Reduction In Lipid Content Research Articles

Adiponectin Reduces Lipid Content in Chicken Myoblasts by Activating AMPK Signaling Pathway.

Studies in mammals have shown that adiponectin is secreted mainly by adipocytes, and it plays a crucial role in glucose and lipid metabolism in muscles. Clarifying the cross-talk role of adiponectin between adipose tissue and skeletal muscle tissue is very important for internal homeostasis. The glucose and lipid metabolism of chicken is different from that of mammals, and the role of adiponectin in chickens is unclear. Therefore, it is of great significance to study the effect and mechanism of adiponectin on lipid metabolism in chickens. In the present study, the regulating effect of adiponectin on lipid metabolism in chicken myoblasts was explored by adding a certain concentration of exogenous recombinant adiponectin. Results showed that adiponectin reduced intracellular lipid content, increasing the mRNA expression of adiponectin receptor and cellular uptake of glucose and fatty acids. In addition, adiponectin activated the 5′ adenosine monophosphate activated protein kinase (AMPK) signaling pathway. The above results suggested that adiponectin reduced intracellular lipid content, mainly by binding to adiponectin receptor, activating AMPK pathway, increasing cellular uptake of glucose and fatty acids and promoting lipid oxidation.

CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near-Infrared Spectroscopy): A Randomized Trial.

BackgroundThe effect of physical exercise on lipid content of coronary artery plaques is unknown. With near infrared spectroscopy we measured the effect of high intensity interval training (HIIT) on lipid content in coronary plaques in patients with stable coronary artery disease following percutaneous coronary intervention.Methods and ResultsIn CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near‐Infrared Spectroscopy) 60 patients were randomized to 6 months supervised HIIT or to a control group. The primary end point was change in lipid content measured as maximum lipid core burden index at 4 mm (maxLCBI4mm). A predefined cutoff of maxLCBI4mm >100 was required for inclusion in the analysis. Forty‐nine patients (HIIT=20, usual care=29) had maxLCBI4mm >100 at baseline. Change in maxLCBI4mm did not differ between groups (−1.2, 95% CI, −65.8 to 63.4, P=0.97). The estimated reduction in maxLCBI4mm was −47.7 (95% CI, −100.3 to 5.0, P=0.075) and −46.5 (95% CI, −87.5 to −5.4, P=0.027) after HIIT and in controls, respectively. A negative correlation was observed between change in peak oxygen uptake (VO2peak) and change in lipid content (Spearman’s correlation −0.44, P=0.009). With an increase in VO2peak above 1 metabolic equivalent task, maxLCBI4mm was on average reduced by 142 (−8 to −262), whereas the change was −3.2 (154 to −255) with increased VO2peak below 1 metabolic equivalent task.ConclusionsSix months of HIIT following percutaneous coronary intervention did not reduce lipid content in coronary plaques compared with usual care. A moderate negative correlation between increase in VO2peak and change in lipid content generates the hypothesis that exercise with a subsequent increase in fitness may reduce lipid content in coronary atheromatous plaques.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT02494947.

Abstract 521: Parkin Has Non-canonical Roles In Macrophage Lipid Metabolism With Effects On Atherosclerosis

