Decrease In Lipid Content Research Articles

The trematode Podocotyle atomon modulates biochemical responses of Gammarus locusta to thermal stress but not its feeding rate or survival

Although parasitism is one of the most common species interactions in nature, the role of parasites in their hosts' thermal tolerance is often neglected. This study examined the ability of the trematode Podocotyle atomon to modulate the feeding and stress response of Gammarus locusta towards temperature. To accomplish this, infected and uninfected females and males of Gammarus locusta were exposed to temperatures (2, 6, 10, 14, 18, 22, 26, 30 °C) for six days. Shredding (change in food biomass) and defecation rates (as complementary measure to shredding rate) were measured as proxies for feeding activity. Lipid and glycogen concentrations (energy reserves), catalase (oxidative stress indicator), and phenoloxidase (an immunological response in invertebrates) were additionally measured. Gammarid survival was optimal at 10 °C as estimated by the linear model and was unaffected by trematode infection. Both temperature and sex influenced the direction of infection effect on phenoloxidase. Infected females presented lower phenoloxidase activity than uninfected females at 14 and 18 °C, while males remained unaffected by infection. Catalase activity increased at warmer temperatures for infected males and uninfected females. Higher activity of this enzyme at colder temperatures occurred only for infected females. Infection decreased lipid content in gammarids by 14 %. Infected males had significantly less glycogen than uninfected, while infected females showed the opposite trend. The largest infection effects were observed for catalase and phenoloxidase activity. An exacerbation of catalase activity in infected males at warmer temperatures might indicate (in the long-term) unsustainable, overwhelming, and perhaps lethal conditions in a warming sea. A decrease in phenoloxidase activity in infected females at warmer temperatures might indicate a reduction in the potential for fighting opportunistic infections. Results highlight the relevance of parasites and host sex in organismal homeostasis and provide useful insights into the organismal stability of a widespread amphipod in a warming sea.

Multiple tachykinins and their receptors characterized in the gastropod mollusk Pacific abalone: Expression, signaling cascades, and potential role in regulating lipid metabolism.

Tachykinin (TK) families, including the first neuropeptide substance P, have been intensively explored in bilaterians. Knowledge of signaling of TK receptors (TKRs) has enabled the comprehension of diverse physiological processes. However, TK signaling systems are largely unknown in Lophotrochozoa. This study identified two TK precursors and two TKR isoforms in the Pacific abalone Haliotis discus hannai (Hdh), and characterized Hdh-TK signaling. Hdh-TK peptides harbored protostomian TK-specific FXGXRamide or unique YXGXRamide motifs at the C-termini. A phylogenetic analysis showed that lophotrochozoan TKRs, including Hdh-TKRs, form a monophyletic group distinct from arthropod TKRs and natalisin receptor groups. Although reporter assays demonstrated that all examined Hdh-TK peptides activate intracellular cAMP accumulation and Ca2+ mobilization in Hdh-TKR-expressing mammalian cells, Hdh-TK peptides with N-terminal aromatic residues and C-terminal FXGXRamide motifs were more active than shorter or less aromatic Hdh-TK peptides with a C-terminal YXGXRamide. In addition, we showed that ligand-stimulated Hdh-TKRs mediate ERK1/2 phosphorylation in HEK293 cells and that ERK1/2 phosphorylation is inhibited by PKA and PKC inhibitors. In three-dimensional in silico Hdh-TKR binding modeling, higher docking scores of Hdh-TK peptides were consistent with the lower EC50 values in the reporter assays. The transcripts for Hdh-TK precursors and Hdh-TKR were highly expressed in the neural ganglia, with lower expression levels in peripheral tissues. When abalone were starved for 3 weeks, Hdh-TK1 transcript levels, but not Hdh-TK2, were increased in the cerebral ganglia (CG), intestine, and hepatopancreas, contrasting with the decreased lipid content and transcript levels of sterol regulatory element-binding protein (SREBP). At 24 h post-injection in vivo, the lower dose of Hdh-TK1 mixture increased SREBP transcript levels in the CG and hepatopancreas and accumulative food consumption of abalone. Higher doses of Hdh-TK1 and Hdh-TK2 mixtures decreased the SREBP levels in the CG. When Hdh-TK2-specific siRNA was injected into abalone, intestinal SREBP levels were significantly increased, whereas administration of both Hdh-TK1 and Hdh-TK2 siRNA led to decreased SREBP expression in the CG. Collectively, our results demonstrate the first TK signaling system in gastropod mollusks and suggest a possible role for TK peptides in regulating lipid metabolism in the neural and peripheral tissues of abalone.

