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https://www.readbyqxmd.com/read/27922115/perilipin-5-fine-tunes-lipid-oxidation-to-metabolic-demand-and-protects-against-lipotoxicity-in-skeletal-muscle
#1
Claire Laurens, Virginie Bourlier, Aline Mairal, Katie Louche, Pierre-Marie Badin, Etienne Mouisel, Alexandra Montagner, André Marette, Angelo Tremblay, John S Weisnagel, Hervé Guillou, Dominique Langin, Denis R Joanisse, Cedric Moro
Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913612/mechanisms-in-endocrinology-skeletal-muscle-lipotoxicity-in-insulin-resistance-and-type-2-diabetes-a-causal-mechanism-or-an-innocent-bystander
#2
REVIEW
Charlotte Brøns, Louise Groth Grunnet
Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27906700/update-on-lipid-species-and-paediatric-nonalcoholic-fatty-liver-disease
#3
Jake P Mann, Ariel E Feldstein, Valerio Nobili
PURPOSE OF REVIEW: To describe the recent advances in our understanding of fatty acids and lipids in paediatric nonalcoholic fatty liver disease (NAFLD) and their future implications. RECENT FINDINGS: Data have been accumulated to suggest that ceramides are the main drivers of hepatic insulin resistance in NAFLD, and inhibition of ceramide synthesis improves histology in mice.Saturated fatty acids formed by de novo lipogenesis generate increased lipotoxicity compared with dietary-derived saturated fatty acids...
November 30, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/27892502/mitochondrial-fat-oxidation-is-essential-for-lipid-induced-inflammation-in-skeletal-muscle-in-mice
#4
Jaycob D Warfel, Estrellita M Bermudez, Tamra M Mendoza, Sujoy Ghosh, Jingying Zhang, Carrie M Elks, Randall Mynatt, Bolormaa Vandanmagsar
Inflammation, lipotoxicity and mitochondrial dysfunction have been implicated in the pathogenesis of obesity-induced insulin resistance and type 2 diabetes. However, how these factors are intertwined in the development of obesity/insulin resistance remains unclear. Here, we examine the role of mitochondrial fat oxidation on lipid-induced inflammation in skeletal muscle. We used skeletal muscle-specific Cpt1b knockout mouse model where the inhibition of mitochondrial fatty acid oxidation results in accumulation of lipid metabolites in muscle and elevated circulating free fatty acids...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27890642/protective-effect-of-quercetin-on-high-fat-diet-induced-non-alcoholic-fatty-liver-disease-in-mice-is-mediated-by-modulating-intestinal-microbiota-imbalance-and-related-gut-liver-axis-activation
#5
David Porras, Esther Nistal, Susana Martínez-Flórez, Sandra Pisonero-Vaquero, José Luis Olcoz, Ramiro Jover, Javier González-Gallego, María Victoria García-Mediavilla, Sonia Sánchez-Campos
Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27884963/ectopic-fat-deposition-contributes-to-age-associated-pathology-in-caenorhabditis-elegans
#6
Konstantinos Palikaras, Meropi Mari, Barbara Petanidou, Angela Pasparaki, George Filippidis, Nektarios Tavernarakis
Age-dependent collapse of lipid homeostasis results in spillover of lipids and excessive fat deposition in non-adipose tissues. Ectopic fat contributes to lipotoxicity and has been implicated in the development of a metabolic syndrome that increases risk of age-associated diseases. However, the molecular mechanisms coupling ectopic fat accumulation with ageing remain obscure. Here, we use nonlinear imaging modalities to visualize and quantify age-dependent ectopic lipid accumulation in Caenorhabditis elegans...