Defects in the E3 ubiquitin ligase Parkin are sine qua non of Parkinson and related neurodegenerative diseases. Loss of ubiquitination of distinct targets leads to accumulation of cytotoxic protein aggregates, loss of mitophagy, and defects in lipid metabolism. Given the critical role of these processes in plaque macrophages, we set out to define the role of Parkin in atherosclerosis. Pro-atherogenic LDLR-KO mice were transplanted with bone marrow (BM) from wild type and Parkin-KO mice and lesion formation stimulated by 4 months of Western diet feeding. Mice transplanted with wild type BM developed lipid-rich atherosclerotic plaques in both the aortic root and whole aorta replete with foam cell macrophages. In contrast, mice transplanted with Parkin-deficient BM had significantly reduced plaque burden with concomitant reductions in lipid content, foam cell macrophages, and surrogates of plaque complexity including reduced lesional apoptosis and necrotic core formation. The paradoxical atherogenic role for Parkin including development of lipid-laden foam cell macrophages led us to focus on the impact of Parkin in macrophage lipid handling. We find that Parkin mediates the ubiquitination and stabilization of scavenger receptor CD36, a key lipid transporter in macrophages. Parkin-null macrophages had reduced expression of CD36 and concomitant reductions in oxLDL uptake. Further, Parkin deficiency decreased cholesterol efflux in macrophages exacerbating macrophage lipid storage. These results suggest that the non-canonical functions of Parkin in lipid metabolism outweigh its traditional cytoprotective roles in macrophages and mediate its deleterious effects on atherosclerotic progression.

Lack of lipid accumulation in two species of chalcidoid wasps with secondarily evolved phytophagy

AbstractStable co‐evolutionary relationships between species may result in the loss of autonomous synthesis of essential nutrients when these can be obtained from the ecological partner. Parasitoid insects obtain most of their nutrients from their host, and many lineages do not increase their adult lipid reserves even when feeding on a surplus of sugars. Several clades within the parasitoid Hymenoptera have lost the parasitoid lifestyle and switched to either a predatory or a phytophagous lifestyle. Here, we test whether adult lipid accumulation is reactivated in two species that independently evolved a phytophagous lifestyle from parasitoid ancestors. The larvae of Megastigmus aculeatus (Swederus) (Hymenoptera: Chalcidoidea: Torymidae) and Bruchophagus platypterus (Walker) (Hymenoptera: Chalcidoidea: Eurytomidae) obligatorily feed on seeds of specific plants. Seeds of wild host plants were collected and the emerging wasps were tested for the lipid accumulation phenotype using whole‐body diethyl ether extraction. Both species had significantly reduced lipid content after 1 week ad libitum access to sugars compared to the lipid content at emergence, indicating a lack or negligible level of lipogenesis. Therefore, the secondary switch to phytophagy was not associated with recovery of lipid accumulation in these species. We discuss these results in relation to the lipid content of the host seeds and the reversibility of the lipid accumulation phenotype. We infer that the close relationship among seed‐feeding insects and their hosts allows the seed‐feeders to rely on a diet with predictable lipid quantities which relaxes the need for autonomous lipid synthesis.

Evaluation of the Acute Effects of Arsenic on Adults of the Neotropical Native Fish Cnesterodon decemmaculatus Using a Set of Biomarkers.

Neotropical fish Cnesterodon decemmaculatus were exposed to different sublethal concentrations (0.5, 1.0 and 5.0 mg As/L) of sodium arsenite (As III) to determine the median lethal concentration (LC50; 96 h) and to evaluate the response of a set of biomarkers (genotoxic, behavioral, biochemical, and metabolic). At the end of the exposure (96 h), fish were video-recorded for behavior assessment. We used the micronucleus and nuclear abnormality tests and the comet assay in peripheral blood as genotoxicity biomarkers. In regard to biochemical and metabolic biomarkers, we dissected the brain for acetylcholinesterase (AChE) activity; the liver for glutathione-S-transferase (GST) and catalase (CAT) activity and glutathione content (GSH); the gills for GSH content; and muscle for AChE, energy metabolism of lipids, carbohydrates, and proteins, and the electron transport system activity of the mitochondrial chain. We calculated an index using metabolic biomarkers, to determine the cellular energy allocation. The LC50 value was 7.32 mg As/L. The As affected some swimming parameters in females. No significant differences in micronucleus were found compared with the control, whereas nuclear aberrations increased significantly at 1.0 and 5.0 mg As/L. The genomic damage index and the percentage of cells with DNA damage (measured by the comet assay) showed a significant increase in the As-treated groups, and this technique was the most sensitive for detecting genotoxic damage. The As affected the antioxidant system (mainly GSH, CAT, and GST) and reduced the lipid content. A preliminary baseline was generated for the response of C. decemmaculatus exposed to sublethal concentrations of As, when it alters swimming behavior and the antioxidant system, has genotoxic effects, and reduces lipid content. Environ Toxicol Chem 2022;41:1246-1259. © 2022 SETAC.

