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Synthetic and Systems Biotechnology 2024年第1期9卷 144-151页

作者： Lixia Fang Ziyi Han Xueru Feng Xueyan Hao Mengxiao Liu Hao Song Yingxiu Cao Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education) School of Chemical Engineering and TechnologyTianjin UniversityTianjin300072China Frontiers Research Institute for Synthetic Biology Tianjin UniversityChina

Transcription factor engineering has unique advantages in improving the performance of microbial cell factories due to the global regulation of gene *** analyses and reverse engineering enable learning and subsequent incorporation of novel design strategies for further ***,we identify the role of the global regulator IhfA for overproduction of free fatty acids(FFAs)using CRISPRi-facilitated reverse engineering and cellular physiological *** the differentially expressed genes in the ihfAL􀀀strain,a total of 14 beneficial targets that enhance FFAs production by above 20% are identified,which involve membrane function,oxidative stress,and *** membrane-related genes,the engineered strains obtain lower cell surface hydrophobicity and increased average length of membrane lipid *** oxidative stress-related genes,the engineered strains present decreased reactive oxygen species(ROS)*** gene modulations enhance cellular robustness and save cellular resources,contributing to FFAs *** study provides novel targets and strategies for engineering microbial cell factories with improved FFAs bioproduction.

关键词： free fatty acids CRISPRi ihfA Cell membrane ROS

free fatty acids, glucose, and insulin in type 2 diabetes mellitus

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World Journal of Diabetes 2022年第3期13卷 275-277页

作者： Rob NM Weijers Teaching Hospital OLVGAmsterdam 95500Netherlands

Xu et al used the HOMA2 model to estimate theβ-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin *** method is based on the assumption that the glucose-insulin axis is central for the metabolic activities,which led to type 2 ***,significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids(FFAs)into the blood circulation,which leads to a marked reduction in membrane *** data favor a FFA-glucose-insulin *** authors are invited to extend their study with the introduction of the saturation index(number of carbon-carbon double bonds per 100 fatty-acyl chains),as observed in erythrocytes.

关键词： free fatty acids Membrane flexibility NKX2-1 gene RNA sequencing Type 2 diabetes TPD52L-3 gene Unsaturation index

Correlation between serum free fatty acids levels and Gensini score in elderly patients with coronary heart disease

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Journal of Geriatric Cardiology 2014年第1期11卷 57-62页

作者： Li-Yun HE Jun-Feng ZHAO Jiang-Li HAN Shan-Shan SHEN Xu-Jiao CHEN Department of Cardiology Peking University Third Hospital and Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry ofHealth Beijing 100191 China Department of Emergency the Third Affiliated Hospital of Zhejiang Chinese Medical University Hangzhou 310005 Zhejiang Province China Department of Geriatrics Zhejiang Hospital Hangzhou 310013 Zhejiang Province China

Objectives To investigate the relationship between serum fxee fatty acids （FFAs） levels and the severity of coronary artery lesions in elderly patients with coronary heart disease （CAD）. Methods A total of 172 elderly patients who underwent coronary angiography were divided into CAD group （n = 128） and non-CAD group （n = 44） according to the results of coronary angiography. Serum FFAs and lipid levels were measured and the Gensini score were calculated. Results No matter the differences between age, gender and the usage of stat- ins or not, there was no statistical significance in FFAs levels （P 〉 0.05）. In terms of the Gensini score, it was higher in patients aged 70-79 years than in patients 60-69 years old [15.00 （5.00, 34.00） vs. 10.00 （2.00, 24.00）, P 〈 0.05], higher in men than women [14.00 （4.00, 34.00） vs. 7.00 （2.50, 19.75）, P 〈 0.05], and higher in patients on statins [13.50 （4.25, 33.50）vs. 6.50 （2.00, 18.00）, P 〈 0.05]. The serum FFAs lev- els [449.50 （299.00, 624.75） mEq/L vs. 388.00 （258.50, 495.25） mEq/L, P 〈 0.05J and Gensini score [17.50 （8.00, 41.75） vs. 1.00 （0, 5.00）, P 〈 0.05] were higher in the CAD group than in the non-CAD group. In the CAD group, there was no statistical significance in FFAs levels among patients with different numbers of diseased coronary vessels （P 〉 0.05）. Furthermore, the FFAs levels were positively correlated with the Gensini score （r = 0.394, P = 0.005）. Regression analysis showed that the FFAs levels were related to the Gensini score independently after adjusting for the other risk factors. Conclusions The serum FFAs levels were associated with the Gensini score in elderly patients with CAD. It might indicate FFAs as a biomarker predicting the severity of coronary artery lesions.

