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ampk regulation of fatty acids

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https://www.readbyqxmd.com/read/29656110/targeting-hepatic-pyruvate-dehydrogenase-kinases-restores-insulin-signaling-and-mitigates-chrebp-mediated-lipogenesis-in-diet-induced-obese-mice
#1
Cheng-Yang Wu, Shih-Chia Tso, Jacinta L Chuang, Wen-Jun Gui, Mingliang Lou, Gaurav Sharma, Chalermchai Khemtong, Xiangbing Qi, R Max Wynn, David T Chuang
OBJECTIVE: Mitochondrial pyruvate dehydrogenase kinases 1-4 (PDKs1-4) negatively regulate activity of the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation. PDKs play a pivotal role in maintaining energy homeostasis and contribute to metabolic flexibility by attenuating PDC activity in various mammalian tissues. Cumulative evidence has shown that the up-regulation of PDK4 expression is tightly associated with obesity and diabetes. In this investigation, we test the central hypothesis that PDKs1-4 are a pharmacological target for lowering glucose levels and restoring insulin sensitivity in obesity and type 2 diabetes (T2D)...
March 31, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29614883/bergamottin-inhibits-adipogenesis-in-3t3-l1-cells-and-weight-regulation-in-diet-induced-obese-mice
#2
Jeong-Hyeon Ko, Dongwoo Nam, Jae-Young Um, Sang Hoon Jung, Kwang Seok Ahn
Obesity is a serious and increasing health problem worldwide, and the inhibition of adipogenesis is considered to be a potential therapeutic target for it. Bergamottin (BGM), a component of grapefruit juice, has been reported to regulate lipolysis. However, the physiological role of BGM in obesity has not been evaluated so far. In the present study, we investigated the effects of BGM on obesity in 3T3-L1 cells and in mice fed a high-fat diet (HFD). BGM inhibited adipogenic differentiation of 3T3-L1 cells along with a significant decrease in the lipid content by downregulating the expression of two critical adipogenic factors, CCAAT enhancer-binding protein-alpha (C/EBP[Formula: see text]) and peroxisome proliferator activated receptor-gamma (PPAR[Formula: see text])...
April 4, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29593575/dai-zong-fang-a-traditional-chinese-herbal-formula-ameliorates-insulin-resistance-in-db-db-mice
#3
Lili Zhu, Xiaoyun Zhu, Guibo Sun, Xiangbao Meng, Min Wang, Hanming Cui, Jialong Wang, Yadong Zhai, Ke Yang, Yang Tang, Xiaobo Sun, Ximing Liu
Intricate health problems, such as insulin resistance (IR) and its associated diseases, call for multi-targeted therapies with few side effects. Based on traditional Chinese medicine (TCM), Dai-Zong-Fang (DZF) is an herbal formula mainly composed of Rhizoma Coptidis (Huanglian) and Fructus Aurantii Immaturus (Zhishi), of which berberine and naringin are the main constituents. Though DZF has been clinically used for treatment of IR and metabolic syndrome for decades, its mechanism in vivo remains unknown. In the present study, we observed that both DZF and metformin, the first-line drug for type 2 diabetes, ameliorated insulin resistance with significant improvement of oral glucose tolerance test (OGTT) and homeostasis model assessment of IR (HOMA-IR) level in diabetic C57BL/Ksj-Lepr db -/- ( db/db ) mice...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29574225/dioscin-alleviates-non-alcoholic-fatty-liver-disease-through-adjusting-lipid-metabolism-via-sirt1-ampk-signaling-pathway
#4
Hong Yao, Xufeng Tao, Lina Xu, Yan Qi, Lianhong Yin, Xu Han, Youwei Xu, Lingli Zheng, Jinyong Peng
Dioscin, one natural product, has active effect against non-alcoholic fatty liver disease (NAFLD) in our previous work. However, the pharmacological data are insufficient and the mechanisms have not been reported. Thus, this study aims to comprehensively investigate the effects and molecular mechanisms of dioscin against NAFLD. The primary cultured hepatocytes, AML-12 and HepG-2 cells were treated with palmic acid (PA) after dioscin treatment. The mice and rats were induced by high fat diet to establish the in vivo models of NAFLD...