Mitochondrial Transplantation Enhances Phagocytic Function and Decreases Lipid Accumulation in Foam Cell Macrophages.

Macrophages have mechanisms for eliminating cholesterol from cells. If excess cholesterol is not eliminated from the macrophages, then transformation into a foam cell may occur. Foam cells are a hallmark of the atherosclerotic lesions that contribute to the development and rupture of atherosclerotic plaques. Several in vitro and in vivo studies have shown changes in the macrophage phenotype and improved phagocytosis after the acquisition of functional mitochondria. However, the effect of mitochondrial transplantation on promoting phagocytosis and phenotypic changes in lipid-loaded macrophages leading to foam cells has not been studied. We aimed to prove that the transplantation of healthy mitochondria to highly cholesterol-loaded macrophages induces macrophage phagocytosis and reduces the macrophage shift towards foam cells. For this purpose, using a murine macrophage cell line, RAW264.7, we determined if mitochondria transplantation to 7-ketocholesterol (7-KC)-loaded macrophages reduced lipid accumulation and modified their phagocytic function. We evidenced that mitochondrial transplantation to 7-KC-loaded macrophages reestablished phagocytosis and reduced lipid content. In addition, CPT1a expression and anti-inflammatory cytokines were restored after mitochondrial transplantation. We have developed a potential therapeutic approach to restore foam cell functionality.

Oocyte metabolic function, lipid composition, and developmental potential are altered by diet in older mares.

Dietary supplementation is the most feasible method to improve oocyte function and developmental potential in vivo. During three experiments, oocytes were collected from maturing, dominant follicles of older mares to determine whether short-term dietary supplements can alter oocyte metabolic function, lipid composition, and developmental potential. Over approximately 8 weeks, control mares were fed hay (CON) or hay and grain products (COB). Treated mares received supplements designed for equine wellness and gastrointestinal health, flaxseed oil, and a proprietary blend of fatty acid and antioxidant support (reproductive support supplement (RSS)) intended to increase antioxidant activity and lipid oxidation. RSS was modified for individual experiments with additional antioxidants or altered concentrations of n-3 to n-6 fatty acids. Oocytes from mares supplemented with RSS when compared to COB had higher basal oxygen consumption, indicative of higher aerobic metabolism, and proportionately more aerobic to anaerobic metabolism. In the second experiment, oocytes collected from the same mares prior to (CON) and after approximately 8 weeks of RSS supplementation had significantly reduced oocyte lipid abundance. In the final experiment, COB was compared to RSS supplementation, including RSS modified to proportionately reduce n-3 fatty acids and increase n-6 fatty acids. The ability of sperm-injected oocytes to develop into blastocysts was higher for RSS, regardless of fatty acid content, than for COB. We demonstrated that short-term diet supplementation can directly affect oocyte function in older mares, resulting in oocytes with increased metabolic activity, reduced lipid content, and increased developmental potential.

Eukaryotic elongation factor 2 kinase regulates foam cell formation via translation of CD36.