关键词： Coronary heart disease free fatty acids Gensini score The elderly

Effects of different free fatty acids on insulin resistance in rats

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Hepatobiliary & Pancreatic Diseases International 2008年第1期7卷 91-96页

作者： Han, Ping Zhang, Yong-Yan Lu, Yan He, Bing Zhang, Wei Xia, Fei China Med Univ Affiliated Shengjing Hosp Dept Endocrinol Shenyang 110004 Peoples R China

BACKGROUND: Much evidence demonstrates that elevated free fatty acids (FFAs) are associated with insulin resistance. However, it is not clear whether different FFAs can cause different degrees of peripheral insulin resistance. This study aimed to investigate the effects of short-term elevation of FFAs on hepatic and peripheral insulin action, and determine whether FFAs with different degrees of saturation have differential effects on hepatic insulin resistance. METHODS: Intralipid+heparin (IH, polyunsaturated fatty acids), oleate (OLE), lard oil+heparin (LOH), and saline (SAL) were separately infused intravenously for 7 hours in normal Wistar rats. During the last 2 hours of the fat/saline infusion, a hyperinsulinemic-euglycemic clamping was performed with [6-H-3] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassays. Plasma FFAs were measured using a colorimetric method. RESULTS: Compared with infusion of SAL, plasma FFA levels were significantly elevated by infusions of IH, OLE, and LOH (Pfatty acids induced less hepatic insulin resistance than monounsaturated or saturated fatty acids. However, IH, OLE, and LOH infusions induced similar peripheral insulin resistance.

关键词： free fatty acids insulin resistance hepatic glucose production glucose utilization

Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids

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Hepatobiliary & Pancreatic Diseases International 2010年第1期9卷 49-53页

作者： He, Bing Zhao, Sheng Zhang, Wei Li, Yan Han, Ping China Med Univ Shengjing Affiliated Hosp Dept Endocrinol Shenyang 110004 Peoples R China China Med Univ Affiliated Hosp 4 Dept Internal Med Shenyang 110032 Peoples R China

BACKGROUND: It has been reported that high-dose salicylates improve free fatty acids (FFAs)-induced insulin resistance and beta-cell dysfunction in vitro, but the mechanism remains uncertain. In insulin-resistant rats, we found that the supplementation of sodium salicylate is associated with a reduction of plasma malondialdehyde (MDA), a marker of oxidative stress. Few studies have investigated the effects of salicylates on oxidative stress levels in insulin-resistant animal models. This study aimed to assess the effect of sodium salicylate on insulin sensitivity and to explore the potential mechanism by which it improves hepatic and peripheral insulin resistance. METHODS: Intralipid+heparin (IH), saline (SAL), or intralipid+heparin+sodium salicylate (IHS) were separately infused for 7 hours in normal Wistar rats. During the last 2 hours of the infusion, hyperinsulinemic-euglycemic clamping was 3 performed with [6-(3)H] glucose tracer. Plasma glucose was measured using the glucose oxygenase method. Plasma insulin and C-peptide were determined by radioimmunoassay. MDA levels and glutathione peroxidase (GSH-PX) activity in the liver and skeletal muscle were measured with colorimetric kits. RESULTS: Compared with infusion of SAL, IH infusion increased hepatic glucose production (HGP), and decreased glucose utilization (GU) (Pfree fatty acids increased the MDA levels and decreased the GSH-PX activity in the liver and muscle (Pfatty acids induces insulin resistance by enhancing oxidative stress levels in the liver and muscle. The administration of the anti-inflammatory drug sodium salicylate reduces the degree of oxidative stress, therefore improving hepatic and peripheral insulin resistance. IKK-beta and NF-kappa B provide potential pathogenic

关键词： free fatty acids sodium salicylate oxidative stress insulin resistance hepatic glucose production

Optimization of pretreatment of Jatropha oil with high free fatty acids for biodiesel production

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Frontiers of Chemical Science and Engineering 2012年第2期6卷 210-215页

作者： Supriyono SUWITO Giuliano DRAGONE Hary SULISTYO Bardi MURACHMAN Suryo PURWONO Jose TEIXEIRA Institute for Biotechnology and Bioengineering Centre of Biological Engineering University of Minho Braga 4710-057 Portugal Chemical Engineering Department Gadjah Mada University Yogyakarta 55281 Indonesia

A central composite rotatable design and response surface methodology were used in order to investigate the individual and combined effects of the ethanol-to-oil ratio, H2SO4 concentration, temperature and time of reaction on the reduction of free fatty acid （FFA） in jatropha oil. A quadratic polynomial model relating the reaction variables with FFA reduction was developed, presenting a good coefficient of determination （R2= 0.893）. For reducing FFA to less than 1%, the optimal combination was found to be 0.62 v.v^-1 ethanol-to-oil ratio （14.9 v.v^-1 ethanol-to-FFA ratio）, 1.7% *** H2SO4 concentration, and 79 rain reaction time at a reaction temperature of 54℃. These results are of great relevance to maximize methyl esters formation by transesterification using an alkaline catalyst.

