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Ritu S Sharma, David J Harrison, Dorothy Kisielewski, Diane M Cassidy, Alison D McNeilly, Jennifer R Gallagher, Shaun V Walsh, Tadashi Honda, Rory J McCrimmon, Albena T Dinkova-Kostova, Michael L J Ashford, John F Dillon, John D Hayes
Background & Aims: Nonalcoholic steatohepatitis (NASH) is associated with oxidative stress. We surmised that pharmacologic activation of NF-E2 p45-related factor 2 (Nrf2) using the acetylenic tricyclic bis(cyano enone) TBE-31 would suppress NASH because Nrf2 is a transcriptional master regulator of intracellular redox homeostasis. Methods: Nrf2 +/+ and Nrf2 -/- C57BL/6 mice were fed a high-fat plus fructose (HFFr) or regular chow diet for 16 weeks or 30 weeks, and then treated for the final 6 weeks, while still being fed the same HFFr or regular chow diets, with either TBE-31 or dimethyl sulfoxide vehicle control...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Taewon Yuk, Younghwa Kim, Jinwoo Yang, Jeehye Sung, Heon Sang Jeong, Junsoo Lee
We aimed to investigate the effects of nobiletin on hepatic lipogenesis in high glucose-induced lipid accumulation in HepG2 cells. Nobiletin, a citrus polymethoxyflavonoid with six methoxy groups, is present abundantly in the peels of citrus fruits. HepG2 cells were incubated in Dulbecco's modified Eagle's medium containing high glucose (25 mM) and subsequently treated with nobiletin at different concentrations (5, 25, and 50  μ M). Results showed that nobiletin markedly inhibited high glucose-induced hepatic lipid accumulation in HepG2 cells...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Pengfei Xu, Fan Hong, Jing Wang, Shu Dai, Jialin Wang, Yonggong Zhai
Constitutive androstane receptor (CAR) is a nuclear receptor that not only regulates drug-metabolizing enzymes but also influences energy metabolism. TC, 1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene (TCPOBOP) has been shown to inhibit lipogenesis in the liver and adipose tissues. The mammary gland is mainly composed of fat pads and duct systems in adolescent female mice. Here, activation of CAR by TC reduces the mammary gland weight, blocks lipid accumulation by inhibiting lipogenesis and gluconeogenesis, and accelerates collagen formation and fibrosis in the mammary fat pad of adolescent female mice...
March 14, 2018: Toxicology Letters
Ondrej Kuda, Marie Brezinova, Jan Silhavy, Vladimir Landa, Vaclav Zidek, Chandra Dodia, Franziska Kreuchwig, Marek Vrbacky, Laurence Balas, Thierry Durand, Norbert Hübner, Aron B Fisher, Jan Kopecky, Michal Pravenec
Fatty acid esters of hydroxy fatty acids (FAHFAs) are lipid mediators with promising anti-diabetic and anti-inflammatory properties that are formed in white adipose tissue (WAT) via de novo lipogenesis, but their biosynthetic enzymes are unknown. Using a combination of lipidomics in WAT, QTL mapping and correlation analyses in rat BXH/HXB recombinant inbred strains, and response to oxidative stress in murine models, we elucidated the potential pathway of biosynthesis of several FAHFAs.Comprehensive analysis of WAT samples identified ∼160 regioisomers documenting the complexity of this lipid class...
March 16, 2018: Diabetes
Yuyan Zhu, Chih-Yu Chen, Junjie Li, Ji-Xin Cheng, Miran Jang, Kee-Hong Kim
As adipose tissue is the major cholesterol storage organ and most of the intracellular cholesterol is distributed to lipid droplets (LDs), cholesterol homeostasis may have a role in the regulation of adipocyte size and function. ACAT catalyze the formation of cholesteryl ester from free cholesterol modulate the cholesterol balance. Despite the well-documented role of ACATs in hypercholesterolemia, their role in LD development during adipogenesis remains elusive. Here, we identify ACATs as regulators of de novo lipogenesis and LD formation in murine 3T3-L1 adipocytes...
