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Choline AND Triglycerides

Amar Bahadur Singh, Jingwen Liu
Peroxisome proliferator-activated receptor δ (PPARδ) regulates many genes involved in lipid metabolism. Hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) has critical functions in triglycerides transport and ER stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Previous studies identified liver X receptor as the transcription factor controlling LPCAT3 expression in mouse liver tissue. Here we show that the hepatic LPCAT3 gene is transcriptionally regulated by PPARδ...
December 2, 2016: Journal of Biological Chemistry
Jie Zhu, Ting Lu, Fei Chen, Junkai Yan, Fan Chen, Qiaosen Zhang, Jifan Wang, Weihui Yan, Tingxi Yu, Qingya Tang, Wei Cai
BACKGROUND: Deficiency of choline, a required nutrient, is related to intestinal failure-associated liver disease (IFALD). Therefore, we aimed to investigate the effects of choline supplementation on IFALD and the underlying mechanisms. METHODS: Male Sprague-Dawley rats (4 weeks old) were fed AIN-93G chow and administered intravenous 0.9% saline (control), parenteral nutrition (PN), or PN plus intravenous choline (600 mg/kg) for 7 days. We evaluated body weight, hepatic histology, biochemical indicators, triglycerides, oxidative status, methylation levels of peroxisomal proliferator-activated receptor alpha (PPARα) gene promoter, expression of PPARα and carnitine palmitoyltransferase 1 (CPT1), and levels of choline metabolites...
November 17, 2016: JPEN. Journal of Parenteral and Enteral Nutrition
Qiang Meng, Xing-Ping Duan, Chang-Yuan Wang, Zhi-Hao Liu, Peng-Yuan Sun, Xiao-Kui Huo, Hui-Jun Sun, Jin-Yong Peng, Ke-Xin Liu
AIM: Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. METHODS: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks...
October 24, 2016: Acta Pharmacologica Sinica
Su Jin Lee, Jeong Han Kang, Da Eun Lee, Min Jeong Nam, Hyun-Shik Lee, Oh-Shin Kwon
Chronic alcohol consumption causes hepatic steatosis, which is characterized by a considerable increase in free fatty acid (FFA) and triglyceride levels. To identify the possible proteins involved in the progression to alcoholic hepatosteatosis, we performed proteomic analysis on livers of mice exposed to alcohol. 2D-based proteomic analysis revealed that EtOH exposure in mice changed the expression of 43 proteins compared with that in mice fed a normal diet (ND). The most notable protein changes were proteins involved in Met metabolism and oxidative stress, most of which were significantly downregulated in alcohol-exposed animals...
October 20, 2016: Journal of Cellular Biochemistry
Liangjian Lu, Albert Koulman, Clive J Petry, Benjamin Jenkins, Lee Matthews, Ieuan A Hughes, Carlo L Acerini, Ken K Ong, David B Dunger
OBJECTIVE: To investigate the relationship between early second trimester serum lipidomic variation and maternal glycemic traits at 28 weeks and to identify predictive lipid biomarkers for gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: Prospective study of 817 pregnant women (discovery cohort, n = 200; validation cohort, n = 617) who provided an early second trimester serum sample and underwent an oral glucose tolerance test (OGTT) at 28 weeks...
December 2016: Diabetes Care
Andrew M Shearer, Rajashree Rana, Karyn Austin, James D Baleja, Nga Nguyen, Andrew Bohm, Lidija Covic, Athan Kuliopulos
Chronic liver inflammation and fibrosis in nonalcoholic steatohepatitis can lead to cirrhosis and liver failure for which there are currently no approved treatments. Protease-activated receptor-2 (PAR2) is an emerging new target expressed on liver stellate cells and hepatocytes that regulates the response to liver injury and inflammation. Here, we identified a pepducin to block the deleterious actions of PAR2 in promoting liver fibrosis. Non-alcoholic fatty liver disease and early fibrosis were induced by the methionine-choline-deficient diet in mice...
October 28, 2016: Journal of Biological Chemistry
R P F Dullaart, Erwin Garcia, Elias Jeyarajah, Eke G Gruppen, Margery A Connelly
BACKGROUND: The choline metabolite, betaine, plays a role in lipid metabolism, and may predict the development of cardiovascular disease and type 2 diabetes mellitus (T2DM). Phospholipid transfer protein (PLTP) and lecithin:cholesterol acyltransferase (LCAT) require phosphatidylcholine as substrate, raising the possibility that there is an intricate relationship of these protein factors with choline metabolism. Here we determined the relationships of PLTP and LCAT activity with betaine in subjects with and without T2DM...