November 24, 2016: Journal of Lipid Research
https://www.readbyqxmd.com/read/27881673/sortilin-1-modulates-hepatic-cholesterol-lipotoxicity-in-mice-via-functional-interaction-with-liver-carboxylesterase-1
#7
Jibiao Li, Yifeng Wang, David Matye, Hemantkumar Chavan, Partha Krishnamurthy, Feng Li, Tiangang Li
Liver plays a key role in cholesterol metabolism. Impaired hepatic cholesterol homeostasis causes intracellular free cholesterol accumulation and hepatocyte injury. Sortilin 1 (Sort1) is an intracellular lysosomal trafficking receptor that was recently identified by GWAS as a novel regulator of cholesterol metabolism in humans. Here we report that Sort1 deficiency protected against cholesterol accumulation-induced liver injury and inflammation in mice. Using LC-MS/MS based proteomics approach, we identified liver carboxyesterase 1 (CES1) as a novel Sort1 interacting protein...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27879673/4-hydroxyisoleucine-from-fenugreek-trigonella-foenum-graecum-effects-on-insulin-resistance-associated-with-obesity
#8
REVIEW
Anaguiven Avalos-Soriano, Ricardo De la Cruz-Cordero, Jorge L Rosado, Teresa Garcia-Gasca
Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity...
November 22, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27873157/eicosapentaenoic-acid-triggers-ca-2-release-and-ca-2-influx-in-mouse-cerebral-cortex-endothelial-bend-3-cells
#9
King-Chuen Wu, Kar-Lok Wong, Mei-Ling Wang, Lian-Ru Shiao, Iat-Lon Leong, Chi-Li Gong, Ka-Shun Cheng, Paul Chan, Yuk-Man Leung
Eicosapentaenoic acid (EPA), an omega-3 fatty acid abundant in fish oil, protects endothelial cells (EC) from lipotoxicity and triggers EC NO release. The latter is related to an elevation of cytosolic Ca(2+). Although EPA has been shown to cause human EC cytosolic Ca(2+) elevation, the mechanism is unclear. Microfluorimetric imaging was used here to measure free cytosolic Ca(2+) concentration. EPA was shown to cause intracellular Ca(2+) release in mouse cerebral cortex endothelial bEND.3 cells; interestingly, the EPA-sensitive intracellular Ca(2+) pool(s) appeared to encompass and was larger than the Ca(2+) pool mobilized by sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase inhibition by cyclopiazonic acid...
November 21, 2016: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27873093/fatty-acids-in-a-high-fat-diet-potentially-induce-gastric-parietal-cell-damage-and-metaplasia-in-mice
#10
Yuki Hirata, Takuhito Sezaki, Miwa Tamura-Nakano, Chinatsu Oyama, Teruki Hagiwara, Takamasa Ishikawa, Shinji Fukuda, Kazuhiko Yamada, Kazuhide Higuchi, Taeko Dohi, Yuki I Kawamura
BACKGROUND: Obesity is associated with risk of adenocarcinoma in the proximal stomach. We aimed to identify the links between dietary fat and gastric premalignant lesions. METHODS: C57BL/6 mice were fed high fat diet (HFD), and gastric mucosa was histologically analysed. Morphological changes were also analysed using an electron microscope. Transcriptome analysis of purified parietal cells was performed, and non-parietal gastric corpus epithelial cells were subjected to single-cell gene-expression profiling...
November 21, 2016: Journal of Gastroenterology
https://www.readbyqxmd.com/read/27871808/new-mechanism-of-lipotoxicity-in-diabetic-cardiomyopathy-deficiency-of-endogenous-h2s-production-and-er-stress
#11
Runmin Guo, Zijun Wu, Jiamei Jiang, Chang Liu, Bin Wu, Xingyue Li, Teng Li, Hailiang Mo, Songjian He, Shanghai Li, Hai Yan, Ruina Huang, Qiong You, Keng Wu
OBJECTIVE: To investigate the roles and mechanisms of endogenous hydrogen sulfide (H2S) and endoplasmic reticulum (ER) stress in the development of diabetic cardiomyopathy (DCM). METHODS: Blood of DCM patients included in the study were collected. The model of DCM rats was established using streptozotocin (STZ) injection. Cardiac lipotoxicity in vitro models were established using 500μM palmitic acid (PA) treatment for 24h in AC16 cardiomyocytes. Endogenous H2S production in plasma, culture supernatant and heart was measured by sulphur ion-selective electrode assay...
