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https://www.readbyqxmd.com/read/29777831/microcystis-bloom-containing-microcystin-lr-induces-type-2-diabetes-mellitus
#1
Qiong Zhang, Wendi Qin, Liuyan Yang, Jing An, Xuxiang Zhang, Hao Hong, Lizhi Xu, Yaping Wang
Epidemiological data from Lake Taihu showed significantly higher incidences of type 2 diabetes mellitus (T2DM) than in other areas of China. This may be related to the occurrence of a Microcystis bloom in Lake Taihu in the summer and autumn every year. The objective of this study is to investigate whether the contaminated water from the Microcystis bloom and the derivative pollutant microcystin-LR (MC-LR) can explain the higher incidences of T2DM. Healthy male mice were fed with water from different regions of Lake Taihu, and were either acutely or chronically exposed to MC-LR through oral administration or intraperitoneal injection...
May 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29775891/protective-effect-of-atorvastatin-meditated-by-hmgcr-gene-on-diabetic-rats-with-atherosclerosis-an-in-vivo-and-in-vitro-study
#2
Yong-Zhi Wang, Lei Yang, Chuan-Fang Li
BACKGROUND: Accelerated atherosclerosis in patients suffering from diabetes represents a major cause of morbidity and mortality. The aim of present study was to investigate the protective effects conferred by atorvastatin (AVT) meditated by the HMGCR gene in diabetic rats with atherosclerosis. METHODS: Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), fasting blood glucose (FBG) and serum insulin (INS) were all determined by means of in vivo experiments...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29751678/-epigallocatechin-3-gallate-synthetic-analogues-inhibit-fatty-acid-synthase-and-show-anticancer-activity-in-triple-negative-breast-cancer
#3
Joan Crous-Masó, Sònia Palomeras, Joana Relat, Cristina Camó, Úrsula Martínez-Garza, Marta Planas, Lidia Feliu, Teresa Puig
(-)-Epigallocatechin 3-gallate (EGCG) is a natural polyphenol from green tea with reported anticancer activity and capacity to inhibit the lipogenic enzyme fatty acid synthase (FASN), which is overexpressed in several human carcinomas. To improve the pharmacological profile of EGCG, we previously developed a family of EGCG derivatives and the lead compounds G28, G37 and G56 were characterized in HER2-positive breast cancer cells overexpressing FASN. Here, diesters G28, G37 and G56 and two G28 derivatives, monoesters M1 and M2, were synthesized and assessed in vitro for their cytotoxic, FASN inhibition and apoptotic activities in MDA-MB-231 triple-negative breast cancer (TNBC) cells...
May 11, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29751019/nighttime-light-exposure-enhances-rev-erb%C3%AE-targeting-micrornas-and-contributes-to-hepatic-steatosis
#4
Patricia C Borck, Thiago M Batista, Jean F Vettorazzi, Gabriela M Soares, Camila Lubaczeuski, Dongyin Guan, Antonio C Boschero, Elaine Vieira, Mitchell A Lazar, Everardo M Carneiro
OBJECTIVE: The exposure to artificial light at night (ALAN) disrupts the biological rhythms and has been associated with the development of metabolic syndrome. MicroRNAs (miRNAs) display a critical role in fine-tuning the circadian system and energy metabolism. In this study, we aimed to assess whether altered miRNAs expression in the liver underlies metabolic disorders caused by disrupted biological rhythms. RESULTS: We found that C3H/HePas mice exposed to ALAN developed obesity, and hepatic steatosis, which was paralleled by decreased expression of Rev-erbα and up-regulation of its lipogenic targets ACL and FAS in liver...
May 8, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29746884/inhibition-of-cellular-fatty-acid-synthase-impairs-replication-of-budded-virions-of-autographa-californica-multiple-nucleopolyhedrovirus-in-spodoptera-frugiperda-cells
#5
Jingfeng Li, Yu Sun, Yuying Li, Ximeng Liu, Qi Yue, Zhaofei Li
Fatty acid synthase (FASN) catalyzes the synthesis of palmitate, which is required for formation of complex fatty acids and phospholipids that are involved in energy production, membrane remodeling and modification of host and viral proteins. Presently, the roles of cellular fatty acid synthesis pathway in Autographa californica multiple nucleopolyhedrovirus (AcMNPV) infection is not clear. In this study, we found that the transcripts level of fasn was significantly up-regulated at the early stage of AcMNPV infection...
