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https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#1
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28915573/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#2
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28895586/maresin-1-mitigates-liver-steatosis-in-ob-ob-and-diet-induced-obese-mice
#3
L M Laiglesia, S Lorente-Cebrián, L Martínez-Fernández, N Sáinz, P L Prieto-Hontoria, M A Burrell, C M Rodríguez-Ortigosa, J A Martínez, M J Moreno-Aliaga
BACKGROUND/OBJECTIVES: The aim of this study was to characterize the effects of Maresin 1 (MaR1) in obesity-related liver steatosis and the mechanisms involved. METHODS: MaR1 effects on fatty liver disease were tested in ob/ob (2-10 μg/kg i.p., 20 days) and in diet-induced obese (DIO) mice (2 μg/kg, i.p., or 50 μg/kg, oral gavage for 10 days), as well as in cultured hepatocytes. RESULTS: In ob/ob mice, MaR1 reduced liver triglycerides (TG) content, fatty acid synthase (FAS) and stearoyl-CoA desaturase-1 protein expression, while increased acetyl-CoA carboxylase (ACC) phosphorylation and LC3II protein expression, in parallel with a drop in p62 levels...
September 12, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28891024/resveratrol-supplementation-improves-lipid-and-glucose-metabolism-in-high-fat-diet-fed-blunt-snout-bream
#4
Dingdong Zhang, Yanan Yan, Hongyan Tian, Guangzhen Jiang, Xiangfei Li, Wenbin Liu
Here, we aimed to investigate whether resveratrol (RSV) can ameliorate high-fat diet (HFD)-induced metabolic disorder in fish. Blunt snout bream (Megalobrama amblycephala) with average weight 27.99 ± 0.56 g were fed a normal fat diet (NFD, 5% fat, w/w), a HFD (11% fat), or a HFD supplemented with 0.04, 0.36, or 1.08% RSV for 10 weeks. As expected, fish fed a HFD developed hepatic steatosis, as shown by elevated hepatic and plasma triglycerides, raised whole body fat, intraperitoneal fat ratio and hepatosomatic index, and increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST)...
September 10, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28865848/grain-challenge-affects-systemic-and-hepatic-molecular-biomarkers-of-inflammation-stress-and-metabolic-responses-to-a-greater-extent-in-holstein-than-jersey-cows
#5
T Xu, F C Cardoso, A Pineda, E Trevisi, X Shen, F Rosa, J S Osorio, J J Loor
Long-term feeding of high-grain diets to dairy cows often results in systemic inflammation characterized by alterations in acute-phase proteins and other biomarkers, both in plasma and immune-responsive tissues like the liver. The molecular and systemic changes that characterize an acute grain feeding challenge remain unclear. The current study involved 6 Holstein and 6 Jersey cows in a replicated 2 × 2 Latin square. Periods (10 d) were divided into 4 stages (S): S1, d 1 to 3, served as baseline with total mixed ration (TMR) ad libitum; S2, d 4, served as restricted feeding, with cows offered 50% of the average daily intake observed in S1; S3, d 5, a grain challenge was performed, in which cows were fed a TMR ad libitum without (CON) or with an additional pellet wheat-barley (1:1; HIG) at 20% of dry matter intake top-dressed onto the TMR; S4, d 6 to 10, served as recovery during which cows were allowed ad libitum access to the TMR...
August 30, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28854364/a-fatty-acid-oxidation-dependent-metabolic-shift-regulates-adult-neural-stem-cell-activity
#6
Marlen Knobloch, Gregor-Alexander Pilz, Bart Ghesquière, Werner J Kovacs, Thomas Wegleiter, Darcie L Moore, Martina Hruzova, Nicola Zamboni, Peter Carmeliet, Sebastian Jessberger
Hippocampal neurogenesis is important for certain forms of cognition, and failing neurogenesis has been implicated in neuropsychiatric diseases. The neurogenic capacity of hippocampal neural stem/progenitor cells (NSPCs) depends on a balance between quiescent and proliferative states. Here, we show that the rate of fatty acid oxidation (FAO) regulates the activity of NSPCs. Quiescent NSPCs show high levels of carnitine palmitoyltransferase 1a (Cpt1a)-dependent FAO, which is downregulated in proliferating NSPCs...
