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https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#1
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28205174/identifying-sterol-response-elements-within-promoters-of-genes
#2
Laura J Sharpe, Andrew J Brown
Cholesterol levels are under tight control within cells. This involves a complex interplay of balancing synthesis, uptake, and export. A major player in the transcriptional regulation of cholesterol levels is sterol regulatory element binding protein (SREBP). SREBP is upregulated in conditions of low cholesterol, and then binds to sterol regulatory elements (SREs) that exist within the promoters of genes involved in cholesterol synthesis and uptake.Here, we describe a method to identify sterol response elements (SREs) using in silico and experimental approaches...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28204815/enzyme-treated-ecklonia-cava-extract-inhibits-adipogenesis-through-the-downregulation-of-c-ebp%C3%AE-in-3t3-l1-adipocytes
#3
In-Hye Kim, Taek-Jeong Nam
In this study, we examined the inhibitory effects of enzyme- treated Ecklonia cava (EEc) extract on the adipogenesis of 3T3-L1 adipocytes. The components of Ecklonia cava (E. cava) were first separated and purified using the digestive enzymes pectinase (Rapidase® X‑Press L) and cellulase (Rohament® CL). We found that the EEc extract contained three distinct phlorotannins: eckol, dieckol and phlorofucofuroeckol-A. Among the phlorotannins, dieckol was the most abundant in the EEc extract at 16 mg/g. Then we examined the inhibitory effects of EEc extract treatment on differentiation‑related transcription factors and on adipogenesis‑related gene expression in vitro using 3T3-L1 adipocytes...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203225/regulation-of-sterol-biosynthesis-in-the-human-fungal-pathogen-aspergillus-fumigatus-opportunities-for-therapeutic-development
#4
REVIEW
Sourabh Dhingra, Robert A Cramer
Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202541/coordinate-regulation-of-yeast-sterol-regulatory-element-binding-protein-srebp-and-mga2-transcription-factors
#5
Risa Burr, Emerson V Stewart, Peter J Espenshade
The Mga2 and Sre1 transcription factors regulate oxygen-responsive lipid homeostasis in the fission yeast Schizosaccharomyces pombe in a manner analogous to the mammalian Sterol Regulatory Element-Binding Protein transcription factors SREBP-1 and SREBP-2. Mga2 and SREBP-1 regulate triacylglycerol and glycerophospholipid synthesis, while Sre1 and SREBP-2 regulate sterol synthesis. In mammals, a shared activation mechanism allows for coordinate regulation of SREBP-1 and SREBP-2. In contrast, distinct pathways activate fission yeast Mga2 and Sre1...
February 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28190475/calycosin-attenuates-triglyceride-accumulation-and-hepatic-fibrosis-in-murine-model-of-non-alcoholic-steatohepatitis-via-activating-farnesoid-x-receptor
#6
Xingping Duan, Qiang Meng, Changyuan Wang, Zhihao Liu, Qi Liu, Huijun Sun, Pengyuan Sun, Xiaobo Yang, Xiaokui Huo, Jinyong Peng, Kexin Liu
BACKGROUND: Non-alcoholic steatohepatitis (NASH) represents the more severe end of hepatic steatosis and is associated with progressive liver disease. Calycosin, derived from the root of Radix Astragali, has been demonstrated to have favorable efficacy on acute liver injury. PURPOSE: The present study was to investigate the hepatoprotective effect of calycosin on attenuating triglyceride accumulation and hepatic fibrosis, as well as explore the potential mechanism in murine model of NASH...
February 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28184028/long-term-administration-of-tacrolimus-and-everolimus-prevents-high-cholesterol-high-fructose-induced-steatosis-in-c57bl-6j-mice-by-inhibiting-de-novo-lipogenesis
#7
Sharma Love, Malik A Mudasir, Subhash C Bhardwaj, Gurdarshan Singh, Sheikh A Tasduq
AIM: To investigate the effects of tacrolimus (TC) and everolimus (EV) on non-alcoholic steatohepatitis (NASH) induced by high fat, high cholesterol and fructose (fast food) diet in C57BL/6J mice. MATERIALS AND METHODS: C57BL/6J mice were divided into four groups (n=8). 1) Standard Chow (SC); 2) Fast food (FF) diet; 3) FF + Tacrolimus (TC, 1mg/kg) and; 4) FF + Everolimus (EV, 1mg/kg) and treated for 16 weeks. Serum and tissue samples were analyzed for evidence of inflammation, fibrosis, lipogenesis, and apoptosis...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28179493/nutritional-and-lipid-modulation-of-pcsk9-effects-on-cardiometabolic-risk-factors
#8
REVIEW
Jacqueline A Krysa, Teik Chye Ooi, Spencer D Proctor, Donna F Vine
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a serine protease involved in the regulation of LDL receptor (LDLR) expression and apolipoprotein B lipoprotein cholesterol metabolism. Hepatic PCSK9 protein expression, activity, and secretion have been shown to affect cholesterol homeostasis. An upregulation of hepatic PSCK9 protein leads to increased LDLR degradation, resulting in decreased uptake of apoB lipoproteins and a consequent increase in the plasma concentration of these lipoproteins, including LDL and chylomicron remnants...