March 16, 2018: Journal of Lipid Research
Hilal Ahmad Parray, Jameel Lone, Jong Pil Park, Jang Won Choi, Jong Won Yun
OBJECTIVE: The aim of this study was to explore the browning and antioxidative effects of magnolol in 3T3-L1 adipocytes, as recruitment of beige-like adipocytes (browning) by natural compounds is being considered as a promising strategy to fight against obesity. METHODS: Magnolol-induced browning effect was evaluated by determining the expression levels of specific marker genes and proteins using real-time polymerase chain reaction and immunoblotting, respectively...
February 5, 2018: Nutrition
Bastian Ramms, Philip L S M Gordts
PURPOSE OF REVIEW: Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. RECENT FINDINGS: APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements...
March 15, 2018: Current Opinion in Lipidology
Yun Hu, Qinwei Sun, Yan Hu, Zhen Hou, Yibo Zong, Nagmeldin A Omer, Halima Abobaker, Ruqian Zhao
Background: We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. Objective: In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms...
March 1, 2018: Journal of Nutrition
Wan-Angkan Poolsri, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, Piyarat Srisawang
Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy...
2018: BioMed Research International
Tian-Xing Chen, Xiao-Ying Cheng, Yun Wang, Wu Yin
Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins α (C/EBP-α), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes...
March 15, 2018: Scientific Reports
Enxiang Zhang, Shutao Yin, Xiaotong Lu, Linhu Ye, Lihong Fan, Hongbo Hu
Glycycoumarin (GCM) is a representative of bioactive coumarin compounds isolated from licorice, an edible and medicinal plant widely used for treating various diseases including liver diseases. The purpose of the present study is to examine the possibility of GCM as a sensitizer to improve the efficacy of BH3 mimetic ABT-737 against liver cancer. Three liver cancer cell lines (HepG2, Huh-7 and SMMC-7721) were used to evaluate the in vitro combinatory effect of ABT-737/GCM. HepG2 xenograft model was employed to assess the in vivo efficacy of ABT-737/GCM combination...
March 15, 2018: Nutrients
Raffaella Mastrocola, Ilario Ferrocino, Erica Liberto, Fausto Chiazza, Alessia Sofia Cento, Debora Collotta, Giulia Querio, Debora Nigro, Valeria Bitonto, Juan Carlos Cutrin, Kalliopi Rantsiou, Mariaconcetta Durante, Emanuela Masini, Manuela Aragno, Chiara Cordero, Luca Cocolin, Massimo Collino
Despite clinical findings suggesting that the form (liquid versus solid) of the sugars may significantly affect the development of metabolic diseases, no experimental data are available on the impact of their formulations on gut microbiota, integrity and hepatic outcomes. In the present sudy, C57Bl/6j mice were fed a standard diet plus water (SD), a standard diet plus 60% fructose syrup (L-Fr) or a 60% fructose solid diet plus water (S-Fr) for 12 weeks. Gut microbiota was characterized through 16S rRNA phylogenetic profiling and shotgun sequencing of microbial genes in ileum content and related volatilome profiling...
February 13, 2018: Journal of Nutritional Biochemistry
Deqiang Zhang, Xin Tong, Bradley B Nelson, Ethan Jin, Julian Sit, Nicholas Charney, Meichan Yang, M Bishr Omary, Lei Yin
Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show that the circadian clock protein BMAL1 in hepatocytes is both necessary and sufficient to protect mice from alcohol liver disease. Ethanol diet-fed mice with liver-specific knockout (Bmal1-LKO) or depletion of Bmal1 develop more severe liver steatosis and injury as well as a simultaneous suppression of both de novo lipogenesis and fatty acid oxidation, which can be rescued by the supplementation of synthetic PPARα ligands...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Long The Nguyen, Hui Chen, Crystal Mak, Amgad Zaky, Carol Pollock, Sonia Saad
Recent studies indicate that SIRT1, an important metabolic sensor and regulator of lifespan, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high-fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (SRT, 25mg/kg/2days i...