May 7, 2018: Virus Research
https://www.readbyqxmd.com/read/29743929/neonatal-overfeeding-induced-glucocorticoid-overexposure-accelerates-hepatic-lipogenesis-in-male-rats
#6
Fan Yang, Yanyan Dai, Cuiting Min, Xiaonan Li
Background: Postnatal overfeeding activates tissue glucocorticoid (GC) activity by up-regulating 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and increasing sensitivity to high-fat (HF) diet-induced non-alcoholic fatty liver disease (NAFLD). The present study aimed to evaluate the effects of postnatal overfeeding on GC regulation and lipogenesis in the liver and to observe the impact of GC on hepatocyte lipid metabolism. Methods: In vivo , Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litter, SL) or ten (normal litter, NL) on postnatal day 3 and then given standard chow from postnatal week 3 (W3) to W13...
2018: Nutrition & Metabolism
https://www.readbyqxmd.com/read/29738703/high-fat-diet-induced-obesity-is-mitigated-in-cyp3a-null-female-mice
#7
Ramiya Kumar, Elizabeth J Litoff, W Tyler Boswell, William S Baldwin
Recent studies indicate a role for the constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity. Therefore, we examined whether Cyp3a-null mice show increased obesity and fatty liver disease following 8-weeks of exposure to a 60% high-fat diet (HFD). Surprisingly, HFD-fed Cyp3a-null females fed a HFD gained 50% less weight than wild-type (WT; B6) females fed a HFD. In contrast, Cyp3a-null males gained more weight than WT males, primarily during the first few weeks of HFD-treatment...
May 5, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29723075/orlistat-as-a-fasn-inhibitor-and-multitargeted-agent-for-cancer-therapy
#8
Alejandro Schcolnik-Cabrera, Alma Chávez-Blanco, Guadalupe Domínguez-Gómez, Lucia Taja-Chayeb, Rocio Cardenas-Barcenas, Catalina Trejo-Becerril, Enrique Perez-Cardenas, Aurora Gonzalez-Fierro, Alfonso Dueñas-González
Cancer cells have increased glycolysis and glutaminolysis. Their third feature is increased de novo lipogenesis. As such, fatty acid (FA) synthesis enzymes are over-expressed in cancer and their depletion causes antitumor effects. As fatty acid synthase (FASN) plays a pivotal role in this process, it is an attractive target for cancer therapy. Areas covered: This is a review of the lipogenic phenotype of cancer and how this phenomenon can be exploited for cancer therapy using inhibitors of FASN, with particular emphasis on orlistat as a repurposing drug...
May 3, 2018: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29698466/profiling-of-epidermal-lipids-in-a-mouse-model-of-dermatitis-identification-of-potential-biomarkers
#9
Jackeline Franco, Christina Ferreira, Tiago J Paschoal Sobreira, John P Sundberg, Harm HogenEsch
Lipids are important structural and functional components of the skin. Alterations in the lipid composition of the epidermis are associated with inflammation and can affect the barrier function of the skin. SHARPIN-deficient cpdm mice develop a chronic dermatitis with similarities to atopic dermatitis in humans. Here, we used a recently-developed approach named multiple reaction monitoring (MRM)-profiling and single ion monitoring to rapidly identify discriminative lipid ions. Shorter fatty acyl residues and increased relative amounts of sphingosine ceramides were observed in cpdm epidermis compared to wild type mice...
