with cell metabolism. However, the function of mTORC2 in lipid metabolism is not well understood. In the present study, mTORC2 was inactivated by the ATP-competitive mTOR inhibitor AZD8055 or shRNA targeting RICTOR in primary bovine mammary epithelial cells (pBMECs). MTT assay was performed to examine the effect of AZD8055 on cell proliferation. ELISA assay and GC-MS analysis were used to determine the content of lipid. The mRNA and protein expression levels were investigated by RT/real-time PCR and western blot analysis, respectively. We found that cell proliferation, mTORC2 activation, and lipid secretion were inhibited by AZD8055. RICTOR was knocked down and mTORC2 activation was specifically attenuated by the shRNA. Compared to control cells, the expression of the transcription factor gene PPARG and the lipogenic genes LPIN1, DGAT1, ACACA, and FASN was downregulated in RICTOR silencing cells. As a result, the content of intracellular triacylglycerol (TAG), palmitic acid (PA), docosahexaenoic acid (DHA), and other 16 types of fatty acid was decreased in the treated cells; the accumulation of TAG, PA, and DHA in cell culture medium was also reduced. Overall, mTORC2 plays a critical role in regulating lipogenic gene expression, lipid synthesis, and secretion in pBMECs, and this process probably is through PPARγ. This finding provides a model by which lipogenesis is regulated in pBMECs.

A high-fat diet promotes depression-like behavior in mice by suppressing hypothalamic PKA signaling

Obesity is associated with an increased risk of depression. The aim of the present study was to investigate whether obesity is a causative factor for the development of depression and what is the molecular pathway(s) that link these two disorders. Using lipidomic and transcriptomic methods, we identified a mechanism that links exposure to a high-fat diet (HFD) in mice with alterations in hypothalamic function that lead to depression. Consumption of an HFD selectively induced accumulation of palmitic acid in the hypothalamus, suppressed the 3′, 5′-cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway, and increased the concentration of free fatty acid receptor 1 (FFAR1). Deficiency of phosphodiesterase 4A (PDE4A), an enzyme that degrades cAMP and modulates stimulatory regulative G protein (Gs)-coupled G protein-coupled receptor signaling, protected animals either from genetic- or dietary-induced depression phenotype. These findings suggest that dietary intake of saturated fats disrupts hypothalamic functions by suppressing cAMP/PKA signaling through activation of PDE4A. FFAR1 inhibition and/or an increase of cAMP signaling in the hypothalamus could offer potential therapeutic targets to counteract the effects of dietary or genetically induced obesity on depression.

Polysaccharide from Rubus chingii Hu affords protection against palmitic acid-induced lipotoxicity in human hepatocytes

Palmitic acid (PA) is known to induce lipotoxicity, a metabolic syndrome as a result of lipid accumulation in multiple cell lines. Bioactive phytochemicals derived from vegetables and fruits have gained increasing attention owing to their potential on suppressing the detrimental effect of excessive PA accumulation. However, the protective effect of natural phytochemicals derived from Rubus chingii Hu, a kind of fruit widely grown in China, against PA-induced lipotoxicity is still uncleared. In the present study, we therefore extracted the polysaccharide from Rubus chingii Hu, and identified its chemical structure. Structural characterization by HPLC, HPGPC, IR spectroscopy and GC indicated that the polysaccharide mainly consists of galacturonic acid and arabinose with copious 1 → 2 glycosidic linkages in its backbone. In addition, our results showed the cytoprotective effect of the polysaccharide against PA-induced lipotoxicity in normal human hepatocyte cell line L02. Further study indicated that the polysaccharide mitigated oxidative stress through impeding cellular reactive oxygen species (ROS) accumulation, alleviating mitochondrial membrane potential (MMP) collapse and attenuating glutathione (GSH) reduction. Overall, this study revealed that Rubus chingii Hu polysaccharide was capable of effectively alleviating palmitic acid-induced lipotoxicity, which provided a novel perspective of the health-promoting potential of isolated polysaccharide.