2016: Lipids in Health and Disease
Dongyu Li, Daoyuan Ren, Yiyang Luo, Xingbin Yang
This study was designed to investigate the preventive effect of ursolic acid (UA), a plant-based pentacyclic triterpenoid carboxyl acid, against vascular endothelial damage and liver oxidative injury in the mice fed with 3% dietary high choline (HC) water. Mice fed 3% HC water for 8 weeks significantly displayed liver oxidative stress and vascular endothelial dysfunction (p < 0.01). Furthermore, continuous administration of UA at 400 and 800 mg/kg bw in HC-fed mice could significantly inhibit the HC-induced elevation of serum total cholesterol, total triglyceride, low density lipoprotein-cholesterol, endothelin 1 and thromboxane A2 levels as well as alanine aminotransferase and aspartate aminotransferase activities, while the HC-induced decline of serum high density lipoprotein-cholesterol, endothelial nitric oxide synthase, nitric oxide and prostaglandin I2 levels could be markedly elevated following the treatment (p < 0...
October 25, 2016: Chemico-biological Interactions
M A Anwar, P A Vorkas, J Li, K N Adesina-Georgiadis, O M Reslan, J D Raffetto, E J Want, R A Khalil, E Holmes, A H Davies
OBJECTIVE/BACKGROUND: Circumferential stretch on the vein wall has been suggested as a potential etiological factor in the development of varicose veins. However, the influence of vein wall stretch on vein metabolism has not yet been explored. The aim of this study was to investigate the effect of short and prolonged mechanical stretch on vein wall metabolism. METHODS: Circular segments of inferior vena cava from male Sprague-Dawley rats were exposed to normal 0...
October 2016: European Journal of Vascular and Endovascular Surgery
Zhi Luo, Chuan-Chuan Wei, Han-Mei Ye, Hai-Ping Zhao, Yu-Feng Song, Kun Wu
The present experiment was conducted to determine the effect and mechanism of dietary choline levels on growth performance and lipid deposition of yellow catfish Pelteobagrus fulvidraco. Dietary choline was included at three levels of 239.2 (control (without extra choline addition), 1156.4 and 2273.6mg choline per kg diet, respectively) and fed to yellow catfish (mean initial weight: 3.45±0.02g. mean±standard errors of mean (SEM)) for 8weeks. Fish fed the diet containing 1156.4mgkg(-1) choline showed the higher weight gain (WG), specific growth rate (SGR) and feed intake (FI), but the lower feed conversion rate (FCR), than those in control and highest choline group...
July 27, 2016: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Danhong Long, Tao Gong, Zhirong Zhang, Rui Ding, Yao Fu
A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol...
July 2016: Acta Pharmaceutica Sinica. B
T Wang, D F Chen
OBJECTIVE: To investigate the effect of polyene phosphatidyl choline (PPC) on hepatocyte steatosis and the possible role of the peroxisome proliferators-activated receptor α (PPARα)/carnitine palmityl transferase 1A (CPT-1A) pathway in the treatment. METHODS: L02 hepatocyte steatosis was induced with PPC treatment, and Oil Red O staining and triglyceride measurement were used to evaluate the influence of PPC on the degree of steatosis. Quantitative PCR and Western blot were used to measure the changes in mRNA and protein of CPT-1A, followed by using GW6471 to specifically inhibit the PPARα pathway...
April 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Shuntarou Tsuchiya, Yuichiro Amano, Osamu Isono, Mayumi Imai, Fumi Shimizu, Mari Asada, Shigemitsu Imai, Ayako Harada, Yoshitaka Yasuhara, Ryuichi Tozawa, Hiroshi Nagabukuro
AIM: Low-density lipoprotein receptor knockout (LDLR-KO) mouse fed with modified choline-deficient and amino acid-defined (mCDAA) diet exhibits non-alcoholic steatohepatitis (NASH)-like pathophysiology. In order to pharmacologically benchmark this model, effects of pioglitazone, a thiazolidinedione and candesartan cilexetil, an angiotensin II type 1 receptor blocker (ARB) on steatosis and liver fibrosis were examined. METHODS: Pioglitazone (10 mg/kg) and candesartan cilexetil (3 mg/kg) were orally administered once daily to LDLR-KO mice under mCDAA diet for 7 weeks...
July 15, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Limin Zhang, Prasad Krishnan, David J Ehresman, Philip B Smith, Mainak Dutta, Bradford D Bagley, Shu-Ching Chang, John L Butenhoff, Andrew D Patterson, Jeffrey M Peters
The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress...
September 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Norihiro Kishida, Sachiko Matsuda, Osamu Itano, Masahiro Shinoda, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Taizo Hibi, Yohei Masugi, Koichi Aiura, Michiie Sakamoto, Yuko Kitagawa
BACKGROUND: The incidence of hepatocellular carcinoma with nonalcoholic steatohepatitis is increasing, and its clinicopathological features are well established. Several animal models of nonalcoholic steatohepatitis have been developed to facilitate its study; however, few fully recapitulate all its clinical features, which include insulin resistance, inflammation, fibrosis, and carcinogenesis. Moreover, these models require a relatively long time to produce hepatocellular carcinoma reliably...
