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C E Geisler, C Hepler, M R Higgins, B J Renquist
BACKGROUND: The increased incidence of obesity and associated metabolic diseases has driven research focused on genetically or pharmacologically alleviating metabolic dysfunction. These studies employ a range of fasting-refeeding models including 4-24 h fasts, "overnight" fasts, or meal feeding. Still, we lack literature that describes the physiologically relevant adaptations that accompany changes in the duration of fasting and re-feeding. Since the liver is central to whole body metabolic homeostasis, we investigated the timing of the fast-induced shift toward glycogenolysis, gluconeogenesis, and ketogenesis and the meal-induced switch toward glycogenesis and away from ketogenesis...
2016: Nutrition & Metabolism
Sheo B Singh, Ling Kang, Andrea R Nawrocki, Dan Zhou, Margaret Wu, Stephen Previs, Corey Miller, Haiying Liu, Catherine D G Hines, Maria Madeira, Jin Cao, Kithsiri Herath, Liangsu Wang, David E Kelley, Cai Li, Hong-Ping Guan
OBJECTIVES: Platensimycin (PTM) is a natural antibiotic produced by Streptomyces platensis that selectively inhibits bacterial and mammalian fatty acid synthase (FAS) without affecting synthesis of other lipids. Recently, we reported that oral administration of PTM in mouse models (db/db and db/+) with high de novo lipogenesis (DNL) tone inhibited DNL and enhanced glucose oxidation, which in turn led to net reduction of liver triglycerides (TG), reduced ambient glucose, and improved insulin sensitivity...
2016: PloS One
Theodoros Eleftheriadis, Georgios Pissas, Maria Sounidaki, Konstantina Tsogka, Nikolaos Antoniadis, Georgia Antoniadi, Vassilios Liakopoulos, Ioannis Stefanidis
Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and by degrading L-tryptophan along the kynurenine pathway suppresses CD4+ T-cell proliferation, induces apoptosis and promotes differentiation towards a regulatory as opposed to an effector phenotype. Recent findings revealed that the above effects may be mediated through alterations in T-cell metabolism. In this study, the effect of IDO on fatty acid β-oxidation in CD4+ T-cells was evaluated in human mixed lymphocyte reactions (MLRs) using the IDO inhibitor, 1-DL-methyl-tryptophan...
September 23, 2016: International Journal of Molecular Medicine
Rosa M Pérez-Serrano, M Laura González-Dávalos, Carlos Lozano-Flores, Armando Shimada, Anaid Antaramian, Alfredo Varela-Echavarría, Ofelia Mora
PURPOSE: The aim of this work was to evaluate the effect of PPAR agonists on the differentiation and metabolic features of porcine mesenchymal stem cells induced to the adipogenic or myogenic lineages. METHODS: Bone marrow MSCs from neonate pigs were isolated and identified by cell proliferation, cell surface markers or the gene expression of stem cells (CD44, CD90, CD105 or Oct4 and Nanog, respectively). Cells were differentiated into adipose or muscle cells and treated with the PPAR agonists; adipogenic and myogenic differentiation was promoted by adding these compounds...
September 20, 2016: Cells, Tissues, Organs
Peizhen Xiao, Hong Ji, Yuantu Ye, Baotong Zhang, Yongsheng Chen, Jingjing Tian, Pin Liu, Liqiao Chen, Zhenyu Du
This study was carried out to evaluate whether silymarin supplementation influences growth, lipid metabolism, and health status in grass carp fed elevated dietary lipid levels. The juvenile fish (27.43 ± 0.17 g/tail) were fed six isonitrogenous and isocaloric diets in a factorial design containing 0, 100, or 200 mg kg(-1) silymarin (SM0, SM100, SM200) associated with either 4 or 8 % lipid level (low lipid, LL, and high lipid, HL, respectively) for 82 days. The results showed that both dietary silymarin supplementation and high lipid level significantly enhanced growth performance (WG, SGR), protein efficiency ratio, and feed utilization...