March 13, 2018: American Journal of Physiology. Endocrinology and Metabolism
Liang Lu, Zhiqin Wan, Ting Luo, Zhengwei Fu, Yuanxiang Jin
Microplastic (MP) has become a concerning global environmental problem. It is toxic to aquatic organisms and can spread through the food chain to ultimately pose a threat to humans. In the environment, MP can interact with microbes and act as a microbial habitat. However, effects of polystyrene MP on the gut microbiota in mammals remain unclear. Here, male mice were exposed to two different sizes of polystyrene MP for 5 weeks to explore its effect. We observed that oral exposure to 1000 μg/L of 0.5 and 50 μm polystyrene MP decreased the body, liver and lipid weights in mice...
March 9, 2018: Science of the Total Environment
Dandan Huang, Baoqing Liu, Kai Huang, Kun Huang
Metabolic disorders, including obesity, non-alcoholic fatty liver disease (NAFLD), metabolic syndrome and diabetes, are complex and progressive diseases. Enoyl coenzyme A hydratase 1 (Ech1) is an enzyme that participates in mitochondrial fatty acid β-oxidation; however, little is known regarding the significance of Ech1 in the pathogenesis of metabolic disorders. Here, we report that high-fat-diet (HFD)-induced and genetic obesity could increase Ech1 expression in mouse liver. The overexpression of Ech1 using adeno-associated virus (AAV2/8) ameliorated HFD-induced liver lipid accumulation and accompanying liver injury...
March 8, 2018: Biochemical and Biophysical Research Communications
Cornelia M Weyand, Yi Shen, Jorg Goronzy
Reactive oxygen species (ROS) are byproducts of oxygen metabolism best known for their damaging potential, but recent evidence has exposed their role as secondary messengers, which regulate cell function through redox-activatable signaling systems. In immune cells, specifically in T cells, redox-sensitive signaling pathways have been implicated in controlling several functional domains; including cell cycle progression, T effector cell differentiation, tissue invasion and inflammatory behavior. T cells from patients with the autoimmune disease rheumatoid arthritis (RA) have emerged as a valuable model system to examine the functional impact of ROS on T cell function...
March 7, 2018: Free Radical Biology & Medicine
Yan-Ling Zhu, Ting Chen, Jia-Li Xiong, Di Wu, Qian-Yun Xi, Jun-Yi Luo, Jia-Jie Sun, Yong-Liang Zhang
Adipose tissue plays an important role in energy metabolism. Adipose dysfunction is closely related to obesity and type II diabetes. Glucose uptake is the key step for fat synthesis in adipocyte. miRNAs have been proven to play a crucial role in adipocyte differentiation, adipogenesis and glucose homeostasis. In this paper, we firstly reported that miR-146b decreased glucose consumption by up-regulating miR-146b in a porcine primary adipocyte model, while the inhibitor of endogenous miR-146b rescued the reduction...
March 9, 2018: International Journal of Molecular Sciences
Krzysztof Wrzesinski, Stephen J Fey
The recovery of physiological functionality, which is commonly seen in tissue mimetic three-dimensional (3D) cellular aggregates (organoids, spheroids, acini, etc.), has been observed in cells of many origins (primary tissues, embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and immortal cell lines). This plurality and plasticity suggest that probably several basic principles promote this recovery process. The aim of this study was to identify these basic principles and describe how they are regulated so that they can be taken in consideration when micro-bioreactors are designed...
March 7, 2018: Bioengineering
Xiaoping Zhao, Li Zhao, Hao Yang, Jiajin Li, Xuejie Min, Fajun Yang, Jianjun Liu, Gang Huang
Dysregulation of lipid metabolism is common in cancer cells, but the underlying mechanisms are poorly understood. Sterol regulatory element-binding proteins (SREBPs) stimulate lipid biosynthesis through transcriptional activation of lipogenic enzymes. However, SREBPs' roles and potential interacting partners in cancer cells are not fully defined. Using a biochemical approach, we found here that pyruvate kinase M2 (PKM2) physically interacts with the nuclear form of SREBP-1a (nBP1a), by binding to amino acids 43-56 in nBP1a...
March 7, 2018: Journal of Biological Chemistry
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