Impact of polycyclic aromatic hydrocarbons on photosynthetic and biochemical functions and its bioremediation by Chlorella vulgaris

Among several pollutants found in the aquatic environment, polycyclic aromatic hydrocarbons (PAHs) can interfere with the normal functioning of the aquatic organisms. The aim of this study was to investigate the application of Chlorella vulgaris for bioremediation of different type of PAHs [2-ring Naphthalene (NAP), 3-ring Anthracene (ANT), and 4-ring Pyrene (PYR)] and their impact on photosynthesis and growth of C. vulgaris. After 7 days of exposure of PAHs, growth of C. vulgaris was affected in the order PYR > ANT > NAP. With regard to biomolecules, all PAHs treatments showed a significant decrease in lipid content, but the toxic effect of PYR was more pronounced. Chl a fluorescence study of algal samples indicated that photosystem II (PSII) performance was unaffected by NAP and ANT toxicity, however, severe disruption of PSII activity by PYR was noted. Interestingly, C. vulgaris was able to remove all three PAHs from the media (~90–92 % NAP, ~90–94 % ANT and ~76 % PYR) within 7 days. After 3 days of cultivation, activity of dehydrogenase was increased in NAP and ANT inoculated culture, reflecting metabolization of these compounds which reduced after 7 days. As compared to control culture (no PAHs) a sharp decline in dehydrogenase activity was noted in PYR treated culture (after 3 and 7 days). Based on the results obtained, C. vulgaris could absorb NAP and ANT (linear PAHs) more efficiently than PYR (angular PAH). These results imply that ability of C. vulgaris to degrade PAHs depends in part on the configuration of the ring structure.

Clinical and morphophysiological hepatic alterations caused by the ingestion of food with added ricinoleic acid esters a bioactive with acaricidal potential

The present study investigated the effects of castor oil ricinoleic acid through analysis of blood biochemical parameters and the liver morphology of female rabbits (animal model). The results of Bioassay 1 and Bioassay 2 showed that the reference indexes of the hepatic enzymes alkaline phosphatase, gamma-glutamyl transferase, and alanine aminotransferase were not significantly altered. However, the hepatic enzyme aspartate aminotransferase of the rabbits tested in Bioassay 2 presented alterations, suggesting a hepatotoxic effect of the esters. The morphological and histological data showed that the liver of the rabbits fed with the ester-added food presented the following alterations: a) disorganization of the hepatic cords; b) an increase in intercellular spaces; c) hepatocytes with barely evident cell limits; and d) hepatocytes with irregular and pyknotic nuclei, in most cases displaced to the periphery of the cell due to extensive vacuolation. The histochemical analysis showed that the hepatocytes of the rabbits fed with commercial food with added esters had a decrease in lipid content and an increase in the levels of stored cytoplasmic glycogen.

Predators minimize energy costs, rather than maximize energy gains under warming: Evidence from a microcosm feeding experiment

Abstract Climate warming may alter predator–prey interactions and predator feeding behaviour due to increased metabolic demands. How predators meet these increased demands may depend on trade‐offs in prey energy content and body size, handling time and other functional constraints. We tested hypotheses associated with these trade‐offs with the predatory mite Stratiolaelaps scimitus, and three prey that differed in body size, energy content, and defenses (Folsomia candida, Oppia nitens, and Carpoglyphus lactis). We estimated metabolic rate, predation in choice and no choice feeding trials, movement rate, and lipid and protein content for all four species at 16°C and 24°C. We used these data to estimate the predator's energy demands and compared these to estimated energy intake in the choice feeding trials. Predators had greater metabolic demands at 24°C than at 16°C, but temperature did not affect predator or prey movement rates. Warming decreased lipid content, but not protein content, of all three prey species, leading to lower energy content for C. lactis and O. nitens, but not F. candida. In both feeding trials at 24°C, predators increased their feeding on the smaller, energy‐poor C. lactis, but not the larger, energy‐rich F. candida, resulting in lower estimated energy intake. S. scimitus did not feed on O. nitens at either temperature. Predators increasingly fed on small‐bodied prey under warming and not the large‐bodied prey despite the potential for greater energetic gains from larger prey. We posit that predators minimized energy lost during feeding through lower handling costs associated with C. lactis, rather than maximize energy gain. We conclude that selection of prey based on body size changes with temperature as a trade‐off for predators to balance increased metabolic demands. As predators provide top‐down control and regulate energy flow through the consumption of their prey, changes to predator feeding behaviour with climate warming may affect food web dynamics and ecosystem‐level processes. Read the free Plain Language Summary for this article on the Journal blog.