September 8, 2016: Fish Physiology and Biochemistry
Payam Vahmani, William J Meadus, David C Rolland, Pascale Duff, Michael E R Dugan
During ruminal biohydrogenation of α-linolenic acid, a non-conjugated non-methylene interrupted dienoic acid is formed containing a t10 double bond, namely t10,c15-18:2. The present study was designed to examine whether t10,c15-18:2 would exert similar anti-adipogenic effects compared to t10,c12-18:2 in 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated with 35 or 70 µM of LNA, t10,c12-18:2, t10,c15-18:2, or bovine serum albumin (BSA) vehicle control for 120 h. Cellular triacylglycerol and protein were quantified using commercial colorimetric kits...
September 3, 2016: Lipids
Eliska Vavrova, Véronique Lenoir, Marie-Clotilde Alves-Guerra, Raphaël G Denis, Julien Castel, Catherine Esnous, Jason R B Dyck, Serge Luquet, Daniel Metzger, Frédéric Bouillaud, Carina Prip-Buus
Impaired skeletal muscle mitochondrial fatty acid oxidation (mFAO) has been implicated in the etiology of insulin resistance. Carnitine palmitoyltransferase-1 (CPT1) is a key regulatory enzyme of mFAO whose activity is inhibited by malonyl-CoA, a lipogenic intermediate. Whereas increasing CPT1 activity in vitro has been shown to exert a protective effect against lipid-induced insulin resistance in skeletal muscle cells, only a few studies have addressed this issue in vivo. We thus examined whether a direct modulation of muscle CPT1/malonyl-CoA partnership is detrimental or beneficial for insulin sensitivity in the context of diet-induced obesity...
September 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
Monique C de Oliveira, Eduardo H Gilglioni, Bouke A de Boer, Jurgen H Runge, Dirk R de Waart, Clairce L Salgueiro, Emy L Ishii-Iwamoto, Ronald P J Oude Elferink, Ingrid C Gaemers
: Menopause is often followed by obesity and, related to this, non-alcoholic fatty liver disease (NAFLD). Two bile acid (BA) receptors, farnesoid X receptor (FXR) and G-protein-coupled receptor TGR5, have emerged as putative therapeutic targets for obesity and NAFLD. AIM OF THIS STUDY: to evaluate the efficacy of selective agonists INT747/obeticholic acid (FXR) and INT777 (TGR5) as novel treatments for the metabolic effects of oestrogen deficiency. Ovariectomized (OVX) or sham-operated (SHAM) mice were fed a high-fat diet (HFD) for 5weeks...
July 27, 2016: Biochimica et Biophysica Acta
Jae Heon Choi, Sang Woo Kim, Rina Yu, Jong Won Yun
PURPOSE: Appearance of brown-like adipocytes within white adipose tissue depots (browning) is associated with improved metabolic phenotypes, and thus a wide variety of dietary agents that contribute to browning of white adipocytes are being studied. The aim of this study was to assess the browning effect of thymol, a dietary monoterpene phenolic compound, in 3T3-L1 white adipocytes. METHODS: Thymol-induced fat browning was investigated by determining expression levels of brown fat-specific genes and proteins by real-time RT-PCR and immunoblot analysis, respectively...
July 18, 2016: European Journal of Nutrition
Kai Li, Yuzhong Xiao, Junjie Yu, Tingting Xia, Bin Liu, Yajie Guo, Jiali Deng, Shanghai Chen, Chunxia Wang, Feifan Guo
Although numerous biological functions of the activating transcription factor 4 (ATF4) have been identified, a direct effect of ATF4 on alcoholic liver steatosis has not been described previously. The aim of our current study is to investigate the role of ATF4 in alcoholic liver steatosis and elucidate the underlying mechanisms. Here, we showed that the expression of ATF4 is induced by ethanol in hepatocytes in vitro and in vivo, and liver-specific ATF4 knock-out mice are resistant to ethanol-induced liver steatosis, associated with stimulated hepatic AMP-activated protein kinase (AMPK) activity...