February 8, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28168742/astrocyte-lipid-metabolism-is-critical-for-synapse-development-and-function-in-vivo
#9
Anne-Lieke F van Deijk, Nutabi Camargo, Jaap Timmerman, Tim Heistek, Jos F Brouwers, Floriana Mogavero, Huibert D Mansvelder, August B Smit, Mark H G Verheijen
The brain is considered to be autonomous in lipid synthesis with astrocytes producing lipids far more efficiently than neurons. Accordingly, it is generally assumed that astrocyte-derived lipids are taken up by neurons to support synapse formation and function. Initial confirmation of this assumption has been obtained in cell cultures, but whether astrocyte-derived lipids support synapses in vivo is not known. Here, we address this issue and determined the role of astrocyte lipid metabolism in hippocampal synapse formation and function in vivo...
February 7, 2017: Glia
https://www.readbyqxmd.com/read/28167099/27-hydroxycholesterol-regulates-cholesterol-synthesis-and-transport-in-c6-glioma-cells
#10
Yu An, Dan-Di Zhang, Huan-Ling Yu, Wei-Wei Ma, Yan-Hui Lu, Quan-Ri Liu, Rong Xiao
The oxysterol 27-Hydroxycholesterol (27-OHC) is a major cholesterol metabolite that can cross the blood brain barrier (BBB) from peripheral circulation to the brain. Currently, the role of 27-OHC on cholesterol homeostasis in astrocytes and the underlying mechanisms are not defined. Since all brain cholesterol is essentially synthesized in brain itself and astrocytes as net producers of cholesterol are essential for normal brain function, here we investigated the effects of 27-OHC on cholesterol synthesis and transport in C6 glioma cells...
February 3, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28164196/preventive-effect-of-silibinin-in-combination-with-pu-erh-tea-extract-on-non-alcoholic-fatty-liver-disease-in-ob-ob-mice
#11
Wen-Yi Hu, Xiao-Hui Ma, Wang-Yi Zhou, Xin-Xin Li, Ting-Ting Sun, He Sun
There are presently no miracle drugs for non-alcoholic fatty liver disease (NAFLD). This study investigates the synergistic effect of Silibinin combined with Pu-erh tea extract (PTE) against NAFLD and explores the suggested mechanism of action. Ob/ob mice were fed a high fat diet along with the oral administration of Silibinin (86 mg per kg per day), PTE (250 mg per kg per day) or their combination for 6 weeks. Their lean littermates who were fed with standard chow diet were used as the control group. The blood biochemical index and histopathological evaluation were analyzed...
February 6, 2017: Food & Function
https://www.readbyqxmd.com/read/28161992/antrodia-cinnamomea-prevents-obesity-dyslipidemia-and-the-derived-fatty-liver-via-regulating-ampk-and-srebp-signaling
#12
Chiung-Huei Peng, Mon-Yuan Yang, Yi-Sun Yang, Chieh-Chou Yu, Chau-Jong Wang
Antrodia cinnamomea (AC), a protogenic fungus that only grows on the heartwood of endemic Cinnamomum kanehirae Hayata in Taiwan, is used to treat a variety of illness including liver disease. However, little is known about the benefit of AC against obesity and the related hepatic disorder. Using high-fat-diet (HFD) feed mice, we aimed to investigate whether the extract of AC (ACE) could reduce excessive weight, body fat, and serum lipids and prevent the development of non-alcoholic fatty liver (NAFLD). C57BL/6 mice were divided into five groups fed with different diets: control, HFD, and HFD with 0...
2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28157400/nuclear-factor-of-%C3%AE%C2%BAb1-is-a-key-regulator-for-the-transcriptional-activation-of-milk-synthesis-in-bovine-mammary-epithelial-cells
#13
Xin Huang, Yanli Zang, Minghui Zhang, Xiaohan Yuan, Meng Li, Xuejun Gao
The nuclear factor of κB (NFκB) family has been well known for its significant role in regulating the expression of numerous genes that control many biological processes. However, it is unclear whether NFκB could regulate milk synthesis. In this study, we identified NFκB1 as a critical regulator for milk synthesis in bovine mammary epithelial cells (BMECs). Gene function study revealed that NFκB1 modulates the expression of mammalian target of rapamycin (mTOR), sterol response element-binding protein (SREBP)-1c, and β4Gal-T2 for milk synthesis...
February 3, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28146130/effects-of-natural-products-on-fructose-induced-nonalcoholic-fatty-liver-disease-nafld
#14
REVIEW
Qian Chen, Tingting Wang, Jian Li, Sijian Wang, Feng Qiu, Haiyang Yu, Yi Zhang, Tao Wang
As a sugar additive, fructose is widely used in processed foods and beverages. Excessive fructose consumption can cause hepatic steatosis and dyslipidemia, leading to the development of metabolic syndrome. Recent research revealed that fructose-induced nonalcoholic fatty liver disease (NAFLD) is related to several pathological processes, including: (1) augmenting lipogenesis; (2) leading to mitochondrial dysfunction; (3) stimulating the activation of inflammatory pathways; and (4) causing insulin resistance...
