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ampk regulation of fatty acids

Liliana F Iannucci, Jingfeng Sun, Brijesh K Singh, Jin Zhou, Vincent A Kaddai, Antonia Lanni, Paul M Yen, Rohit A Sinha
Short-chain fatty acids (SCFAs) are gut microbial fermentation products derived from dietary fiber sources. Although depletion of gut microflora has been linked to the development of liver disease, the direct effects of SCFAs on intracellular hepatic processes are not well understood. In this study, we demonstrated that the SCFAs, propionate and butyrate, regulated autophagic flux in hepatic cells in a cell-autonomous manner. Induction of autophagy by SCFAs required PPARγ stimulation of Uncoupling Protein 2 (UCP2) expression that was associated with reduced intracellular ATP levels and activation of PRKAA1/AMPK (protein kinase, AMP-activated, alpha 1 catalytic subunit)...
October 20, 2016: Biochemical and Biophysical Research Communications
John J Guardiola, Juliane I Beier, K Cameron Falkner, Benjamin Wheeler, Craig James McClain, Matt Cave
BACKGROUND: Occupational vinyl chloride (VC) exposures have been associated with toxicant-associated steatohepatitis and liver cancer. Metabolomics has been used to clarify mode of action in drug-induced liver injury but has not been performed following VC exposures. METHODS: Plasma samples from 17 highly exposed VC workers without liver cancer and 27 unexposed healthy volunteers were obtained for metabolite extraction and GC/MS and LC/MS(2) analysis. Following ion identification/quantification, Ingenuity pathway analysis was performed...
October 17, 2016: Toxicology and Applied Pharmacology
Z Q Lu, Y Ren, X H Zhou, X F Yu, J Huang, D Y Yu, X X Wang, Y Z Wang
As meat quality is basically dependent on muscle fibre characteristics, it is important to know how muscle fibres are regulated and transformed. This study aimed to investigate the effect of maternal dietary supplementation on muscle fibre types using 3% saturated fatty acid (palmitic acid, PA) or 3% unsaturated fatty acid (linoleic acid, LA) from 80 days of gestation to the weaning of offspring (25 days post-natal). The results indicated that higher mRNA levels of MyHCI type genes were found in the soleus muscles of piglets that suckled from LA-supplemented sows than from PA-supplemented sows...
October 20, 2016: Journal of Animal Physiology and Animal Nutrition
Xu Zhang, Qianni Cheng, Yixiang Wang, Po Sing Leung, Kinglun Kingston Mak
Bone plays a role in energy metabolism, but the interplay between bone and other organs in this process is not completely understood. Here, we show that upregulated Hh signaling in bones results in increased whole-body energy expenditure, white adipose tissue (WAT) browning, hypoglycemia and skeletal muscle atrophy. We found that Hh signaling induces PTHrP secretion from bones and causes WAT browning. Injection of PTHrP-neutralizing antibody attenuates WAT browning and improves the circulating blood glucose level while high-fat diet treatment only rescues hypoglycemia...
October 14, 2016: Cell Death and Differentiation
Luciano Galdieri, Himavanth Gatla, Ivana Vancurova, Ales Vancura
AMP-activated protein kinase (AMPK) is an energy sensor and master regulator of metabolism. AMPK functions as a fuel gauge monitoring systemic and cellular energy status. Activation of AMPK occurs when the intracellular AMP/ATP ratio increases and leads to a metabolic switch from anabolism to catabolism. AMPK phosphorylates and inhibits acetyl-CoA carboxylase (ACC), which catalyzes carboxylation of acetyl-CoA to malonyl-CoA, the first and rate-limiting reaction in de-novo synthesis of fatty acids. AMPK thus regulates homeostasis of acetyl-CoA, a key metabolite at the crossroads of metabolism, signaling, chromatin structure, and transcription...
October 12, 2016: Journal of Biological Chemistry
Ismael González-García, Johan Fernø, Carlos Diéguez, Rubén Nogueiras, Miguel López
Hypothalamic lipid metabolism plays a major role in the physiological regulation of energy balance. Modulation of several enzymatic activities that control lipid biosynthesis, such as fatty acid synthase (FAS) and AMP-activated protein kinase (AMPK), impacts both feeding and energy expenditure. However, lipids can also cause pathological alterations in the hypothalamus. Lipotoxicity is promoted by excess lipids in tissues non suitable for their storage. A large amount of evidence has demonstrated that lipotoxicity is a pathophysiological mechanism leading to metabolic diseases, such as insulin resistance, cardiomyopathy, atherosclerosis and steatohepatitis...