August 29, 2017: Cell Reports
https://www.readbyqxmd.com/read/28843495/high-intensity-interval-versus-moderate-intensity-continuous-training-superior-metabolic-benefits-in-diet-induced-obesity-mice
#7
Ningning Wang, Yang Liu, Yanan Ma, Deliang Wen
AIMS: Exercise is beneficial in obesity, however, the debate about the value of high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MICT) has been long lasting. Therefore, here we have compared the possible beneficial effects of two different exercise training regimes in a mouse model of diet-induced obesity (DIO). MATERIALS AND METHODS: Following 7wk. on high fat diet (HFD), ten-week-old male ICR mice (n=30) were assigned to HIIT, distance-matched MICT or remained sedentary for the next 8 constitutive weeks while maintaining the dietary treatments...
August 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28771253/health-effects-of-the-cpt1a-p479l-variant-responsible-public-health-policy
#8
David M Koeller, Matt Hirschfeld, Stephanie Birch, Thalia Wood, Rebekah Morisse, Sabra Anckner, Bradford D Gessner
No abstract text is available yet for this article.
August 3, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28748224/utility-of-genetic-testing-for-confirmation-of-abnormal-newborn-screening-in-disorders-of-long-chain-fatty-acids-a-missed-case-of-carnitine-palmitoyltransferase-1a-cpt1a-deficiency
#9
Leah Dowsett, Lauren Lulis, Can Ficicioglu, Sanmati Cuddapah
An 18-month-old male was evaluated after presenting with disproportionately elevated liver transaminases in the setting of acute gastroenteritis. He had marked hepatomegaly on physical exam that was later confirmed with an abdominal ultrasound. Given this clinical picture, suspicion for a fatty acid oxidation disorder was raised. Further investigation revealed that his initial newborn screen was positive for carnitine palmitoyltransferase 1A (CPT1A) deficiency-a rare autosomal recessive disorder of long-chain fatty acid oxidation...
June 2017: International Journal of Neonatal Screening
https://www.readbyqxmd.com/read/28744221/sexual-dimorphism-in-the-age-induced-insulin-resistance-liver-steatosis-and-adipose-tissue-function-in-rats
#10
Francisco Garcia-Carrizo, Teresa Priego, Nara Szostaczuk, Andreu Palou, Catalina Picó
Age-linked metabolic disturbances, such as liver steatosis and insulin resistance, show greater prevalence in men than in women. Thus, our aim was to analyze these sex-related differences in male and female Wistar rats (aged 26 days and 3, 7, and 14 months), and to assess their potential relationship with alterations in the capacity of adipose tissue expansion and the dysregulation of the main adipokines produced by the adipose tissue, leptin and adiponectin. Adiposity-related parameters, blood parameters, the expression of genes related to expandability and inflammation (WAT), lipid metabolism (liver), and leptin and insulin signaling (both tissues) were measured...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28722145/dendrobium-nobile-lindl-alkaloids-regulate-metabolism-gene-expression-in-livers-of-mice
#11
Yun-Yan Xu, Ya-Sha Xu, Yuan Wang, Qin Wu, Yuan-Fu Lu, Jie Liu, Jing-Shan Shi
OBJECTIVES: In our previous studies, Dendrobium nobile Lindl. alkaloids (DNLA) has been shown to have glucose-lowering and antihyperlipidaemia effects in diabetic rats, in rats fed with high-fat diets, and in mice challenged with adrenaline. This study aimed to examine the effects of DNLA on the expression of glucose and lipid metabolism genes in livers of mice. METHODS: Mice were given DNLA at doses of 10-80 mg/kg, po for 8 days, and livers were removed for total RNA and protein isolation to perform real-time RT-PCR and Western blot analysis...