Eukaryotic elongation factor 2kinase (eEF2K) is an atypical protein kinase that controls protein synthesis in cells under stress. Although well studied in cancer, less is known about its roles in chronic inflammatory diseases. Here, we examined its regulation of macrophage cholesterol handling in the context of atherosclerosis. eEF2K mRNA expression and protein activity were upregulated in murine bone marrow-derived macrophages (BMDMs) exposed to oxidized low-density lipoprotein cholesterol (oxLDL). When incubated with oxLDL, BMDMs from eEF2K knockout (Eef2k-/- ) mice formed fewer Oil Red O+ foam cells than Eef2k+/+ BMDMs (12.5%±2.3% vs. 32.3%±2.0%, p<.01). Treatment with a selective eEF2K inhibitor, JAN-384, also decreased foam cell formation for C57BL/6J BMDMs and human monocyte-derived macrophages. Disabling eEF2K selectively decreased protein expression of the CD36 cholesterol uptake receptor, mediated by a reduction in the proportion of translationally active Cd36mRNA. Eef2k-/- mice bred onto the Ldlr-/- background developed aortic sinus atherosclerotic plaques that were 30% smaller than Eef2k+/+ -Ldlr-/- mice after 16weeks of high cholesterol diet (p<.05). Although accompanied by a reduction in plaque CD36+ staining (p<.05) and lower CD36 expression in circulating monocytes (p<.01), this was not associated with reduced lipid content in plaques as measured by oil red O staining. Finally, EEF2K and CD36mRNA levels were higher in blood mononuclear cells from patients with coronary artery disease and recent myocardial infarction compared to healthy controls without coronary artery disease. These results reveal a new role for eEF2K in translationally regulating CD36 expression and foam cell formation in macrophages. Further studies are required to explore therapeutic targeting of eEF2K in atherosclerosis.

Effect of Hempseed Cake (Cannabis sativa L.) Incorporation on the Physicochemical and Antioxidant Properties of Reconstructed Potato Chips.

Hempseed (Cannabis sativa L.) cake is a by-product after cold-pressing of oil from the hempseed, which is rich in protein and fiber. This study investigated the effect of hempseed cake incorporation on the physicochemical and antioxidant properties of reconstructed potato chips. Varying levels of hempseed cake (0, 5%, 10%, 15%, and 20%) were added, and the results showed that the addition of hempseed cake at 20% level significantly increased the protein and total dietary fiber content from 2.74 ± 0.62 g/100 g to 9.66 ± 0.28 g/100 g and from 2.76 ± 0.31 g/100 g to 13.57 ± 0.42 g/100 g, respectively. In addition, a 20% reduction in lipid content was observed in the 20% hempseed cake addition group. Furthermore, lightness value (L*) was significantly reduced from 72.23 ± 1.22 to 46.40 ± 1.76, while the hardness was enhanced with a higher level of hempseed cake supplementation in the potato chips sample. Compared with the control (no hempseed cake), the supplement of 20% cake increased the total phenolic content from 0.19 ± 0.01 to 0.26 ± 0.01 mg GAE/g. The ABTS radical scavenging rate was also significantly enhanced with the increased levels of hemp cake. However, the peroxide value and TBARS results showed that the addition of hempseed cake accelerated the lipid oxidation in the sample, possibly due to the highly unsaturated fatty acid residues in the hempseed cake. The results suggested that more research is needed for the incorporation of hempseed cake in potato chips.

Screening of Plant-Derived Natural Extracts to Identify a Candidate Extract Capable of Enhancing Lipid Synthesis in Keratinocytes.

BackgroundReduced lipid content in the stratum corneum is a major cause of skin-barrier dysfunction in various pathological conditions. Promoting lipid production is a potential strategy to improve skin-barrier function. Recent evidence supports the beneficial effects of adiponectin on lipid metabolism and senescence in keratinocytes.ObjectiveThis study aimed to investigate whether plant extracts can enhance skin-barrier function.MethodsWe screened fruit and herb extracts that enhance the lipid synthesis of keratinocytes via AMP-activated protein kinase (AMPK) activation and SIRT1 signaling in the adiponectin pathway. The levels of major lipid synthesis enzymes and transcription factors as well as epidermal barrier lipids involved in adiponectin-associated epidermal barrier formation were evaluated in the herbal extracts- or adiponectin-treated human epidermal keratinocyte and equivalent models. The mRNA expression of major lipid synthesis enzymes increased following treatment with Lycii Fructus, Prunus tomentosa, and Melia toosendan extracts.ResultsThe expression of transcription factors SIRT1, liver X receptor α, peroxisome proliferator-activated receptors (PPARs), and sterol regulatory element-binding proteins (SREBPs) were upregulated. Levels of free fatty acids, cholesterol, and ceramides were elevated. The expression of keratinocyte differentiation markers increased. In particular, among fruit extracts with a detectable effect, Melia toosendan induced the highest expression of lipid synthase.ConclusionThese results indicate that Melia toosendan is a promising candidate for improving skin-barrier function.