Structural and Functional Analysis of SHP Promoter and Its Transcriptional Response to FXR in Zn-Induced Changes to Lipid Metabolism.

Zinc alleviates hepatic lipid deposition, but the transcriptional regulatory mechanisms are still unclear. In this study, we characterized the promoter of an SHP (short heterodimer partner) in a teleost Pelteobagrus fulvidraco. The binding sites of an FXR (farnesoid X receptor) were predicted by the SHP promoter, indicating that the FXR mediated its transcriptional activity. The site mutagenesis and the EMSA (electrophoretic mobility shift assay) found that the −375/−384 bp FXR site on the SHP promoter was the functional binding locus responsible for the Zn-induced transcriptional activation. A further study of yellow catfish hepatocytes suggested that the activation of the FXR/SHP is responsible for the effect of Zn on the decreasing lipid content. Thus, this study provides direct evidence of the interaction between the FXR and SHP promoter in fish, and accordingly elucidates the potential transcriptional mechanism by which Zn reduces hepatic lipid accumulation.

Abstract 241: Nicotinamide Nucleotide Transhydrogenase Regulates Mitochondrial Function And Oxldl Induced Macrophage Endothelial Interaction.

Atherosclerosis is a chronic inflammatory disease effecting large and medium sized arteries that leads to the buildup of plaque that contributes to myocardial infraction, stroke, and other pathologies. Mounting evidence has identified mitochondrial reactive oxygen species (ROS) as a key contributor to plaque formation and progression. A inner mitochondrial membrane enzyme Nicotinamide nucleotide transhydrogenase (NNT) sustains NADPH pools required for the mitochondrial antioxidant systems. We have observed that the expression of NNT is decreased in severe human atherosclerotic plaques leading us to hypothesize that the loss of NNT contributes to increased mitochondrial ROS and drives the progression of atherosclerosis by enhancing endothelial and vascular dysfunction. Utilizing AAV/PCSK9 and HFD induced models of early and late-stage atherosclerosis, we found that NNT knockout (NNT KO) mice display significantly increased VCAM-1 expression in aortic endothelial cells during early atherosclerosis and significantly larger necrotic cores in late-stage atherosclerosis. Additionally, NNT KO mice displayed a significantly thinner fibrous cap in late-stage plaques. Similar results were observed in vitro where the loss of NNT in human aortic endothelial cells exacerbated oxLDL induced VCAM-1 expression that was associated with decreased mitochondrial NADPH levels, glutathione peroxidase (Gpx2) activity, and increased H 2 O 2 production. The observed increase in necrotic core area in NNT KO mice is suggestive of increased inflammatory cell recruitment to the plaque. Furthermore, bone marrow derived macrophages (BMDM) from NNT KO mice display decreased lipid content, poor lipid uptake and a predisposition to differentiate into a proinflammatory M1 phenotype. Based on these studies, we conclude that the loss of NNT contributes to unstable plaques with large necrotic cores, mitochondrial ROS driven endothelial dysfunction, increased inflammatory cell recruitment, and enhanced M1 macrophage activity. The novel relationship between vascular NNT expression and plaque severity in human samples implicates NNT as a novel clinical target in atherosclerosis.

Effect of partial fat replacement by hazelnut oil microcapsules in beef burger formulations on physicochemical properties, fatty acid composition, and sensory attributes

This study was conducted to evaluate the effects of partial use of hazelnut oil microcapsules (HOM) instead of animal fat on beef burgers. For this purpose, the burgers were prepared with the replacement levels of 10%, 25%, and 50% of animal fat by HOM. The incorporation of HOM decreased lipid content (from 13.42% to 9.23%) in the burgers. Lipid reformulation improved the fatty acid profiles. The saturated fatty acid content, atherogenic index, and thrombogenic index of burgers decreased from 43.11% to 29.69%, 0.59 to 0.33, and 1.26 to 0.73, respectively. The replacement level of 50% resulted in the lowest thiobarbituric acid reactive substances value. No changes were measured for hardness and gumminess up to the replacement level of 25%. According to these findings, the use of HOM as an animal fat substitute can enhance the nutritional and cooking characteristics and fatty acid profiles of the burgers without affecting sensory acceptability. Novelty impact statement Hazelnut oil microcapsules (HOM) were used for the first time as a fat substitute in burgers. The use of HOM improved the fatty acid profiles and decreased the lipid oxidation of burgers. Consequently, fat replacement with HOM could be an alternative approach to reduce fat content and manipulate the fatty acid profile of the burgers.