November 18, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27870654/dietary-fatty-acid-metabolism-in-prediabetes
#12
Christophe Noll, André C Carpentier
PURPOSE OF REVIEW: Experimental evidences are strong for a role of long-chain saturated fatty acids in the development of insulin resistance and type 2 diabetes. Ectopic accretion of triglycerides in lean organs is a characteristic of prediabetes and type 2 diabetes and has been linked to end-organ complications. The contribution of disordered dietary fatty acid (DFA) metabolism to lean organ overexposure and lipotoxicity is still unclear, however. DFA metabolism is very complex and very difficult to study in vivo in humans...
November 18, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27866836/physiological-suppression-of-lipotoxic-liver-damage%C3%A2-by-complementary-actions-of-hdac3-and%C3%A2-scap-srebp
#13
Romeo Papazyan, Zheng Sun, Yong Hoon Kim, Paul M Titchenell, David A Hill, Wenyun Lu, Manashree Damle, Min Wan, Yuxiang Zhang, Erika R Briggs, Joshua D Rabinowitz, Mitchell A Lazar
Liver fat accumulation precedes non-alcoholic steatohepatitis, an increasing cause of end-stage liver disease. Histone deacetylase 3 (HDAC3) is required for hepatic triglyceride homeostasis, and sterol regulatory element binding protein (SREBP) regulates the lipogenic response to feeding, but the crosstalk between these pathways is unknown. Here we show that inactivation of SREBP by hepatic deletion of SREBP cleavage activating protein (SCAP) abrogates the increase in lipogenesis caused by loss of HDAC3, but fatty acid oxidation remains defective...
November 10, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27864687/omega-3-fatty-acid-epa-improves-regenerative-capacity-of-mouse-skeletal-muscle-cells-exposed-to-saturated-fat-and-inflammation
#14
Amarjit Saini, Adam P Sharples, Nasser Al-Shanti, Claire E Stewart
Sarcopenic obesity is characterised by high fat mass, low muscle mass and an elevated inflammatory environmental milieu. We therefore investigated the effects of elevated inflammatory cytokine TNF-α (aging/obesity) and saturated fatty acid, palmitate (obesity) on skeletal muscle cells in the presence/absence of EPA, a-3 polyunsaturated fatty acid with proposed anti-inflammatory, anti-obesity activities. In the present study we show that palmitate was lipotoxic, inducing high levels of cell death and blocking myotube formation...
November 18, 2016: Biogerontology
https://www.readbyqxmd.com/read/27863448/lipid-zonation-and-phospholipid-remodeling-in-non-alcoholic-fatty-liver-disease
#15
Zoe Hall, Nicholas J Bond, Tom Ashmore, Francis Sanders, Zsuzsanna Ament, Xinzhu Wang, Andrew J Murray, Elena Bellafante, Sam Virtue, Antonio Vidal-Puig, Michael Allison, Susan E Davies, Albert Koulman, Michele Vacca, Julian L Griffin
: Non-alcoholic fatty liver disease (NAFLD) can progress from 'simple steatosis' (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis and cancer. Currently the driver for this progression is not fully understood; in particular it is not known how NAFLD and its early progression affects the distribution of lipids in the liver, producing lipotoxicity and inflammation. Here we use dietary and genetic mouse models of NAFL and NASH, and translate results to humans, by correlating the spatial distribution of lipids in liver tissue with disease progression, using advanced mass spectrometry imaging technology...