CHEMOSENSITIZING EFFECTS OF GDF11 IN HUMAN HEPATOCELLULAR CARCINOMA CELLS

Hepatocellular carcinoma (HCC) ranks as the second leading cause of cancer death globally; this neoplasm accounts for approximately 90% of liver cancers, and about 850,000 new cases are reported annually. Several factors increase the likelihood of developing HCC, such as excessive alcohol consumption, hepatitis B and C virus infection, metabolic syndrome, and a diet high in lipids and cholesterol. The chronic lesions that the liver can suffer due to the aggression of these factors usually generate lower grade pathologies such as fatty liver, hepatitis, and cirrhosis, which can evolve into HCC. In 2019 Gerardo-Ramirez and collaborators from our group reported the ability of GDF11 to subtract aggressiveness to several HCC-derived cell lines HCC (Huh7, Hep3B, SNU-182, Hepa 1-6 and HepG2); they found that GDF11 reduced proliferation, metastatic capacity, colony, and spheroid formation and invasiveness in those cell lines. Findings by Gerardo-Ramirez et al. (2019) identified transcriptional repression of cyclins D1 and A and overexpression of p27. Additionally, an increase in the expression of epithelial markers E-cadherin and Occludin was observed; conversely, mesenchymal-type features such as N-cadherin and Snail decreased with GDF11 treatment, confirming that this growth factor-induced a mesenchymal to epithelial transition. Furthermore, our group reported the effect of GDF11 in reducing lipid content, especially cholesterol and triglycerides. It was also confirmed that GDF11 reduced mevalonate pathway proteins in Huh7 and Hep3B liver cancer cell lines. Additionally, they reported that GDF11 was able to impair mitochondrial functionality and its structure. Moreover, GDF11 treatment induced an alteration of glycolytic capacity and oxygen consumption rate in these models. To determine the sensitizing effect of GDF11 in the Hep3B cell line. Specific: To determine the capacity of GDF11 in the reduction of the EC50 of cisplatin. We used the HCC cell line Hep3B (ATCC). A 72-h pretreatment with GDF11 or without was performed; then we treated the cells with cisplatin at various concentrations (0, 2.5, 5, 10, 15, 15, 25, 50, and 100 μM), incubated for 48 h, and cell viability assay was performed by crystal violet. In our experiments, GDF11 has shown an increased sensitivity of Hep3B cells to cisplatin treatment by significantly reducing the mean effective dose (EC50) from 22.26 μM to 8.11 μM this result was observed by crystal violet assay and by light microscopy. Results demonstrate that GDF11 has sensitizing effects against cisplatin treatment on the liver tumor cell line Hep3B. This agrees with previous results of our group where a detrimental impact in liver tumor cells is observed by the GDF11 treatment and contrast with other works where TGF-β family members have chemoresistance effects. GDF11 pretreatment sensitizes the HCC cell line Hep3B by reducing the cisplatin EC50. Conacyt Fronteras de la Ciencia 1320 The authors declare that there is no conflict of interest.