October 11, 2016: Neuroendocrinology
Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E Scherer, Tiemin Liu, Kevin W Williams
OBJECTIVE: Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation - including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined...
October 2016: Molecular Metabolism
Bruno G Teodoro, Igor H Sampaio, Lucas H M Bomfim, André L Queiroz, Leonardo R Silveira, Anderson O Souza, Anna M A P Fernandes, Marcos N Eberlin, Tai-Yu Huang, Donghai Zheng, P Darrell Neufer, Ronald N Cortright, Luciane C Alberici
Long-chain Acyl-CoA Synthetases (ACSL 1 to 6) are key enzymes regulating partitioning of acyl-CoA species toward different metabolic fates such as lipid synthesis or β-oxidation. Despite the understanding that ecotopic lipid accumulation in skeletal muscle is associated with metabolic diseases like obesity and Type II Diabetes, the role of specific ACSL isoforms in lipid synthesis remains unclear. Herein we describe for the first time the presence of ACSL6 mRNA in human skeletal muscle and the role that ACSL6 plays in lipid synthesis in both rodent and human skeletal muscle...
September 20, 2016: Journal of Physiology
Sukriti Krishan, Des R Richardson, Sumit Sahni
Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor that monitors ATP levels. There is also evidence that AMPK has onco-suppressive properties. Iron plays a crucial role in cellular energy transducing pathways and tumor cell proliferation. Therefore, metals (e.g., iron) could play an important role in the regulation of AMPK-dependent pathways. Hence, this investigation examined the effect of the iron and copper chelator and potent anti-cancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on the AMPK-mediated pathway...
September 15, 2016: Biochimica et Biophysica Acta
L M Laiglesia, S Lorente-Cebrián, P L Prieto-Hontoria, M Fernández-Galilea, S M R Ribeiro, N Sáinz, J A Martínez, M J Moreno-Aliaga
Eicosapentaenoic acid (EPA), a n-3 long-chain polyunsaturated fatty acid, has been reported to have beneficial effects in obesity-associated metabolic disorders. The objective of the present study was to determine the effects of EPA on the regulation of genes involved in lipid metabolism, and the ability of EPA to induce mitochondrial biogenesis and beiging in subcutaneous adipocytes from overweight subjects. Fully differentiated human subcutaneous adipocytes from overweight females (BMI: 28.1-29.8kg/m(2)) were treated with EPA (100-200 μM) for 24 h...
August 26, 2016: Journal of Nutritional Biochemistry
Sabrina Chriett, Ouafa Zerzaihi, Hubert Vidal, Luciano Pirola
Dietary administration of the histone deacetylase (HDAC) inhibitor butyric acid - a short chain fatty acid present in milk products and also bacterially produced in the intestine - has been shown to increase energy expenditure and favour insulin sensitivity in mice through induction of PGC1α (peroxisome proliferator-activated receptor gamma co-activator 1α) and AMPK (AMP-activated protein kinase) in skeletal muscle, and a consequential increase of mitochondrial fatty acid oxidation. Here, we investigate whether such physiological improvements are associated to epigenetic effects dependent on increased histone acetylation and whether butyrate exerts a direct action on skeletal muscle insulin signalling...
September 9, 2016: Molecular and Cellular Endocrinology
Ji-Hye Lee, Jung-Jin Lee, Won-Kyung Cho, Nam-Hui Yim, Hyun-Kyu Kim, Bora Yun, Jin Yeul Ma
BACKGROUND: KBH-1 is an herbal mixture of Saururus chinensis, Curcuma longa and Polygala tenuifolia. Each herb has been reported to have various pharmaceutical activities; however, the synergistic effect of this herbal composition on obesity has not yet been determined. We investigated the alleviation effect of KBH-1 and its possible molecular mechanism in obesity-induced hepatic steatosis and leptin resistance in the hypothalamus. METHODS: We used HepG2 cells, primary neuronal cells and a high-fat diet (HFD)-induced obesity rat model to determine the effect of KBH-1 in vitro and in vivo on hepatic steatosis and leptin resistance accompanied by obesity...
2016: BMC Complementary and Alternative Medicine
Karen P Briski, Fahaad S H Alenazi, Manita Shakya, Paul W Sylvester
Estradiol (E) mitigates acute and postacute adverse effects of 12 hr-food deprivation (FD) on energy balance. Hindbrain 5'-monophosphate-activated protein kinase (AMPK) regulates hyperphagic and hypothalamic metabolic neuropeptide and norepinephrine responses to FD in an E-dependent manner. Energy-state information from AMPK-expressing hindbrain A2 noradrenergic neurons shapes neural responses to metabolic imbalance. Here we investigate the hypothesis that FD causes divergent changes in A2 AMPK activity in E- vs...