关键词： biodiesel biofuel esterification free fatty acids jatropha curcas oil

The Kinetics of the Esterification of free fatty acids in Waste Cook- ing Oil Using Fe2（SO4）3/C Catalyst

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Chinese Journal of Chemical Engineering 2009年第1期17卷 83-87页

作者：甘孟瑜潘登马利岳恩洪建兵 College of Chemistry & Chemical Engineering Chongqing University Chongqing 400044 China

The esterification of free fatty acids(FFA) in waste cooking oil with methanol in the presence of Fe2(SO4)3/C(ferric sulfate/active carbon) catalyst was *** effects of different temperature,methanol/FFA mole ratio and amount of catalyst on the conversion of FFA were *** results demonstrated that under optimal esterification conditions the final acid value of the resultant system can be reduced to ～1(mg KOH)·g-1,which met fully the requirements in post-treatment for efficient separation of glycerin and *** kinetics of the esterification were also investigated under different *** results indicated that the rate-control step could be attributed to the surface reaction and the esterification processes can be well-depicted by the as-calculated kinetic formula in the range of the experimental conditions.

关键词： biodiesel kinetics esterification free fatty acids waste cooking oil

Yi-Qi-Zeng-Min-Tang,a Chinese medicine,ameliorates insulin resistance in type 2 diabetic rats

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World Journal of Gastroenterology 2011年第8期17卷 987-995页

作者： Zeng Zhang Hong-Li Xue Yi Liu Wen-Jian Wang Institute of Chinese Integrative Medicine Huashan Hospital Fudan University Shanghai 200040 China Institute of Chinese Integrative Medicine Huashan Hospital Fudan University Shanghai 200040 China Institute of Integrated Clinical Medicine Shanghai Academy of Traditional Chinese Medicine YueyangIntegrative Medicine Hospital Shanghai Traditional ChineseMedicine University Shanghai 200437 China

AIM:To investigate the effects of the Chinese herbal decoction,Yi-Qi-Zeng-Min-Tang(YQZMT),on insulin resistance in type 2 diabetic ***:Sprague-Dawley rats were divided into two dietary regiments by feeding either normal pellet diet(NPD) or high fat diet(HFD).Four weeks later,the HFD-fed rats were injected intraperitoneally with lowdose streptozotocin(STZ).Rats with non-fasting blood glucose level ≥ 16.67 mmol/L were considered type 2 diabetic and further divided into five subgroups:the type 2 diabetes model group,low-dose,medium-doseand high-dose YQZMT groups,and rosiglitazone ***-matched NPD-fed rats served as *** or rosiglitazone were administered for 8 *** glucose and insulin tolerance tests were performed before and after the treatment to measure the glucose tolerance and insulin *** levels of biochemical parameters,adipocytokines,such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),as well as free fatty acids(FFAs),were also ***:There was significant elevation of insulin resistance and serum levels of fasting glucose(12.82 ± 1.08 mmol/L vs 3.60 ± 0.31 mmol/L,P < 0.01),insulin(7197.36 ± 253.89 pg/mL vs 4820.49 ± 326.89 pg/mL,P < 0.01),total cholesterol(TC)(8.40 ± 0.49 mmol/L vs 2.14 ± 0.06 mmol/L,P < 0.01),triglyceride(2.24 ± 0.12 mmol/L vs 0.78 ± 0.05 mmol/L,P < 0.01),low-density lipoprotein cholesterol(LDL-c)(7.84 ± 0.51 mmol/L vs 0.72 ± 0.04 mmol/L,P < 0.01) and decrease in high-density lipoprotein cholesterol(HDL-c)(0.57 ± 0.03 mmol/L vs 1.27 ± 0.03 mmol/L,P < 0.01) in the low-dose STZ and high-fat diet induced type 2 diabetic group when compared with the control *** of YQZMT induced dose-and timedependent changes in insulin resistance,glucose and lipid profile,and reduced levels of FFA,TNF-α and IL-6 in the type 2 diabetic *** the treatment,compared with the diabetic group,the insulin resistance was ameliorated in the high-dose YQZMT(2.82 g/100 g per day) group