March 21, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29571766/dehydroepiandrosterone-reduces-accumulation-of-lipid-droplets-in-primary-chicken-hepatocytes-by-biotransformation-mediated-via-the-camp-pka-erk1-2-signaling-pathway
#5
Longlong Li, Chongyang Ge, Dian Wang, Lei Yu, Jinlong Zhao, Haitian Ma
Dehydroepiandrosterone (DHEA) is commonly used as a nutritional supplement to control fat deposition, but the mechanism of this action is poorly understood. In this study, we demonstrated that DHEA increased phosphorylation of AMP-activated protein kinase (p-AMPK). Elevated p-AMPK levels resulted in reduced expression of sterol regulatory element binding protein-1c, acetyl CoA carboxylase, fatty acid synthase and enhanced expression of peroxisome proliferators-activated receptor α and carnitine palmitoyl transferase-I, ultimately leading to the reduction of lipid droplet accumulation in primary chicken hepatocytes...
March 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29570858/metabolic-control-of-cell-fate-bifurcations-in-a-hematopoietic-progenitor-population
#6
Radomir Kratchmarov, Sara Viragova, Min Jung Kim, Nyanza J Rothman, Kang Liu, Boris Reizis, Steven L Reiner
Growth signals drive hematopoietic progenitor cells to proliferate and branch into divergent cell fates, but how unequal outcomes arise from a common progenitor is not fully understood. We used steady-state analysis of in vivo hematopoiesis and Fms-related tyrosine kinase 3 ligand (Flt3L)-induced in vitro differentiation of dendritic cells (DCs) to determine how growth signals regulate lineage bias. We found that Flt3L signaling induced anabolic activation and proliferation of DC progenitors, which was associated with DC differentiation...
March 23, 2018: Immunology and Cell Biology
https://www.readbyqxmd.com/read/29563875/mangiferin-improves-hepatic-lipid-metabolism-mainly-through-its-metabolite-norathyriol-by-modulating-sirt-1-ampk-srebp-1c-signaling
#7
Jian Li, Mengyang Liu, Haiyang Yu, Wei Wang, Lifeng Han, Qian Chen, Jingya Ruan, Shaoshi Wen, Yi Zhang, Tao Wang
Objective: Mangiferin (MGF) is a natural xanthone, with regulation effect on lipid metabolism. However, the molecular mechanism remains unclear. We purposed after oral administration, MGF is converted to its active metabolite(s), which contributes to the effects on lipid metabolism. Methods: KK-Ay mice were used to validate the effects of MGF on lipid metabolic disorders. Liver biochemical indices and gene expressions were determined. MGF metabolites were isolated from MGF administrated rat urine. Mechanism studies were carried out using HepG2 cells treated by MGF and its metabolite with or without inhibitors or small interfering RNA (siRNA)...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29547798/magnolol-promotes-thermogenesis-and-attenuates-oxidative-stress-in-3t3-l1-adipocytes
#8
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
https://www.readbyqxmd.com/read/29542003/scutellaria-baicalensis-regulates-ffa-metabolism-to-ameliorate-nafld-through-the-ampk-mediated-srebp-signaling-pathway
#9
Qian Chen, Mengyang Liu, Haiyang Yu, Jian Li, Sijian Wang, Yi Zhang, Feng Qiu, Tao Wang
Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Ay mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA...