2018: PloS One
https://www.readbyqxmd.com/read/29687616/percutaneous-muscle-biopsy-induced-tissue-injury-causes-local-endoplasmic-reticulum-stress
#10
Jun Yoshino, Paloma Almeda-Valdes, Anna C Moseley, Bettina Mittendorfer, Samuel Klein
Endoplasmic reticulum (ER) stress is likely involved in the pathogenesis of metabolic dysfunction in people with obesity and diabetes. Although tissue biopsy is often used to evaluate the presence and severity of ER stress, it is not known whether acute tissue injury-induced by percutaneous muscle biopsy causes ER stress and its potential downstream effects on markers of inflammation and metabolic function. In this study, we tested the hypothesis that percutaneous biopsy-induced tissue injury causes ER stress and alters inflammatory and metabolic pathways in skeletal muscle...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29684438/the-cytoskeleton-in-couch-potato-ism-insights-from-a-murine-model-of-impaired-actin-dynamics
#11
Karen Gertz, Ria Uhlemann, Anna Foryst-Ludwig, Ruben Marquina Barrientos, Kai Kappert, Christa Thöne-Reineke, Pierre Djoufack, Clemens Kirschbaum, Klaus B Fink, Andreas Heinz, Ulrich Kintscher, Matthias Endres, Golo Kronenberg
Evidence for a critical pathophysiological role of aberrant cytoskeletal dynamics is being uncovered in a growing number of neuropsychiatric syndromes. A sedentary lifestyle as well as overt psychopathology is prevalent in patients with the metabolic syndrome. Using mice deficient in gelsolin (Gsn-/- ), a crucial actin-severing protein, we here investigated reduced actin turnover as a potential common driver of metabolic disturbances, sedentary behavior, and an anxious/depressive phenotype. Gelsolin deficiency resulted in reduced lifespan...
April 20, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29680640/overexpression-of-srebf-chaperone-scap-enhances-nuclear-srebp1-translocation-to-upregulate-fatty-acid-synthase-fasn-gene-expression-in-bovine-mammary-epithelial-cells
#12
L Q Han, T Y Gao, G Y Yang, J J Loor
Fatty acid synthase is a key enzyme for the synthesis of milk fat in the ruminant mammary gland. In nonruminants, sterol regulatory element binding protein 1 (SREBP1) is a regulator of FASN gene expression, and SREBF chaperone (SCAP) is essential for SREBP1 maturation and activity. However, the role of SCAP on the regulation of FASN gene expression in ruminants is unknown. The objective of this study was to investigate the transcriptional regulation of FASN by overexpressing SCAP in bovine mammary epithelial cells...
April 18, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29668854/prostate-cancer-chemoprevention-by-sulforaphane-in-a-preclinical-mouse-model-is-associated-with-inhibition-of-fatty-acid-metabolism
#13
Krishna B Singh, Su-Hyeong Kim, Eun-Ryeong Hahm, Subrata K Pore, Bruce L Jacobs, Shivendra V Singh
Increased de novo synthesis of fatty acids is a rather unique and targetable mechanism of human prostate cancer. We have shown previously that oral administration of sulforaphane (SFN) significantly inhibits the incidence and/or burden of prostatic intraepithelial neoplasia and well-differentiated adenocarcinoma in TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice. The present study used cellular models of prostate cancer and archived plasma/adenocarcinoma tissues and sections from the TRAMP study to demonstrate inhibition of fatty acid synthesis by SFN treatment in vitro and in vivo...
April 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29642504/alteration-of-hepatic-gene-expression-along-with-the-inherited-phenotype-of-acquired-fatty-liver-in-chicken
#14
Yonghong Zhang, Zhen Liu, Ranran Liu, Jie Wang, Maiqing Zheng, Qinghe Li, Huanxian Cui, Guiping Zhao, Jie Wen
Fatty liver is a widespread disease in chickens that causes a decrease in egg production and even death. The characteristics of the inherited phenotype of acquired fatty liver and the molecular mechanisms underlying it, however, are largely unknown. In the current study, fatty liver was induced in 3 breeds by a high-fat (HF) diet and a methionine choline-deficient (MCD) diet. The results showed that the dwarf Jingxing-Huang (JXH) chicken was more susceptible to fatty liver compared with the layer White Leghorns (WL) and local Beijing-You (BJY) breeds...