January 31, 2017: Nutrients
https://www.readbyqxmd.com/read/28134973/fucosterol-isolated-from-ecklonia-stolonifera-inhibits-adipogenesis-through-modulation-of-foxo1-pathway-in-3t3-l1-adipocytes
#15
Ji-Hyun Lee, Hyun Ah Jung, Min Jae Kang, Jae Sue Choi, Gun-Do Kim
OBJECTIVES: The purpose of this study was to investigate the effects of fucosterol on adipogenesis of 3T3-L1 preadipocytes and its underlying mechanisms. METHODS: Fucosterol, isolated from brown algae, Ecklonia stolonifera. We investigated the levels of lipid accumulation using Oil Red O staining. We conducted Western blot analysis to investigate regulatory effects of fucosterol on expression of phosphoinositide 3-kinase (PI3K), Akt, extracellular signal-regulated kinase (ERK), forkhead box protein O 1 (FoxO1) in 3T3-L1 adipocytes...
March 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28132894/vitamin-d-metabolite-25-hydroxyvitamin-d-regulates-lipid-metabolism-by-inducing-degradation-of-srebp-scap
#16
Lisa Asano, Mizuki Watanabe, Yuta Ryoden, Kousuke Usuda, Takuya Yamaguchi, Bilon Khambu, Megumi Takashima, Shin-Ichi Sato, Juro Sakai, Kazuo Nagasawa, Motonari Uesugi
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. SREBP activation is regulated by a negative feedback loop in which sterols bind to SREBP cleavage-activating protein (SCAP), an escort protein essential for SREBP activation, or to insulin-induced genes (Insigs) (endoplasmic reticulum [ER] anchor proteins), sequestering the SREBP-SCAP-Insig complex in the ER. We screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBP activation...
January 23, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28131831/response-of-genes-involved-in-lipid-metabolism-in-rat-epididymal-white-adipose-tissue-to-different-fasting-conditions-after-long-term-fructose-consumption
#17
Jin-Xiu Li, Da-Zhi Ke, Ling Yao, Shang Wang, Peng Ma, Li Liu, Guo-Wei Zuo, Li-Rong Jiang, Jian-Wei Wang
There has been much concern regarding the dietary fructose contributes to the development of metabolic syndrome. High-fructose diet changes the expression of genes involved in lipid metabolism. Levels of a number of hepatic lipogenic enzymes are increased by a high-carbohydrate diet in fasted-refed model rats/mice. Both the white adipose tissue (WAT) and the liver play a key role in the maintenance of nutrient homeostasis. Here, the aim of this study was to analyze the expression of key genes related to lipid metabolism in epididymal WAT (eWAT) in response to different fasting condition after long-term chronic fructose consumption...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28128380/effects-of-rosa-mosqueta-oil-supplementation-in-lipogenic-markers-associated-with-prevention-of-liver-steatosis
#18
Camila G Dossi, Cynthia Cadagan, Marcela San Martín, Alejandra Espinosa, Daniel González-Mañán, David Silva, Rodrigo A Mancilla, Gladys S Tapia
Rosa mosqueta (RM) oil is rich in α-linolenic acid (ALA) - a precursor of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), and it has a high antioxidant activity due to its abundant content of tocopherols. Additionally, it has been observed that RM oil administration prevents hepatic steatosis. Thus, the aim of this study was to demonstrate the antilipogenic mechanism related to RM oil administration in a high-fat diet (HFD) fed mice model by evaluating markers associated with the regulation of lipid droplet metabolism (PLIN2, PLIN5 and PPAR-γ), and proteins associated with lipogenesis (FAS and SREBP-1c)...
January 27, 2017: Food & Function
https://www.readbyqxmd.com/read/28128372/the-hepatoprotective-effect-of-phyllanthus-emblica-l-fruit-on-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-nafld-in-sd-rats
#19
Cheng-Ze Huang, Yu-Tang Tung, Shih-Min Hsia, Chi-Hao Wu, Gow-Chin Yen
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with metabolic syndrome and refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. Phyllanthus emblica L. is a rich source of gallic acid and many known medicinally phytochemicals such as tannins, lignans, flavonoids, alkaloids, vitamin C, mucic acid, and ellagic acid. Our previous study has revealed that P. emblica exhibits inhibitory effects on hepatic steatosis and liver fibrosis in vitro, as well as gallic acid improves high fat diet (HFD)-induced dyslipidaemia, hepatosteatosis, and oxidative stress in vivo...
January 27, 2017: Food & Function
https://www.readbyqxmd.com/read/28123944/celastrol-ameliorates-liver-metabolic-damage-caused-by-a-high-fat-diet-through-sirt1
#20
Yinliang Zhang, Chao Geng, Xiaoyan Liu, Meixia Li, Mingyue Gao, Xiaojun Liu, Fude Fang, Yongsheng Chang
OBJECTIVE: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. METHODS: Functional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. RESULTS: When WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations...
January 2017: Molecular Metabolism
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