Post-mortem histopathology of pituitary and adrenals of COVID-19 patients

BackgroundKnowledge of the exact organ manifestation is essential for a comprehensive understanding of COVID-19 infection. Here, the histopathological changes in the pituitary and adrenal glands were analyzed. MethodsIn this series, the formalin-fixed tissues of 63 pituitary glands and 50 adrenal glands were examined. We performed HE and PAS staining and examined COVID-19 nucleocapsid antibody immunohistochemically in the pituitary glands and adrenals. ResultsHistologically, there was no evidence of COVID-19-specific changes in the pituitary and adrenal glands. Large pituitary necrosis may be interpreted as a shock reaction. Independent of infection, we found one T-cell lymphoma, two adenomas, and four Rathke-type cysts in the pituitary glands, and 70% of the adrenal glands showed decreased lipid content and an increase in compact cells as a stress response. In addition, a cortical adenoma in one adrenal gland and small cortical nodules in three adrenal glands were detected independently of COVID-19. ConclusionPituitary and adrenal glands do not appear histologically predominant in the course of COVID-19.

Mitochondrial-bound hexokinase 1 can affect the glucolipid metabolism and reactive oxygen species production in goose fatty liver

To investigate the functions of hexokinase 1 (HK1) in the formation of goose fatty liver, a total of 40 healthy 63-day-old male Landes geese were selected and randomly assigned to a control group and an overfeeding treatment. In addition, the overexpression or RNA interference assay of HK1, and transcriptome analysis after HK1 overexpression were performed in the goose primary hepatocytes. Data showed that the mRNA expression of hepatic HK1 was upregulated in overfed treatment compared to control on the 19 days of overfeeding. The expression of HK1 was increased in 50 mM glucose treatment in hepatocytes. Moreover, overexpression of HK1 tended to increase the relative lipid accumulation level and had weakened fluorescence intensity of reactive oxygen species (ROS), while knockdown of HK1 resulted in a tendency of relative lipid content decrease and had enhanced fluorescence intensity of ROS in cells in comparison to the control. The verification of transcriptome analysis indicated that the expression of ceruloplasmin (CP), acyl-CoA dehydrogenase medium-chain (ACADM), phosphoglucomutase 2 (PGM2), and phospholipase A2 group IVA (PLA2G4A) was significantly induced by HK1 overexpression, while that of enoyl-CoA hydratase, short chain 1 (ECHS1), cytochrome P450 family 2 subfamily C member 19 (CYP2C19), carnitine palmitoyltransferase 1 A (CPT1A), and oxidative stress-induced growth inhibitor 1 (OSGIN1) was inhibited. In summary, HK1 could promote fat deposition by affecting the process of glucolipid metabolism in the formation of goose fatty liver. Additionally, HK1 might decrease the ROS level in hepatocytes by regulating the expression of redox-related genes. HIGHLIGHTS The HK1 gene may promote the goose fatty liver production. The HK1 gene may be used as a research target to decrease the reactive oxygen species level in fatty liver.

Commentary: Cryotherapy and the sebaceous glands.