2016: BMC Gastroenterology
Yoshimi Nakagawa, Fusaka Oikawa, Seiya Mizuno, Hiroshi Ohno, Yuka Yagishita, Aoi Satoh, Yoshinori Osaki, Kenta Takei, Takuya Kikuchi, Song-Iee Han, Takashi Matsuzaka, Hitoshi Iwasaki, Kazuto Kobayashi, Shigeru Yatoh, Naoya Yahagi, Masaaki Isaka, Hiroaki Suzuki, Hirohito Sone, Satoru Takahashi, Nobuhiro Yamada, Hitoshi Shimano
cAMP responsive element binding protein 3-like 3 (CREB3L3), a transcription factor expressed in the liver and small intestine, governs fasting-response energy homeostasis. Tissue-specific CREB3L3 knockout mice have not been generated till date. To our knowledge, this is the first study using the one-step CRISPR/Cas9 system to generate CREB3L3 floxed mice and subsequently obtain liver- and small intestine-specific Creb3l3 knockout (LKO and IKO, respectively) mice. While LKO mice as well as global KO mice developed hypertriglyceridemia, LKO mice exhibited hypercholesterolemia in contrast to hypocholesterolemia in global KO mice...
2016: Scientific Reports
Dries Bauters, Pieter Spincemaille, Lotte Geys, David Cassiman, Pieter Vermeersch, Pierre Bedossa, Ilse Scroyen, Henri R Lijnen
BACKGROUND & AIMS: Increased prevalence of obesity is paralleled by an increase in non-alcoholic steatohepatitis (NASH). We previously found that the expression of ADAMTS5 (A Disintegrin And Metalloproteinase with Thrombospondin type 1 motifs; member 5) is enhanced in expanding adipose tissue. However, no information is available on a potential role in liver pathology. We studied the effect of ADAMTS5 deficiency on NASH in mice. METHODS: Wild-type (Adamts5(+/+) ) and deficient (Adamts5(-/-) ) mice were kept on a standard- or high-fat diet (HFD) for 15 weeks...
June 2, 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Wei Li, Bo Li, Jiaqi Lv, Li Dong, Lili Zhang, Tian Wang
The objective of this study was to investigate the effects of dietary choline supplementation on hepatic lipid metabolism and gene expression in finishing pigs with intrauterine growth retardation (IUGR). Using a 2 × 2 factorial design, eight normal birth weight (NBW) and eight IUGR weaned pigs were fed either a basal diet (NBW pigs fed a basal diet, NC; IUGR pigs fed a basal diet, IC) or a diet supplemented with two times more choline than the basal diet (NBW pigs fed a high-choline diet, NH; IUGR pigs fed a high-choline diet, IH) until 200 d of age...
May 22, 2016: Asian-Australasian Journal of Animal Sciences
Jiesi Xu, Yang Xu, Yuanyuan Li, Kavita Jadhav, Min You, Liya Yin, Yanqiao Zhang
The liver is a major organ that controls hepatic and systemic homeostasis. Dysregulation of liver metabolism may cause liver injury. Previous studies have demonstrated that carboxylesterase 1 (CES1) regulates hepatic triglyceride metabolism and protects against liver steatosis. In the present study, we investigated whether CES1 played a role in the development of alcoholic liver disease (ALD) and methionine and choline-deficient (MCD) diet-induced liver injury. Both hepatocyte nuclear factor 4α (HNF4α) and CES1 were markedly reduced in patients with alcoholic steatohepatitis...
April 14, 2016: Scientific Reports
Torsten Schröder, David Kucharczyk, Florian Bär, René Pagel, Stefanie Derer, Sebastian Torben Jendrek, Annika Sünderhauf, Ann-Kathrin Brethack, Misa Hirose, Steffen Möller, Axel Künstner, Julia Bischof, Imke Weyers, Jörg Heeren, Dirk Koczan, Sebastian Michael Schmid, Senad Divanovic, Daniel Aaron Giles, Jerzy Adamski, Klaus Fellermann, Hendrik Lehnert, Jörg Köhl, Saleh Ibrahim, Christian Sina
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is associated with an enhanced risk for liver and cardiovascular diseases and mortality. NAFLD can progress from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH). However, the mechanisms predisposing to this progression remain undefined. Notably, hepatic mitochondrial dysfunction is a common finding in patients with NASH. Due to a lack of appropriate experimental animal models, it has not been evaluated whether this mitochondrial dysfunction plays a causative role for the development of NASH...
April 2016: Molecular Metabolism
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