关键词： Yi-Qi-Zeng-Min-Tang Insulin resistance Type 2 diabetes Lipids Adipocytokines free fatty acids

Curcumin,a Potential Inhibitor of Up-regulation of TNF-alpha and IL-6 Induced by Palmitate in 3T3-L1 Adipocytes through NF-kappaB and JNK Pathway

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Biomedical and Environmental Sciences 2009年第1期22卷 32-39页

作者： SHAO-LING WANG YING LI YING WEN YAN-FENG CHEN LI-XIN NA SONG-TAO LI CHANG-HAO SUN Department of Nutrition and Food Hygiene Harbin Medical University No. 157 Baojian Road Harbin 150081 Heilongjiang China

Objective To investigate the attenuating effect of curcumin, an anti-inflammatory compound derived from dietary spice turmeric （Curcuma longa） on the pro-inflammatory insulin-resistant state in 3T3-L1 adipocytes. Methods Glucose uptake rate was determined with the [3H] 2-deoxyglucose uptake method. Expressions of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） were measured by quantitative RT-PCR analysis and ELISA. Nuclear transcription factor kappaB p65 （NF-r,B p65） and mitogen-activated protein kinase （MAPKs） were detected by Western blot assay. Results The basal glucose uptake was not altered, and curcumin increased the insulin-stimulated glucose uptake in 3T3-L1 cells. Curcumin suppressed the transcription and secretion of TNF-α and IL-6 induced by palmitate in a concentration-dependent manner. Palmitate induced nuclear translocation of NF-kB. The activities of Jun NH2-terminal kinase ONK）, extracellular signal-regulated kinasel/2 （ERKI/2） and p38MAPK decreased in the presence of curcumin. Moreover, pretreatment with SP600125 （inhibitor of JNK） instead of PD98059 or SB203580 （inhibitor of ERKI/2 or p38MAPK, respectively） decreased the up-regulation of TNF-α induced by palmitate. Conelusion Curcumin reverses palmitate-induced insulin resistance state in 3T3-L1 adipocytes through the NF-kB and JNK pathway.

关键词： Curcumin Insulin resistance Inflammation Adipocyte free fatty acids

Hepatic lipid metabolism changes in short-and long-term prehepatic portal hypertensive rats

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World Journal of Gastroenterology 2006年第42期12卷 6828-6834页

作者： Maria-Angeles Aller Elena Vara Cruz García Maria-Paz Nava Alejandra Angulo Fernando Sánchez-Patán Ana Calderón Patri Vergara Jaime Arias SurgeryⅠ Department School of Medicine Complutense University of Madrid Spain Biochemical and Molecular Biology Department School of Medicine Complutense University of Madrid Spain Animal Physiology Department (Physiology Ⅱ) School of Biological Sciences Complutense University of Madrid Spain Physiology Unit. Veterinary School Autonoma University of Barcelona Bellaterra Catalua Spain

AIM: To verify the impairment of the hepatic lipid metabolism in prehepatic portal hypertension. METHODS: The concentrations of free fatty acids, diacylglycerol, triglycerides, and phospholipids were assayed by using D-[U-14C] glucose incorporation in the different lipid fractions and thin-layer chromatography and cholesterol was measured by spectrophotometry, in liver samples of Wistar rats with partial portal vein ligation at short- (1 mo) and long-term (1 year) (i.e. portal hypertensive rats) and the control rats. RESULTS: In the portal hypertensive rats, liver phospholipid synthesis significantly decreased (7.42 ± 0.50 vs 4.70 ± 0.44 nCi/g protein; P free fatty acids (2.08 ± 0.14 vs 3.36 ± 0.33 nCi/g protein; P < 0.05), diacylglycerol (1.93 ± 0.2 vs 2.26 ± 0.28 nCi/g protein), triglycerides (2.40 ± 0.30 vs 4.49 ± 0.15 nCi/g protein) and cholesterol (24.28 ± 2.12 vs 57.66 ± 3.26 mg/g protein; P < 0.01). CONCLUSION: Prehepatic portal hypertension in rats impairs the liver lipid metabolism. This impairment consists in an increase in lipid deposits (triglycerides,diacylglycerol and cholesterol) in the liver, accompanied by a decrease in phospholipid synthesis.

关键词： Portal hypertension free fatty acids Diacylglycerides Triglycerides Phospholipids Cholesterol