Sebaceous glands are exocrine epithelial glands secreting protective surface lipids via a holocrine mechanism in which the sebocytes undergo a programmed disintegration. Sebaceous glands are found in the eyelids as the tarsal meibomian glands and the glands of Zeis near eyelash hair follicles.[1] Pathologically, the ophthalmic sebaceous gland lesions range from benign cysts and chalazia to malignant sebaceous gland carcinoma (SGC), which happens to be the most common eyelid malignancy in the Indian population.[2] Cryotherapy has been extensively used in ophthalmology, dermatology, and surgical specialties as a primary or adjunctive treatment for lesions ranging from intraocular tumors, eyelid cysts, skin tags, warts, and acne vulgaris to cervical and hepatic cancers.[3] There are two mechanisms of cryotherapy: (a) freezing-related direct cellular injury and (b) vascular disruption of the lesion. Its role in the treatment of localized basal cell carcinomas of the eyelid has been documented in the literature with a low recurrence rate.[2] The prolonged healing time with secondary intention healing and depigmentation remains a concern with cryotherapy of the skin tumors. However, it helps in preserving the functionality of essential structures like eyelids and the surrounding lacrimal system. The in vivo biological effect of cryotherapy on normal sebaceous glands has been evaluated with the help of coherent anti-Stokes Raman scattering microscopy by Jung et al.[4] They demonstrated that the effect of lipid crystallization had a limited role in causing cellular disruption. Instead, sebocyte loss occurred at temperatures lower than those required for lipid crystallization. In addition, the cryo-treated sebaceous glands began recovering 1–2 weeks after treatment. Ray Jalian et al.[5] also investigated the role of controlled local skin cooling in causing preferential injury to sebaceous glands to understand its mechanism in treating acne vulgaris. They observed that cooling-induced damage led to a 20% reduction in sebum output for 2 weeks, with minimal collateral injury to surrounding tissues. A higher number of freeze–thaw cycles and slower thawing resulted in more significant tissue injury. Immunohistochemistry-based expression of Ki67 (a proliferative marker) and keratin 15 (a progenitor basal cell marker) was not disrupted by cooling. This led them to conclude that cooling-induced damage was temporary and occurred due to disruption of cellular architecture, enzymatic activity, and decreased lipid content. The sebum output recovered after 4 weeks. Though both these studies used a temperature higher than what is used in ophthalmic practice, they did conclusively demonstrate the limited level of cytotoxicity as well as the temporary duration of the effect of cryotherapy on sebaceous glands. The ophthalmic literature describes the use of cryotherapy as an adjunct in addressing the pagetoid spread seen in eyelid SGC.[6] Lisman (1989) first reported the use of cryotherapy to manage the map biopsy-proven sites of pagetoid spread in six cases of sebaceous gland carcinoma, thereby avoiding exenteration.[7] Shields et al.[6] advocated the application of triple freeze cryotherapy on conjunctival edges to eliminate residual tumor cells. On the contrary, Esmaeli et al.[8] reported satisfactory outcomes in 50 patients of SGC without the need for cryotherapy. A survey of practice patterns in Nordic countries revealed that only 27% of respondents offered cryotherapy as an adjunctive treatment for addressing the pagetoid spread in SGC.[9] Thus, the biological effect of cryotherapy on sebaceous glands is limited and reversible. The reassurance provided by triple freeze and slow thaw to the margins may not be reliable in clinical practice. This fact has been highlighted by Alam et al.[10] in the present issue of this journal. They performed a histopathological study on a portion of excised SGC tumor that was subjected to cryotherapy. Greater than 50% of viable tumor cells along with extensive areas of necrosis were observed on microscopy, and the authors concluded that the cell damage induced by cryotherapy is insufficient for achieving adequate tumor control. We believe that an early diagnosis and timely treatment using a wide (~3-mm margin) full-thickness excision, intraoperative frozen section control, and map biopsy for pagetoid spread remains the preferred practice pattern. The adjunctive use of cryotherapy remains doubtful in the SGC of eyelids. Close monitoring and regular follow-up to observe for recurrences are vital in the long-term management of patients.

Molecular mechanism of benzo [a] pyrene regulating lipid metabolism via aryl hydrocarbon receptor

BackgroundBenzo [a] pyrene (BaP), a potent carcinogen, has been proved that it has toxicological effects via activation the aryl hydrocarbon receptor (AhR) pathway. AhR can participate in regulating lipogenesis and lipolysis. This topic will verify whether BaP regulates lipid metabolism via AhR.Methods(1) C57BL/6 mice were gavaged with BaP for 12 weeks to detect serum lipids, glucose tolerance, and insulin resistance. Morphological changes in white adipose tissue (WAT) were detected by Hematoxylin and Eosin staining. The mRNA expression levels of adipogenesis-related factors included recombinant human CCAAT/enhancer binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid binding protein 4 (FABP4) and inflammatory factors included nuclear factor kappa-B (NF-κB), monocyte chemotactic protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were detected using PCR. (2) Neutral lipid content changes in differentiated 3 T3-L1 adipocytes treated with BaP with and w/o AhR inhibitor were detected by Oil red staining. The protein expression levels of adipogenesis- and decomposition-related factors included PPARγ coactivator-1 alpha (PGC-1α), and peroxisome proliferation-activated receptor alpha (PPARα) were detected using western blotting. The mRNA expression levels of inflammatory factors were detected using PCR.Results(1) BaP inhibited body weight gain, decreased lipid content, increased lipid levels, and decreased glucose tolerance and insulin tolerance in mice; (2) BaP reduced the expressions of C/EBPα, PPARγ, FABP4, PGC-1α, and PPARα and increased the expressions of NF-κB, MCP-1, and TNF-α by activating AhR.ConclusionBaP inhibit fat synthesis and oxidation while inducing inflammation by activating AhR, leading to WAT dysfunction and causing metabolic complications.