April 8, 2018: Genes
https://www.readbyqxmd.com/read/29626799/lipid-reducing-activity-and-toxicity-profiles-of-a-library-of-polyphenol-derivatives
#15
Ralph Urbatzka, Sara Freitas, Andreia Palmeira, Tiago Almeida, João Moreira, Carlos Azevedo, Carlos Afonso, Marta Correia-da-Silva, Emilia Sousa, Madalena Pinto, Vitor Vasconcelos
Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo...
March 23, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29620215/integrated-analysis-of-the-gene-expression-profile-and-dna-methylation-profile-of-obese-patients-with-type-2-diabetes
#16
Juan Shen, Bin Zhu
In order to better understand the etiology of obese type 2 diabetes (T2D) at the molecular level, the present study investigated the gene expression and DNA methylation profiles associated with T2D via systemic analysis. Gene expression (GSE64998) and DNA methylation profiles (GSE65057) from liver tissues of healthy controls and obese patients with T2D were downloaded from the Gene Expression Omnibus database. Differentially‑expressed genes (DEGs) and differentially‑methylated genes (DMGs) were identified using the Limma package, and their overlapping genes were additionally determined...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619215/proteomic-analysis-of-adipose-tissue-during-the-last-weeks-of-gestation-in-pure-and-crossbred-large-white-or-meishan-fetuses-gestated-by-sows-of-either-breed
#17
F Gondret, B Guével, M C Père, H Quesnel, Y Billon, E Com, L Canario, I Louveau, L Liaubet
Background: The degree of adipose tissue development at birth may influence neonatal survival and subsequent health outcomes. Despite their lower birth weights, piglets from Meishan sows (a fat breed with excellent maternal ability) have a higher survival rate than piglets from Large White sows (a lean breed). To identify the main pathways involved in subcutaneous adipose tissue maturation during the last month of gestation, we compared the proteome and the expression levels of some genes at d 90 and d 110 of gestation in purebred and crossbred Large White or Meishan fetuses gestated by sows of either breed...
2018: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29614102/does-growth-path-influence-beef-lipid-deposition-and-fatty-acid-composition
#18
Ana S H Costa, Paulo Costa, Susana P Alves, Cristina M Alfaia, José A M Prates, Veronica Vleck, Isabelle Cassar-Malek, Jean-François Hocquette, Rui J B Bessa
Despite the recent advances in transcriptomics, gene expression studies addressing cattle´s skeletal muscle adaptations in response to compensatory growth are warranted, particularly regarding lipid metabolism due to its impact in meat sensory and nutritional traits. In the present study, in comparison to ad libitum feeding, a period of feed restriction was used in order to understand the changes in bull´s lipid metabolism and gene expression of the adipogenic and lipogenic pathways after re-alimentation...
2018: PloS One
https://www.readbyqxmd.com/read/29593575/dai-zong-fang-a-traditional-chinese-herbal-formula-ameliorates-insulin-resistance-in-db-db-mice
#19
Lili Zhu, Xiaoyun Zhu, Guibo Sun, Xiangbao Meng, Min Wang, Hanming Cui, Jialong Wang, Yadong Zhai, Ke Yang, Yang Tang, Xiaobo Sun, Ximing Liu
Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db -/- ( db/db ) mice...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29588626/epistructured-catechins-egcg-and-ec-facilitate-apoptosis-induction-through-targeting-de-novo-lipogenesis-pathway-in-hepg2-cells
#20
Phuriwat Khiewkamrop, Pattamaphron Phunsomboon, Lysiane Richert, Dumrongsak Pekthong, Piyarat Srisawang
Background: Abnormally high expression of the mammalian de novo lipogenesis (DNL) pathway in various cancer cells promotes cell over-proliferation and resistance to apoptosis. Inhibition of key enzymes in the DNL pathway, namely, ATP citrate lyase, acetyl-CoA carboxylase, and fatty acid synthase (FASN) can increase apoptosis without cytotoxicity to non-cancerous cells, leading to the search for and presentation of novel selective and powerful targets for cancer therapy. Previous studies reported that epistructured catechins, epigallocatechin gallate (EGCG) and epicatechin (EC) exhibit different mechanisms regarding a strong inducer of apoptosis in various cancer cell lines...
2018: Cancer Cell International
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