August 26, 2016: Journal of Biological Chemistry
Y Zhang, F Guo, R Zhao
The fat mass and obesity associated (FTO) gene, which encodes a demethylase of m(6)A, has been reported to respond to lipopolysaccharide (LPS) and to serve as a link between inflammation and metabolic responses. The objective of this study was to determine whether LPS-induced changes in the expression of FTO and metabolic genes are associated with alterations of m(6)A in relevant mRNAs. LPS challenge significantly decreased hepatic mRNA expression of carnitine palmitoyl transferase 1 (CPT1) and CPT2, which coincided with a tendency of higher triglyceride accumulation in the liver...
October 2016: British Poultry Science
Laurence Britton, Lesley Jaskowski, Kim Bridle, Nishreen Santrampurwala, Janske Reiling, Nick Musgrave, V Nathan Subramaniam, Darrell Crawford
Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight-week-old wild-type and Hfe(+/-) mice received 8 weeks of a control diet or HCD Liver histology and pathways of lipid and iron metabolism were analyzed...
June 2016: Physiological Reports
Shigeo Shinohara, Yuanjun Gu, Ying Yang, Yasuo Furuta, Masahiko Tanaka, Xiaohua Yue, Weiqing Wang, Masaru Kitano, Hiroshi Kimura
Desi-type chickpeas, which have long been used as a natural treatment for diabetes, have been reported to lower visceral adiposity, dyslipidemia and insulin resistance induced by a chronic high-fat diet in rats. In this study, in order to examine the effects of chickpeas of this type in an in vitro system, we used the 3T3-L1 mouse cell line, a subclone of Swiss 3T3 cells, which can differentiate into cells with an adipocyte-like phenotype, and we used ethanol extracts of chickpeas (ECP) instead of chickpeas...
August 2016: International Journal of Molecular Medicine
Ana Luisa Gavito, Dolores Bautista, Juan Suarez, Samir Badran, Rocío Arco, Francisco Javier Pavón, Antonia Serrano, Patricia Rivera, Juan Decara, Antonio Luis Cuesta, Fernando Rodríguez-de-Fonseca, Elena Baixeras
High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. IL-6 administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of fatty liver disease, high doses of human IL-6 ameliorate the liver steatosis, whereas restoration of IL-6 in DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes and aggravates steatosis. We further examined the effects of chronic low doses of murine IL-6 on hepatic lipid metabolism in WT mice in DIO...
2016: PloS One
Kelly M Hammond, Samuel G Impey, Kevin Currell, Nigel Mitchell, Sam O Shepherd, Stewart Jeromson, John A Hawley, Graeme L Close, D Lee Hamilton, Adam P Sharples, James P Morton
PURPOSE: To examine the effects of reduced CHO but high post-exercise fat availability on cell signalling and expression of genes with putative roles in regulation of mitochondrial biogenesis, lipid metabolism and muscle protein synthesis (MPS). METHODS: Ten males completed a twice per day exercise model (3.5 h between sessions) comprising morning high-intensity interval (HIT) (8 x 5-min at 85% VO2peak) and afternoon steady-state (SS) running (60 min at 70% VO2peak)...