Smilax china Polyphenols Stimulate Browning via [Formula: see text]3-Adrenergic Receptor/AMP-Activated Protein Kinase [Formula: see text] Signaling Pathway in 3T3-L1 Adipocytes.

The aim of this study is to investigate the molecular mechanism of Smilax china L. polyphenols (SCLPs) in enhancing lipid metabolism and stimulating browning to reduce lipid accumulation in 3T3-L1 adipocytes. SCLP treatment obviously decreased lipid content in a dose-dependent manner (10-40 μg/mL) in adipocytes. SCLP treatment cooperated with noradrenalin to increase lipolysis. SCLPs reduced the gene expressions of C/EBP[Formula: see text] and Ap2 and enhanced the expressions of ACO, CPT, pHSL/HSL, ATGL, and PKA in adipocytes. Furthermore, SCLPs increased mRNA and protein expressions of brown adipocyte-specific factors (UCP-1, PRDM16, PGC-1α, and PPARγ) and mRNA expressions of beige adipocyte-specific markers (CD137, Tbx1, and Tmem26) in 3T3-L1 adipocytes, as well as mitochondrial biogenesis genes (Nrf1 and Tfam). In addition, according to the immunofluorescence staining, the mitochondria number was increased by SCLP. Moreover, β3-AR or AMPK agonist synergistic SCLPs enhanced the expressions of UCP-1, PRDM16, and PGC-1α. While β3-AR or AMPK antagonist significantly decreased the expressions of these brown adipocyte-specific factors, SCLP treatment inhibited the effect of antagonist to improve the expression of UCP-1, PRDM16, and PGC-1α. These results indicated that SCLPs may regulate lipid metabolism and stimulate browning via the β3-AR/AMPKα signaling pathway. Thus, SCLPs likely have potential therapeutic effects on obesity.

Autophagy enhanced by curcumin ameliorates inflammation in atherogenesis via the TFEB–P300–BRD4 axis

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)–P300–bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid–liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

TAMI-37. STEAROYL-COA DESATURASE 1 IS ESSENTIAL FOR THE GROWTH OF IDH MUTANT GLIOMA

Abstract BACKGROUND Increased de novo lipogenesis is a hallmark of cancer metabolism. In this study, we interrogated the role of de novo lipogenesis in IDH1 mutated glioma’s growth and identified the key enzyme, Stearoyl-CoA desaturase 1 (SCD1) that provides this growth advantage. MATERIALS ANDMETHODS We prepared genetically engineered glioma cell lines (U251 wild-type: U251WT and U251 IDHR132H mutant: U251RH) and normal human astrocytes (empty vector induced-NHA: NHAEV and IDHR132H mutant: NHARH). Lipid metabolic analysis was conducted by using LC-MS and Raman imaging microscopy. SCD1 expression was investigated by The Cancer Genome Atlas (TCGA) data analysis and Western-blotting method. Knock-out of SCD1 was conducted by using CRISPR/Cas9 and shRNA. RESULTS Previously, we showed that IDH1 mut glioma cells have increased monounsaturated fatty acids (MUFAs). TCGA data revealed IDH mut glioma shows significantly higher SCD1 mRNA expression than wild-type glioma. Our model systems of IDH1 mut (U251RH, NHARH) showed increased expression of this enzyme compared with their wild-type counterpart. Moreover, addition of D-2HG to U251WT increased SCD1 expression. Herein, we showed that inhibition of SCD1 with CAY10566 decreased relative cell number and sphere forming capacity in a dose-dependent manner. Furthermore, addition of MUFAs were able to rescue the SCD1 inhibitor induced-cell death and sphere forming capacity. Knock out of SCD1 revealed decreased cell proliferation and sphere forming ability. Decreasing lipid content from the media did not alter the growth of these cells, suggesting that glioma cells rely on de novo lipid synthesis rather than scavenging them from the microenvironment. CONCLUSION Overexpression of IDH mutant gene altered lipid composition in U251 cells to enrich MUFA levels and we confirmed that D-2HG caused SCD1 upregulation in U251WT. We demonstrated the glioma cell growth requires SCD1 expression and the results of the present study may provide novel insights into the role of SCD1 in IDH mut gliomas growth.