July 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28706492/lower-expression-of-slc27a1-enhances-intramuscular-fat-deposition-in-chicken-via-down-regulated-fatty-acid-oxidation-mediated-by-cpt1a
#12
Fengfang Qiu, Liang Xie, Jing-E Ma, Wen Luo, Li Zhang, Zhe Chao, Shaohao Chen, Qinghua Nie, Zhemin Lin, Xiquan Zhang
Intramuscular fat (IMF) is recognized as the predominant factor affecting meat quality due to its positive correlation with tenderness, juiciness, and flavor. Chicken IMF deposition depends on the balance among lipid synthesis, transport, uptake, and subsequent metabolism, involving a lot of genes and pathways, however, its precise molecular mechanisms remain poorly understood. In the present study, the breast muscle tissue of female Wenchang chickens (WC) (higher IMF content, 1.24 in D120 and 1.62 in D180) and female White Recessive Rock chickens (WRR; lower IMF content, 0...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28706214/transcriptome-analysis-of-three-sheep-intestinal-regions-reveals-key-pathways-and-hub-regulatory-genes-of-large-intestinal-lipid-metabolism
#13
Tianle Chao, Guizhi Wang, Zhibin Ji, Zhaohua Liu, Lei Hou, Jin Wang, Jianmin Wang
The large intestine, also known as the hindgut, is an important part of the animal digestive system. Recent studies on digestive system development in ruminants have focused on the rumen and the small intestine, but the molecular mechanisms underlying sheep large intestine metabolism remain poorly understood. To identify genes related to intestinal metabolism and to reveal molecular regulation mechanisms, we sequenced and compared the transcriptomes of mucosal epithelial tissues among the cecum, proximal colon and duodenum...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696376/lack-of-additive-effects-of-resveratrol-and-energy-restriction-in-the-treatment-of-hepatic-steatosis-in-rats
#14
Iñaki Milton-Laskibar, Leixuri Aguirre, Alfredo Fernández-Quintela, Anabela P Rolo, João Soeiro Teodoro, Carlos M Palmeira, María P Portillo
The aims of the present study were to analyze the effect of resveratrol on liver steatosis in obese rats, to compare the effects induced by resveratrol and energy restriction and to research potential additive effects. Rats were initially fed a high-fat high-sucrose diet for six weeks and then allocated in four experimental groups fed a standard diet: a control group, a resveratrol-treated group, an energy restricted group and a group submitted to energy restriction and treated with resveratrol. We measured liver triacylglycerols, transaminases, FAS, MTP, CPT1a, CS, COX, SDH and ATP synthase activities, FATP2/FATP5, DGAT2, PPARα, SIRT1, UCP2 protein expressions, ACC and AMPK phosphorylation and PGC1α deacetylation...
July 11, 2017: Nutrients
https://www.readbyqxmd.com/read/28671672/deregulation-of-micrornas-mediated-control-of-carnitine-cycle-in-prostate-cancer-molecular-basis-and-pathophysiological-consequences
#15
A Valentino, A Calarco, A Di Salle, M Finicelli, S Crispi, R A Calogero, F Riccardo, A Sciarra, A Gentilucci, U Galderisi, S Margarucci, G Peluso
Cancer cells reprogram their metabolism to maintain both viability and uncontrolled proliferation. Although an interplay between the genetic, epigenetic and metabolic rewiring in cancer is beginning to emerge, it remains unclear how this metabolic plasticity occurs. Here, we report that in prostate cancer cells (PCCs) microRNAs (miRNAs) greatly contribute to deregulation of mitochondrial fatty acid (FA) oxidation via carnitine system modulation. We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells...
July 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28647730/qiliqiangxin-attenuates-adverse-cardiac-remodeling-after-myocardial-infarction-in-ovariectomized-mice-via-activation-of-ppar%C3%AE
#16
Shutong Shen, Huimin Jiang, Yihua Bei, Jialiang Zhang, Haifeng Zhang, Hongsheng Zhu, Chenlin Zhang, Wenming Yao, Cong Wei, Hongcai Shang, Xinli Li
BACKGROUND/AIMS: This study was designed to investigate the therapeutic effect of traditional Chinese medication Qiliqiangxin (QLQX) on adverse cardiac remodeling after myocardial infarction (MI) in bilateral ovariectomized (OVX) female mice. METHODS: Eight-week old female C57BL/6 mice were operated to ligate the left anterior descending coronary artery seven days after bilateral ovariectomy and were orally administered either QLQX or vehicle. 21 days after ligation, echocardiography was performed to evaluate the heart function of all mice...