The role of exercise intensity on fatty liver in rats.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is often caused by obesity. Currently, moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) are two effective treatments for reducing fat mass in patients with obesity and NAFLD. However, the comparative fat-reducing effects and underlying molecular mechanisms of MICT and HIIT remain unclear. This comprehensive study was performed on male Wistar rats treated with standard diet, high-fat diet, MICT, and HIIT to explore their comparative fat-reducing effects and corresponding molecular mechanisms. HIIT had a greater effect on hepatic vacuolation density and lipid content reduction than MICT, and triglyceride and total cholesterol levels in the serum and the liver demonstrated different sensitivities to different exercise training programs. At the molecular level, both MICT and HIIT altered the processes of fatty acid synthesis, fatty acid transport, fatty acid β-oxidation, and cholesterol synthesis, wherein the transcriptional and translational levels of signaling molecules peroxisome proliferator-activated receptors (PPARs) regulating fatty acid and cholesterol synthesis were strongly changed. Moreover, the metabolic pathways of amino acids, bile acids, and carbohydrates were also affected according to transcriptome analysis, and the changes in the above-mentioned processes in the HIIT group were greater than those in the MICT group. In combination with the search tool for the retrieval of interacting genes/proteins (STRING) analysis and the role of PPARs in lipid metabolism, as well as the expression pattern of PPARs in the MICT and HIIT groups, the MICT-and HIIT-induced fat loss was mediated by the PPAR pathway, causing feedback responses in fatty acid, steroid, amino acid, bile acid, and carbohydrate metabolism, and HIIT had a better fat-reducing effect, which may be initiated by PPAR-α. This study provides a theoretical basis for targeted therapy of patients with obesity and NAFLD.

Myelin and non-myelin debris contribute to foamy macrophage formation after spinal cord injury

Tissue damage after spinal cord injury (SCI) elicits a robust inflammatory cascade that fails to resolve in a timely manner, resulting in impaired wound healing and cellular regeneration. This inflammatory response is partly mediated by infiltrating immune cells, including macrophages. As professional phagocytes, macrophages initially play an important role in debris clearance at the injury site, which would be necessary for proper tissue regeneration. After SCI, most macrophages become filled with lipid droplets due to excessive uptake of lipid debris, assuming a “foamy” phenotype that is associated with a proinflammatory state. Myelin has been assumed to be the main source of lipid that induces foamy macrophage formation after injury given its abundance in the spinal cord. This assumption has led to the widespread use of purified myelin treatment to model foamy macrophage formation in vitro. However, the assumption that myelin is necessary for foamy macrophage formation remains untested. To this end, we developed a novel foamy macrophage assay utilizing total spinal cord homogenate to include all sources of lipid present at the injury site. Using the myelin basic protein knockout (MBP KO, i.e., Shiverer) mice that lack myelin, we investigated lipid accumulation in foamy macrophages. Primary macrophages treated with myelin-deficient spinal cord homogenate still formed large lipid droplets typically observed in foamy macrophages, although to a lesser degree than cells treated with normal homogenate. Similarly, MBP KO mice subjected to contusive spinal cord injury also formed foamy macrophages that exhibited reduced lipid content and associated with improved histological outcomes and reduced immune cell infiltration. Therefore, the absence of myelin does not preclude foamy macrophage formation, indicating that myelin is not the only major source of lipid that contributes this pathology, even though myelin may alter certain aspects of its inflammatory profile.

The use of tunicate (Ciona intestinalis) as a sustainable protein source in fish feed – Effects on the extrusion process, physical pellet quality and microstructure