Complement Inhibition Targeted to Injury Specific Neoepitopes Attenuates Atherogenesis in Mice.

Rationale: Previous studies have indicated an important role for complement in atherosclerosis, a lipid-driven chronic inflammatory disease associated to oxidative stress in the vessel wall. However, it remains unclear how complement is activated in the process of atherogenesis. An accepted general model for complement activation in the context of ischemia reperfusion injury is that ischemia induces the exposure of neoepitopes that are recognized by natural self-reactive IgM antibodies, and that in turn activate complement.Objective: We investigated whether a similar phenomenon may be involved in the pathogenesis of atherosclerosis, and whether interfering with this activation event, together with inhibition of subsequent amplification of the cascade at the C3 activation step, can provide protection against atherogenesis.Methods and Results: We utilized C2scFv-Crry, a novel construct consisting of a single chain antibody (scFv) linked to Crry, a complement inhibitor that functions at C3 activation. The scFv moiety was derived from C2 IgM mAb that specifically recognizes phospholipid neoepitopes known to be expressed after ischemia. C2scFv-Crry targeted to the atherosclerotic plaque of Apoe−/− mice, demonstrating expression of the C2 neoepitope. C2scFv-Crry administered twice per week significantly attenuated atherosclerotic plaque in the aorta and aortic root of Apoe−/− mice fed with a high-fat diet (HFD) for either 2 or 4 months, and treatment reduced C3 deposition and membrane attack complex formation as compared to vehicle treated mice. C2scFv-Crry also inhibited the uptake of oxidized low-density-lipoprotein (oxLDL) by peritoneal macrophages, which has been shown to play a role in pathogenesis, and C2scFv-Crry-treated mice had decreased lipid content in the lesion with reduced oxLDL levels in serum compared to vehicle-treated mice. Furthermore, C2scFv-Crry reduced the deposition of endogenous total IgM in the plaque, although it did not alter serum IgM levels, further indicating a role for natural IgM in initiating complement activation.Conclusion: Neoepitope targeted complement inhibitors represent a novel therapeutic approach for atherosclerosis.

Rheological and thermal properties of oat flours and starch affected by oat lipids

Understanding how oat lipids affect the functional properties of oat flour and starch is of great importance for development of oat product. In this work, rheological and thermal properties of oat flours and starch affected by oat lipids were investigated. The peak viscosity of oat flour and starch increased as lipid content decreased. Dynamic rheological measurements showed that the storage modulus of oat flour increased, whereas that of oat starch decreased as the lipid content decreased. The gel strength of oat flour and starch increased with decreasing in lipid content. Differential scanning calorimetry results suggested that any decrease in non-starch lipid content had little influence on the properties and the formation of amylose-lipid complexes in oat flour and starch during gelatinization and retrogradation. The removal of non-starch lipids from oats increased the peak viscosity and retrogradation behavior of oat flour and starch.

Meat Quality of Nellore Young Bulls-Effects of Different Days on Feed and Zilpaterol Hydrochloride Supplementation.