November 18, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27851965/adipose-snail1-regulates-lipolysis-and-lipid-partitioning-by-suppressing-adipose-triacylglycerol-lipase-expression
#16
Chengxin Sun, Lin Jiang, Yan Liu, Hong Shen, Stephen J Weiss, Yifa Zhou, Liangyou Rui
Lipolysis provides metabolic fuel; however, aberrant adipose lipolysis results in ectopic lipid accumulation and lipotoxicity. While adipose triacylglycerol lipase (ATGL) catalyzes the first step of lipolysis, its regulation is not fully understood. Here, we demonstrate that adipocyte Snail1 suppresses both ATGL expression and lipolysis. Adipose Snail1 levels are higher in fed mice than in fasted mice and higher in obese mice as opposed to lean mice. Insulin increases Snail1 levels in both murine and human adipocytes, wherein Snail1 binds to the ATGL promoter to repress its expression...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27847215/grape-seed-and-skin-extract-reduces-pancreas-lipotoxicity-oxidative-stress-and-inflammation-in-high-fat-diet-fed-rats
#17
Faten Aloui, Kamel Charradi, Aziz Hichami, Selvakumar Subramaniam, Naim Akhtar Khan, Ferid Limam, Ezzedine Aouani
Obesity is related to an elevated risk of diabetes and the mechanisms whereby fat adversely affects the pancreas are poorly understood. We studied the effect of a high fat diet (HFD) on pancreas steatosis, oxidative stress and inflammation as well as the putative protection afforded by grape seed and skin extract (GSSE). HFD induced body weight gain, without affecting insulinemia, nor glycemia and dropped adiponectemia. HFD also provoked the ectopic deposition of cholesterol and triglyceride, and an oxidative stress characterized by increased lipoperoxidation and carbonylation, inhibition of antioxidant enzyme activities such as CAT, GPx and SOD, depletion of zinc and a concomitant increase in calcium and H2O2...
November 12, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27846372/loss-of-ulk1-increases-rps6kb1-ncor1-repression-of-nr1h-lxr-mediated-scd1-transcription-and-augments-lipotoxicity-in-hepatic-cells
#18
Rohit Anthony Sinha, Brijesh K Singh, Jin Zhou, Sherwin Xie, Benjamin L Farah, Ronny Lesmana, Kenji Ohba, Madhulika Tripathi, Sujoy Ghosh, Anthony N Hollenberg, Paul M Yen
Lipotoxicity caused by saturated fatty acids (SFAs) induces tissue damage and inflammation in metabolic disorders. SCD1 (stearoyl-Coenzyme A desaturase 1) converts SFAs to mono-unsaturated fatty acids (MUFAs) that are incorporated into triglycerides and stored in lipid droplets. SCD1 thus helps protect hepatocytes from lipotoxicity and its reduced expression is associated with increased lipotoxic injury in cultured hepatic cells and mouse models. To further understand the role of SCD1 in lipotoxicity, we examined the regulation of Scd1 in hepatic cells treated with palmitate, and found that NR1H/LXR (nuclear receptor subfamily 1 group H) ligand, GW3965, induced Scd1 expression and lipid droplet formation to improve cell survival...
November 15, 2016: Autophagy
https://www.readbyqxmd.com/read/27845866/a-canola-oil-supplemented-diet-prevents-type-i-diabetes-caused-lipotoxicity-and-renal-dysfunction-in-a-rat-model
#19
Edgar Cano-Europa, Rocio Ortiz-Butron, Estela Melendez Camargo, María Miriam Esteves-Carmona, Rosa Maria Oliart-Ros, Vanessa Blas-Valdivia, Margarita Franco-Colin
We investigated the effect of a canola oil-supplemented diet on the metabolic state and diabetic renal function of a type I diabetes experimental model. Male Sprague-Dawley rats were randomly divided into four groups: (1) normoglycemic+chow diet, (2) normoglycemic+a canola oil-supplemented chow diet, (3) diabetic+chow diet, and (4) diabetic+a canola oil-supplemented chow diet. For 15 weeks, animals were fed a diet of Purina rat chow alone or supplemented with 30% canola oil. Energetic intake, water intake, body weight, and adipose tissue fat pad were measured; renal function, electrolyte balance, glomerular filtration rate, and the plasmatic concentration of free fatty acids, cholesterol, triglycerides, and glucose were evaluated...
November 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/27843479/protective-effect-of-psoralea-corylifolia-l-seed-extract-against-palmitate-induced-neuronal-apoptosis-in-pc12-cells
#20
Yunkyoung Lee, Hee-Sook Jun, Yoon Sin Oh
The extract of Psoralea corylifolia seeds (PCE) has been widely used as a herbal medicine because of its beneficial effect on human health. In this study, we investigated the protective effects and molecular mechanisms of PCE on palmitate- (PA-) induced toxicity in PC12 cells, a neuron-like cell line. PCE significantly increased cell viability in PA-treated PC12 cells and showed antiapoptotic effects, as evidenced by decreased expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and bax protein as well as increased expression of bcl-2 protein...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
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