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| 1 | High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells显示文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown. A high ratio may promote lipogenic pathways and contribute to reactive oxygen species(ROS)-mediated damage, perhaps leading to mitochondrial dysfunction.Therefore, these parameters were investigated to understand their contribution to NAFLD development.AIM To examine the effect of increasing ratios of omega-6:3 fatty acids on mitochondrial function and lipid metabolism mediators.METHODS Hep G2-derived VL-17 A cells were treated with normal(1:1, 4:1) and high(15:1,25:1) ratios of omega-6: omega-3 fatty acids [arachidonic acid(AA):docosahexaenoic acid(DHA)] at various time points. Mitochondrial activity and function were examined via MTT assay and Seahorse XF24 analyzer, respectively.Triglyceride accumulation was determined by using Enzy Chrom? and levels of ROS were measured by fluorescence intensity. Protein expression of the mediators of lipogenic, lipolytic and endocannabinoid pathways was assessed by Western blotting.RESULTS High AA:DHA ratio decreased mitochondrial activity(P < 0.01;up to 80%) and promoted intracellular triglyceride accumulation(P < 0.05;40%-70%).Mechanistically, it altered the mediators of lipid metabolism;increased the expression of stearoyl-Co A desaturase(P < 0.05;22%-35%), decreased the expression of peroxisome proliferator-activated receptor-alpha(P < 0.05;30%-40%) and increased the expression of cannabinoid receptor 1(P < 0.05;31%).Furthermore, the high ratio increased ROS production(P < 0.01;74%-115%) and reduced mitochondrial respiratory functions such as basal and maximal respiration, ATP production, spare respiratory capacity and proton leak(P < 0.01;35%-68%).CONCLUSION High AA:DHA ratio induced triglyceride accumulation, increased oxidative stress and disrupted mitochondrial functions. Stimulation of lipogenic and steroidal transcription factors may partly mediate these effects and contribute to NAFLD development. | Reem Ghazali Kosha J Mehta SW Annie Bligh Ihab Tewfik Dahn Clemens Vinood B Patel | 2020 | World Journal of Hepatology2020，12，3： | 2 |
| 2 | An approach for functional synthesis of mechanical design concept: theory, applications, and emerging research issues 显示文摘 | Chakrabarti A Bligh T P | 1996 | Artificial Intelligence for Engineering Design Analysis and Manufacturing1996，10，4： | 1 |
| 3 | A rapid method oftotle lipid extraction and puffcation显示文摘 | BLIGH EG DYER WJ | 1959 | Can J Phsiol Phram1959，37，8： | 1 |
| 4 | Recent perspectives on clinical teaching显示文摘 | I Parsell G Bligh J | 2011 | Medi- cal Education2011，35，4： | 1 |
| 5 | Simultaneous determination of six alkaloids and one monoterpene in rat plasma by liquid chromatography–tandem mass spectrometry and pharmacokinetic study after oral administration of a Chinese medicine Wuji Pill显示文摘 | Jin Yuan Ying Wang Rui An Shuang Wang Shui-Jun Li Jing-Ying Jia S.W. Annie Bligh Xin-Hong Wang Yue-ming Ma | 2012 | Journal of Chromatography B2012，，： | 1 |
| 6 | A microsatelllte sequence closely linked to the waxy gene of Oryza sativa显示文摘 | Bligh H F J Till R I Jones C A | 1995 | Euphytica1995，86，： | 1 |
| 7 | SenseCam image localisation using hierarchical SURF trees显示文摘 | Oconaire C Blighe M Oconno N | 2009 | Springer-Verlag Berlin Heidelberg2009，9，1： | 1 |
| 8 | Simulataneous determination of six isoflavonoids in commercial Radix Astragali by HPLC-UV显示文摘 | Wu T Bligh SWA Gu LH | 2005 | Fitoterapia2005，，76： | 1 |
| 9 | A rapid method for total lipid extraction and purification显示文摘 | Bligh EG Dyer WJ | 1959 | Can J Biochem Physiol1959，37，8： | 1 |
| 10 | A rapid method of total lipid extraction and purification显示文摘 | Bligh E G Dyer W J | 1959 | Canadian Journal of Biochemistry and Physiology1959，37，8： | 1 |
| 11 | The importance of self-and shared leadership in team based knowledge work:A mesolevel model of leadership dynamics显示文摘 | BLIGH M C PEARCE C L KHOLES G C | 2006 | Journal of Managerial Psychology2006，21，4： | 1 |
| 12 | A rapid method of total lipid extraction and purification 显示文摘 | BLIGH E G DYER W J | 1959 | Can J Biochem Physiol1959，37，8： | 1 |
| 13 | Serological speciation of human schistosome infections by ELISA with a panel of three antigens显示文摘 | Turner P Lalloo K Bligh J | 2004 | Pathol2004，57，： | 1 |
| 14 | A rapid method of lipid extraction and pur-ification显示文摘 | Bligh E G Dyer W M | 1959 | Canada Journal of Biochemistry and Physiology1959，37，： | 1 |
| 15 | Mind-mapped care plan:a remarkable ahernative to traditional nursing care plans显示文摘 | Mueller A Johnston M Bligh D | 2001 | Nurse Educ2001，26，2： | 1 |
| 16 | Information technology in medical education: current and future applications 显示文摘 | Mooney GA Bligh JG | 2006 | Postgrad Med J2006，73，865： | 1 |
| 17 | A rapid method for total lipid extraction and purification 显示文摘 | Bligh E G Dyer W J | 1959 | Can J Biochem Physiol1959，37，： | 1 |
| 18 | A Rapid Method of Total Lipid Extraction and Purification显示文摘 | BLIGH EG DYER WJ | 1959 | Canadian Journal of Bio- chemistry and Physiology1959，37，8： | 1 |
| 19 | Teaching anatomy without cadavers显示文摘 | Mclachian JC Bligh J Bradley P | | 0，，4： | 1 |
| 20 | Microsatellites and a single-nucleotide polymorphism differentiate apparentamylose classes in an extended pedigree of US rice germ plasm显示文摘 | N. M. Ayres A. M. McClung P. D. Larkin H. F. J. Bligh C. A. Jones W. D. Park | 1997 | TAG Theoretical and Applied Genetics (-)1997，，6： | 1 |
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