September 12, 2016: Journal of Neuroscience Research
Dmitry Namgaladze, Bernhard Brüne
Recent research considerably changed our knowledge how cellular metabolism affects the immune system. We appreciate that metabolism not only provides energy to immune cells, but also actively influences diverse immune cell phenotypes. Fatty acid metabolism, particularly mitochondrial fatty acid oxidation (FAO) emerges as an important regulator of innate and adaptive immunity. Catabolism of fatty acids also modulates the progression of disease, such as the development of obesity-driven insulin resistance and type II diabetes...
September 7, 2016: Biochimica et Biophysica Acta
Marcel Boß, Yvette Newbatt, Sahil Gupta, Ian Collins, Bernhard Brüne, Dmitry Namgaladze
Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty acids (SFA), and endoplasmic reticulum (ER) stress responses essentially contribute to pro-inflammatory signalling. AMP-activated protein kinase (AMPK) is a central metabolic regulator with established anti-inflammatory actions. Whether pharmacological AMPK activation suppresses SFA-induced inflammation in a human system is unclear...
2016: Scientific Reports
Jamie I Baum, Tyrone A Washington, Stephanie A Shouse, Walter Bottje, Sami Dridi, Gina Davis, Dameon Smith
Obesity is a major public health concern and it is essential to identify effective treatments and preventative strategies to stop continued increases in obesity rates. The potential functional roles of the branched chain amino acid leucine make this amino acid an attractive candidate for the treatment and/or prevention of obesity. The objective of this study was to determine if long-term leucine supplementation could prevent the development of obesity and reduce the risk factors for chronic disease in rats fed a high-fat (60 % fat) diet...
August 20, 2016: Journal of Physiology and Biochemistry
Hong Jian, Jia Yimin, Pan Shifeng, Jia Longfi, Li Huifang, Han Zhenqiang, Cai Demin, Zhao Ruqian
Dietary supplementation of butyrate can prevent diet-induced obesity through increasing mitochondrial function in mice, yet the up-stream signaling pathway remains elusive. In this study, weaned mice were divided into two groups, fed control (CON) and high-fat diet (HF, 45% energy from fat), respectively, for 8 weeks. HF-induced obese mice, maintained on HF diet, were then divided into two groups; HFB group was gavaged with 80 mg sodium butyrate (SB) per mice every other day for 10 days, while the HF group received vehicle...
August 12, 2016: Oncotarget
Guido A Gualdoni, Katharina A Mayer, Lisa Göschl, Nicole Boucheron, Wilfried Ellmeier, Gerhard J Zlabinger
T cells must tightly regulate their metabolic processes to cope with varying bioenergetic demands depending on their state of differentiation. The metabolic sensor AMPK is activated in states of low energy supply and modulates cellular metabolism toward a catabolic state. Although this enzyme is known to be particularly active in regulatory T (Treg) cells, its impact on T helper (Th) cell differentiation is poorly understood. We investigated the impact of several AMPK activators on Treg differentiation and found that the direct activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), but not the indirect activators metformin and 2-deoxyglucose, strongly enhanced Treg cell induction by specifically enhancing Treg cell expansion...
August 4, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Shaojie Wang, Xiaojie Li, Hongli Guo, Zihang Yuan, Tao Wang, Luyong Zhang, Zhenzhou Jiang
AIM: To investigate the effects of emodin on the treatment of nonalcoholic fatty liver and the underlying mechanisms. METHODS: In vitro, hepatocytes were treated with 1 mM free fatty acid (FFA) together with various concentrations of emodin. In vivo, Sprague-Dawley rats were divided into the control, high-fat diet (HFD) group, and three HFD groups treated with 40, 80 and 160 mg/kg emodin, respectively. After being fed a HFD for four weeks, rats were orally dosed with emodin once daily for 8 weeks...
August 4, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Tushar P Patel, Komal Rawal, Sanket Soni, Sarita Gupta
Swertiamarin, a bitter secoiridoid glycoside, is an antidiabetic drug with lipid lowering activity meliorates insulin resistance in Type 2 Diabetes condition. Therefore, the study was designed to explore the antioxidant and hypolipidemic activity of swertiamarin in ameliorating NAFLD caused due to hepatic lipid accumulation, inflammation and insulin resistance. Steatosis was induced in HepG2 cells by supplementing 1mM oleic acid (OA) for 24h which was marked by significant accumulation of lipid droplets. This was determined by Oil Red O (ORO) staining and triglyceride accumulation...
August 1, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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