The aim of this research was to study the effect of the replacement of fishmeal (FM) or soy protein concentrate (SPC) by tunicate meal (Ciona intestinalis) on the extrusion process, physical pellet quality, pellet expansion, and microstructure. The experiment was based on a 3-component simplex-centroid mixture design. Models with R2 in the range of 0.574–0.999 (P = 0.03 to < 0.0001) were established for specific mechanical energy (SME), temperature behind extruder die (Tdie), apparent dough viscosity in the extruder die (Vdie), pellet hardness, durability, expansion, and microstructure parameters. Increase in SME and Tdie were mainly explained by the reduced lipid content in the feed mix due to the replacement of FM with tunicate or SPC. Reduced Vdie was mainly an effect of increased tunicate level and with the lowest value found for the pure tunicate blend. There was an increase in volumetric expansion and open porosity by replacement of SPC with tunicate, explained by this decrease in Vdie. Reduced hardness and durability were found for blends high in SPC due to incomplete plasticisation. Extrudate expansion, fat adsorption capacity and leakage were explained by the extrudate microstructure measured by X-ray microtomography. Within the boundary of the chosen design, 64% of the FM can be replaced by tunicate meal without compromising physical feed quality. Due to its viscosity behaviour, tunicate meal can improve pellet expansion and fat absorption capacity of extruded feed.

Dual use of a local Protosiphon isolate BENHA2020 for biodiesel production and antioxidant activity of lipid-free biomass: A novel biorefinery approach for biomass valorization

The present study aimed to isolate and evaluate a local Protosiphon sp. for biodiesel production and antioxidant activity of its residual lipid-free biomass. Phylogenetic analysis confirmed that the isolate is Protosiphon botryoides. In the control medium using 250 mg L−1 NaNO3 as a nitrogen source, cells showed 37.7 dw% lipid content at stationary phase. At different nitrogen levels, increasing of nitrogen concentration resulted in obvious increase in growth, showing the maximum biomass productivity of 0.133 g L−1 d−1 at middle exponential phase using 750 mg L−1 NaNO3, with simultaneous reduction in lipid content, reaching its lowest recorded value of 27.9 dw%. Due to enhancement of lipid content of N-deficient culture (125 mg L−1 NaNO3), it showed the highest lipid productivity of 41.3 mg L−1 d−1. Fatty acid analysis confirmed the dominance of linoleic acid, eicosatrienoic acid, oleic acid, and palmitic acid. Biodiesel characteristics complied with the international standards and showed better properties than some other reported biodiesel promising microalgae. In addition, lipid-free biomass showed high radical scavenging activity of 55.3%, which confirms its suitability as additional nutritional and pharmaceutical material for enhanced biomass valorization.

Hypoglycemic and hypolipidemic dual activities of extracts and flavonoids from Desmodium caudatum and an efficient synthesis of the most potent 8-prenylquercetin

Since glucolipid metabolism disorders is often the mono-target therapy fails in managing blood glucose and lipid levels and the other complications, it is urgent and necessary to seek for the new potential drugs or functional food acting on multi-targets. The hypoglycemic and hypolipidemic dual activities of the root, stems and leaves of Desmodium caudatum, which is used for traditional Chinese medicine, was evaluated. Twelve extracts with different extraction conditions were prepared and extract 9 was find to exhibit potential inhibitory activities of fructose-1, 6-bisphosphatase (FBPase), α-glucosidase, and pancrelipase, as well as promote cellular glucose consumption and reduce cellular content of lipid. Five flavonoids were isolated and identified from extract 9, among which 8-prenylquercetin exhibited potent α-glucosidase (IC50 = 4.38 μM) and FBPase (IC50 = 3.62 μM) dual inhibitory activity, which were 75-fold higher than acarbose (IC50 = 330.10 μM) and comparable with AMP (IC50 = 2.92 μM). In addition, 8-prenylquercetin was able to promote glucose consumption and reduce lipid content. Besides, an efficient synthesis of the most potent 8-prenylquercetin was developed from inexpensive and commercially available rutin in 21% overall yield by 6 steps, which lay the foundation of preparation sufficient amount for follow-up study.

Viral Infection Drives the Regulation of Feeding Behavior Related Genes in Salmo salar.

The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic–pituitary–adrenocortical axes in stress-induced food intake behavior in fish.