March 14, 2018: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29525316/trans-10-cis-12-conjugated-linoleic-acid-alters-lipid-metabolism-of-goat-mammary-epithelial-cells-by-regulation-of-de-novo-synthesis-and-the-ampk-signaling-pathway
#10
T Y Zhang, J T Huang, H B Tian, Y Ma, Z Chen, J J Wang, H P Shi, J Luo
The trans-10,cis-12 isomer of conjugated linoleic acid (t10c12-CLA) is a biohydrogenation intermediate in the rumen and has been shown to cause milk fat depression in dairy goats. However, few studies have focused on the in vitro molecular mechanisms involved in the response of the goat mammary gland to t10c12-CLA. In the present study, RNA sequencing technology was used to investigate the effects of t10c12-CLA on goat mammary epithelial cells. From the data, 25,153 annotated transcripts were obtained, and differentially expressed genes were selected based on a false discovery rate <0...
March 7, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29518607/pedunculoside-a-novel-triterpene-saponin-extracted-from-ilex-rotunda-ameliorates-high-fat-diet-induced-hyperlipidemia-in-rats
#11
Chang Liu, Yan-Jun Shen, Qing-Bo Tu, Yan-Ran Zhao, Hao Guo, Juan Wang, Li Zhang, Hua-Wei Shi, Yun Sun
Pedunculoside (PE) is a novel triterpene saponin extracted from the dried barks of Ilex rotunda Thunb. The present study aims to explore lipid-lowering effects of PE on hyperlipidemia rat induced by high-fat diet. The rats were fed with the high-fat diet and subjected to intragastric administration of PE at doses of 30, 15, or 5 mg/kg daily for 7 weeks. The results demonstrated that treatment with PE for 7-week dramatically decreased serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and reduced liver TC in hyperlipidemia rat induced by high-fat diet...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29507591/-zanthoxylum-ailanthoides-suppresses-oleic-acid-induced-lipid-accumulation-through-an-activation-of-lkb1-ampk-pathway-in-hepg2-cells
#12
Eun-Bin Kwon, Myung-Ji Kang, Soo-Yeon Kim, Yong-Moon Lee, Mi-Kyeong Lee, Heung Joo Yuk, Hyung Won Ryu, Su Ui Lee, Sei-Ryang Oh, Dong-Oh Moon, Hyun-Sun Lee, Mun-Ock Kim
Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29504286/cold-acclimation-reduces-hepatic-protein-kinase-b-and-amp-activated-protein-kinase-phosphorylation-and-increases-gluconeogenesis-in-rats
#13
Diane M Sepa-Kishi, Glen Katsnelson, George Bikopoulos, Ayesha Iqbal, Rolando B Ceddia
This study investigated the molecular and metabolic responses of the liver to cold-induced thermogenesis. To accomplish that, male Wistar rats were exposed to cold (4°C) for 7 days. Livers were then extracted and used for the determination of glucose and fatty acid oxidation, glycogen content, the expression and content of proteins involved in insulin signaling, as well as in the regulation of gluconeogenesis and de novo lipid synthesis. Despite being hyperphagic, cold-acclimated rats displayed normoglycemia with reduced insulinemia, which suggests improved whole-body insulin sensitivity...