Simple Summaryβ-adrenergic agonists have been widely used to improve meat production efficiency and can be a valuable tool for increasing world meat supply. They act as nutrient repartitioning agents, increasing lean tissue deposition but negatively affecting meat quality, notably reducing palatability. While this metabolic modifier improves the growth performance of Zebu breeds, they can impair even more meat quality in feedlot-finished cattle. This study was developed to evaluate the impact of zilpaterol hydrochloride (ZH) feeding duration and time on feed (90 or 117 days), on meat quality, and on composition properties of meat from young Zebu bulls. Supplementing ZH resulted in a leaner and less tender and juicy meat compared to non-supplemented animals, with few differences in fatty acid composition. Feeding animals for 90 or 117 days had a small impact on meat quality attributes. Feeding ZH to Zebu bulls would require additional tenderization practices to reduce the negative effects of ZH on meat quality.Ninety-six Nellore young bulls were fed (90 or 117 day) diets containing ZH (8.33 mg/kg) for 0, 20, 30, or 40 days to evaluate the effects of days on feed (DOF) and length of zilpaterol hydrochloride (ZH) supplementation on meat quality. At the end of feeding period, animals were slaughtered, and samples of the Longissimus muscle were collected to evaluate the chemical composition, fatty acid profile, color stability, shear force, and sensory profile. DOF did not affect chemical composition, shear force, sensory tenderness, and most of fatty acids; however, animals fed for 90 d had lower redness (p < 0.01), sustained juiciness (p < 0.01), and more flavor (p = 0.03) than those fed for 117 d. The ZH supplementation decreased lipid content and redness (p < 0.01), initial and sustained tenderness (p < 0.01), initial and sustained juiciness (p < 0.01), but increased protein (p < 0.01) and shear force (p < 0.01) as compared to non-supplemented animals. The ZH supplementation increased total PUFA, c9,c12-18:2, and 20:4-n6, and decreased c9-20:1 (p < 0.05). Feeding ZH impairs meat quality attributes of Nellore young bulls, regardless of duration of supplementation, while DOF has a small effect on meat quality properties.

Loss of the redox mitochondrial protein mitoNEET leads to mitochondrial dysfunction in B-cell acute lymphoblastic leukemia

B-cell acute lymphoblastic leukemia (ALL) affects both pediatric and adult patients. Chemotherapy resistant tumor cells that contribute to minimal residual disease (MRD) underlie relapse and poor clinical outcomes in a sub-set of patients. Targeting mitochondrial oxidative phosphorylation (OXPHOS) in the treatment of refractory leukemic cells is a potential novel approach to sensitizing tumor cells to existing standard of care therapeutic agents. In the current study, we have expanded our previous investigation of the mitoNEET ligand NL-1 in the treatment of ALL to interrogate the functional role of the mitochondrial outer membrane protein mitoNEET in B-cell ALL. Knockout (KO) of mitoNEET (gene: CISD1) in REH leukemic cells led to changes in mitochondrial ultra-structure and function. REH cells have significantly reduced OXPHOS capacity in the KO cells coincident with reduction in electron flow and increased reactive oxygen species. In addition, we found a decrease in lipid content in KO cells, as compared to the vector control cells was observed. Lastly, the KO of mitoNEET was associated with decreased proliferation as compared to control cells when exposed to the standard of care agent cytarabine (Ara-C). Taken together, these observations suggest that mitoNEET is essential for optimal function of mitochondria in B-cell ALL and may represent a novel anti-leukemic drug target for treatment of minimal residual disease.

Sequencing, Expression, and Functional Analyses of Four Genes Related to Fatty Acid Biosynthesis During the Diapause Process in the Female Ladybird, Coccinella septempunctata L.

The ladybird Coccinella septempunctata L., a predatory insect, serves as an excellent biological control agent against common agricultural pests. It undergoes a diapause phenomenon, during which a large amount of fat accumulates in the abdomen. A comprehensive analysis of this lipid accumulation can reveal the molecular mechanisms underlying diapause regulation, which can be exploited to improve the shipping and transport of the insect for agricultural applications. In this study, we compared the transcriptome of C. septempunctata during non-diapause, diapause, and post-diapause and screened four key genes related to lipid metabolism. The cDNA of these four relevant enzymes, acetyl-CoA carboxylase (ACC), long-chain fatty acid-CoA ligase (ACSL), elongase of very-long-chain fatty acids (ELO), and very-long-chain 3-oxoacyl-CoA reductase (KAR), were cloned using reverse transcription-polymerase chain reaction and rapid amplification of cDNA ends. Their expression profiles were analyzed during the preparation and maintenance phases of diapause and the post-diapause phase. The functions of these four key enzymes in diapause were further verified using RNA interference. All four genes were most closely related to the homeotic gene from Tribolium castaneum. The expression profiles of these four genes were significantly affected under diapause-inducing conditions; their expression level was the highest in the diapause preparation phase, and it gradually decreased with the diapause induction time. RNA interference showed that the target genes play important roles in fat storage during early diapause, and the decrease in their expression leads to a decrease in lipid content in C. septempunctata. These results indicate an important role of ACC, ACSL, ELO, and KAR in lipid accumulation. Our findings could help elucidate the production and accumulation of lipids by insects during the preparation for diapause and improve biological control.