June 20, 2016: Medicine and Science in Sports and Exercise
Paula Fernandes Aguiar, Sílvia Mourão Magalhães, Ivana Alice Teixeira Fonseca, Vanessa Batista da Costa Santos, Mariana Aguiar de Matos, Marco Fabrício Dias Peixoto, Fábio Yuzo Nakamura, Craig Crandall, Hygor Nunes Araújo, Leonardo Reis Silveira, Etel Rocha-Vieira, Flávio de Castro Magalhães, Fabiano Trigueiro Amorim
This study aims to evaluate the effect of regular post-exercise cold water immersion (CWI) on intramuscular markers of cellular stress response and signaling molecules related to mitochondria biogenesis and exercise performance after 4 weeks of high intensity interval training (HIIT). Seventeen healthy subjects were allocated into two groups: control (CON, n = 9) or CWI (n = 8). Each HIIT session consisted of 8-12 cycling exercise stimuli (90-110 % of peak power) for 60 s followed by 75 s of active recovery three times per week, for 4 weeks (12 HIIT sessions)...
September 2016: Cell Stress & Chaperones
Xiaochen Yuan, Xu-Fang Liang, Liwei Liu, Jinguang Fang, Jiao Li, Aixuan Li, Wenjing Cai, Min Xue, Jia Wang, Qingchao Wang
This study aimed to evaluate the fat deposition pattern and lipid metabolic strategies of grass carp in response to dietary lipid levels. Five isonitrogenous diets (260 g kg(-1) crude protein) containing five dietary lipid levels (0, 20, 40, 60, 80 g kg(-1)) were fed to quadruplicate groups of 15 fish with initial weight 200 g, for 8 weeks. The best growth performance and feed utilization was observed in fish fed with lipid level at 40 g kg(-1). MFI and adipose tissue lipid content increased with increasing dietary lipid level up to 40 g kg(-1), and higher lipid level in diet made no sense...
May 23, 2016: Fish Physiology and Biochemistry
Xuqing Chen, Feifei Zhang, Qi Gong, Aoyuan Cui, Shu Zhuo, Zhimin Hu, Yamei Han, Jing Gao, Yixuan Sun, Zhengshuai Liu, Zhongnan Yang, Yingying Le, Xianfu Gao, Lily Q Dong, Xin Gao, Yu Li
The endoplasmic reticulum quality control protein activating transcription factor 6 (ATF6) has emerged as a novel metabolic regulator. Here, we show that adenovirus-mediated overexpression of the dominant-negative form of ATF6 (dnATF6) increases susceptibility to develop hepatic steatosis in diet-induced insulin-resistant mice and fasted mice. Overexpression of dnATF6 or small interfering RNA-mediated knockdown of ATF6 decreases the transcriptional activity of peroxisome proliferator-activated receptor α (PPARα)/retinoid X receptor complex, and inhibits oxygen consumption rates in hepatocytes, possibly through inhibition of the binding of PPARα to the promoter of its target gene...
July 2016: Diabetes
Junqin Chen, Martin E Young, John C Chatham, David K Crossman, Louis J Dell'Italia, Anath Shalev
Myocardial fatty acid β-oxidation is critical for the maintenance of energy homeostasis and contractile function in the heart, but its regulation is still not fully understood. While thioredoxin-interacting protein (TXNIP) has recently been implicated in cardiac metabolism and mitochondrial function, its effects on β-oxidation have remained unexplored. Using a new cardiomyocyte-specific TXNIP knockout mouse and working heart perfusion studies, as well as loss- and gain-of-function experiments in rat H9C2 and human AC16 cardiomyocytes, we discovered that TXNIP deficiency promotes myocardial β-oxidation via signaling through a specific microRNA, miR-33a...
July 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
Adam Prostek, Małgorzata Gajewska, Bożena Bałasińska
Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are n-3 long chain polyunsaturated fatty acids. The purpose of our study was to evaluate the influence of EPA and DHA on expression of genes connected with metabolism and secretory functions of ageing adipocytes. Young, mature and old differentiated 3T3-L1 adipocytes were cultured for 48h in the presence of EPA, or DHA. Both fatty acids increased the expression of Pparg, FATP1, FATP4 and ATGL genes, but only in young 3T3-L1 adipocytes. Moreover, in young, mature and old cells DHA elevated the expression of CPT1 gene...
September 2016: Prostaglandins & Other Lipid Mediators
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