March 2018: Physiological Reports
https://www.readbyqxmd.com/read/29480487/measurement-of-ampk-induced-inhibition-of-lipid-synthesis-flux-in-cultured-cells
#14
Marc Foretz, Benoit Viollet
AMP-activated protein kinase (AMPK) is a master regulator of multiple cellular metabolic pathways, including lipid metabolism. Some of the well-known substrates of AMPK are acetyl-CoA carboxylase (ACC) and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, regulatory enzymes of fatty acid and cholesterol synthesis, respectively. The discovery that both of them are inactivated by AMPK suggested the therapeutic potential of AMPK activation in the treatment of metabolic diseases associated with lipid disorders, such as nonalcoholic fatty liver disease (NAFLD)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29480486/assessment-of-ampk-stimulated-cellular-long-chain-fatty-acid-and-glucose-uptake
#15
Joost J F P Luiken, Dietbert Neumann, Jan F C Glatz, Will A Coumans, Dipanjan Chanda, Miranda Nabben
Here we describe an assay for simultaneous measurement of cellular uptake rates of long-chain fatty acids (LCFA) and glucose that can be applied to cells in suspension. The uptake assay includes the use of radiolabeled substrates at such concentrations and incubation periods that exact information is provided about unidirectional uptakes rates. Cellular uptake of both substrates is under regulation of AMPK. The underlying mechanism includes the translocation of LCFA and glucose transporters from intracellular membrane compartments to the cell surface, leading to an increase in substrate uptake...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29468762/hypolipidemic-activity-and-mechanisms-of-the-total-phenylpropanoid-glycosides-from-ligustrum-robustum-roxb-blume-by-ampk-srebp-1c-pathway-in-hamsters-fed-a-high-fat-diet
#16
Runmei Yang, Xinxin Chu, Le Sun, Zhuoying Kang, Min Ji, Ying Yu, Ying Liu, Zhendan He, Nannan Gao
The aim of this study was to evaluate the hypolipidemic effect and mechanisms of total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) in hamsters fed a high-fat diet and to discover bioactive components in HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6 g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days in hamsters. We found that in hamsters fed a high-fat diet, LRTPG effectively reduced the concentrations of plasma triglycerides (TG), free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and hepatic TG and total cholesterol...
February 22, 2018: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/29447962/low-molecular-weight-fucoidan-attenuates-liver-injury-via-sirt1-ampk-pgc1%C3%AE-axis-in-db-db-mice
#17
Yuanyuan Zheng, Tiantian Liu, Zhiqiang Wang, Yang Xu, Quanbin Zhang, Dali Luo
Non-alcoholic fatty-liver disease (NAFLD), caused by elevated hepatic lipids, inflammation and oxidative stress, is the most common liver disease globally. Low molecular weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweeds, has shown strong anti-inflammatory and antioxidant activities, which has not been explored in diabetes-induced NAFLD. Therefore, the present study sought to determine whether LMWF protects obese diabetic db/db mice against NAFLD. Results showed LMWF administration decreased plasma level of alanine aminotransferase, aspartate aminotransferase, total cholesterol, and triglyceride, as well as alleviated hepatic accumulation of triglyceride and total cholesterol in db/db mice...
February 12, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29445083/fibroblast-growth-factor-21-prevents-diabetic-cardiomyopathy-via-ampk-mediated-antioxidation-and-lipid-lowering-effects-in-the-heart
#18
Hong Yang, Anyun Feng, Sundong Lin, Lechu Yu, Xiufei Lin, Xiaoqing Yan, Xuemian Lu, Chi Zhang
Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammation, and oxidative stress, which was aggravated in FGF21-KO mice...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29441061/profiling-of-human-molecular-pathways-affected-by-retrotransposons-at-the-level-of-regulation-by-transcription-factor-proteins
#19
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29433631/ampk-signaling-to-acetyl-coa-carboxylase-is-required-for-fasting-and-cold-induced-appetite-but-not-thermogenesis
#20
Sandra Galic, Kim Loh, Lisa Murray-Segal, Gregory R Steinberg, Zane B Andrews, Bruce E Kemp
AMP-activated protein kinase (AMPK) is a known regulator of whole-body energy homeostasis, but the downstream AMPK substrates mediating these effects are not entirely clear. AMPK inhibits fatty acid synthesis and promotes fatty acid oxidation by phosphorylation of acetyl-CoA carboxylase (ACC) 1 at Ser 79 and ACC2 at Ser 212 . Using mice with Ser 79 Ala/Ser 212 Ala knock-in mutations (ACC DKI) we find that inhibition of ACC phosphorylation leads to reduced appetite in response to fasting or cold exposure. At sub-thermoneutral temperatures, ACC DKI mice maintain normal energy expenditure and thermogenesis, but fail to increase appetite and lose weight...
February 13, 2018: ELife
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