High-Throughput Single-Cell Mass Spectrometry Reveals Abnormal Lipid Metabolism in Pancreatic Ductal Adenocarcinoma.

Even populations of clonal cells are heterogeneous, which requires high‐throughput analysis methods with single‐cell sensitivity. Here, we propose a rapid, label‐free single‐cell analytical method based on active capillary dielectric barrier discharge ionization mass spectrometry, which can analyze multiple metabolites in single cells at a rate of 38 cells/minute. Multiple cell types (HEK‐293T, PANC‐1, CFPAC‐1, H6c7, HeLa and iBAs) were discriminated successfully. We found evidence for abnormal lipid metabolism in pancreatic cancer cells. We also analyzed gene expression in a cancer genome atlas dataset and found that the mRNA level of a critical enzyme of lipid synthesis (ATP citrate lyase, ACLY) was upregulated in human pancreatic ductal adenocarcinoma (PDAC). Moreover, both an ACLY chemical inhibitor and a siRNA approach targeting ACLY could suppress the viability of PDAC cells. A significant reduction in lipid content in treated cells indicates that ACLY could be a potential target for treating pancreatic cancer.

High‐Throughput Single‐Cell Mass Spectrometry Reveals Abnormal Lipid Metabolism in Pancreatic Ductal Adenocarcinoma

AbstractEven populations of clonal cells are heterogeneous, which requires high‐throughput analysis methods with single‐cell sensitivity. Here, we propose a rapid, label‐free single‐cell analytical method based on active capillary dielectric barrier discharge ionization mass spectrometry, which can analyze multiple metabolites in single cells at a rate of 38 cells/minute. Multiple cell types (HEK‐293T, PANC‐1, CFPAC‐1, H6c7, HeLa and iBAs) were discriminated successfully. We found evidence for abnormal lipid metabolism in pancreatic cancer cells. We also analyzed gene expression in a cancer genome atlas dataset and found that the mRNA level of a critical enzyme of lipid synthesis (ATP citrate lyase, ACLY) was upregulated in human pancreatic ductal adenocarcinoma (PDAC). Moreover, both an ACLY chemical inhibitor and a siRNA approach targeting ACLY could suppress the viability of PDAC cells. A significant reduction in lipid content in treated cells indicates that ACLY could be a potential target for treating pancreatic cancer.

Dual-energy three-compartment breast imaging for compositional biomarkers to improve detection of malignant lesions

BackgroundWhile breast imaging such as full-field digital mammography and digital breast tomosynthesis have helped to reduced breast cancer mortality, issues with low specificity exist resulting in unnecessary biopsies. The fundamental information used in diagnostic decisions are primarily based in lesion morphology. We explore a dual-energy compositional breast imaging technique known as three-compartment breast (3CB) to show how the addition of compositional information improves malignancy detection.MethodsWomen who presented with Breast Imaging-Reporting and Data System (BI-RADS) diagnostic categories 4 or 5 and who were scheduled for breast biopsies were consecutively recruited for both standard mammography and 3CB imaging. Computer-aided detection (CAD) software was used to assign a morphology-based prediction of malignancy for all biopsied lesions. Compositional signatures for all lesions were calculated using 3CB imaging and a neural network evaluated CAD predictions with composition to predict a new probability of malignancy. CAD and neural network predictions were compared to the biopsy pathology.ResultsThe addition of 3CB compositional information to CAD improves malignancy predictions resulting in an area under the receiver operating characteristic curve (AUC) of 0.81 (confidence interval (CI) of 0.74–0.88) on a held-out test set, while CAD software alone achieves an AUC of 0.69 (CI 0.60–0.78). We also identify that invasive breast cancers have a unique compositional signature characterized by reduced lipid content and increased water and protein content when compared to surrounding tissues.ConclusionClinically, 3CB may potentially provide increased accuracy in predicting malignancy and a feasible avenue to explore compositional breast imaging biomarkers.