June 23, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28636830/attenuation-of-hepatic-steatosis-by-purple-sweet-potato-colour-is-associated-with-blocking-src-erk-c-ebp%C3%AE-signalling-in-high-fat-diet-treated-mice
#17
Xin Wang, Zi-Feng Zhang, Gui-Hong Zheng, Ai-Min Wang, Chun-Hui Sun, Su-Ping Qin, Juan Zhuang, Jun Lu, Dai-Fu Ma, Yuan-Lin Zheng
Our previous work showed that purple sweet potato colour (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat-diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into 4 groups: control group, HFD group, HFD+PSPC group, and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/(kg·day)(-1)). Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice...
June 21, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28611031/cpt1a-missense-mutation-associated-with-fatty-acid-metabolism-and-reduced-height-in-greenlanders
#18
Line Skotte, Anders Koch, Victor Yakimov, Sirui Zhou, Bolette Søborg, Mikael Andersson, Sascha W Michelsen, Johan E Navne, Jacqueline M Mistry, Patrick A Dion, Michael L Pedersen, Malene L Børresen, Guy A Rouleau, Frank Geller, Mads Melbye, Bjarke Feenstra
BACKGROUND: Inuit have lived for thousands of years in an extremely cold environment on a diet dominated by marine-derived fat. To investigate how this selective pressure has affected the genetic regulation of fatty acid metabolism, we assessed 233 serum metabolic phenotypes in a population-based sample of 1570 Greenlanders. METHODS AND RESULTS: Using array-based and targeted genotyping, we found that rs80356779, a p.Pro479Leu variant in CPT1A, was strongly associated with markers of n-3 fatty acid metabolism, including degree of unsaturation (P=1...
June 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28587208/xyloketal-b-attenuates-fatty-acid-induced-lipid-accumulation-via-the-srebp-1c-pathway-in-nafld-models
#19
Youying Zhang, Tian Meng, Ling Zuo, Yu Bei, Qihao Zhang, Zhijian Su, Yadong Huang, Jiyan Pang, Qi Xiang, Hongtu Yang
The goal of this study was to examine the effects of xyloketal B on nonalcoholic fatty liver disease (NAFLD) and to explore the molecular mechanisms underlying its effects in both in vivo and in vitro models. We discovered an association between xyloketal B and the sterol regulatory element-binding protein-1c (SREBP-1c) signaling pathway, which is related to lipid metabolism. Mice were dosed with xyloketal B (5, 10 and 20 mg/kg/d) and atorvastatin (15 mg/kg/d) via intraperitoneal injection once daily for 40 days after being fed a high fat diet plus 10% high fructose liquid (HFD+HFL) for 8 weeks...
June 3, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28580300/resveratrol-attenuates-triglyceride-accumulation-associated-with-upregulation-of-sirt1-and-lipoprotein-lipase-in-3t3-l1-adipocytes
#20
Haruki Imamura, Daiji Nagayama, Noriko Ishihara, Syo Tanaka, Rena Watanabe, Yasuhiro Watanabe, Yuta Sato, Takashi Yamaguchi, Noriko Ban, Hidetoshi Kawana, Masahiro Ohira, Kei Endo, Atsuhito Saiki, Kohji Shirai, Ichiro Tatsuno
AIM: We aimed to investigate the effect of resveratrol (Rsv) on expression of genes regulating triglyceride (TG) accumulation and consumption in differentiated 3T3-L1 preadipocytes. METHODS: 3T3-L1 preadipocytes were cultured in DMEM supplemented with 10% fetal calf serum. Upon reaching confluence, cells were induced to differentiate for 4 days, cultured for 10 days for TG accumulation, and then incubated with Rsv (0, 25 or 50 μM) for 3 days. TG accumulation was analyzed by Oil Red-O staining...
September 2017: Molecular Genetics and Metabolism Reports
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