USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells

Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and FFA.USP19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation assays.Cell cycle distribution and apoptosis were detected by flow cytometry.The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and IB.Results In HG+FFA-challenged HK-2 cells,USP19 was highly expressed.USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells.Moreover,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 cells.Mechanistically,USP19 stabilized the TAK1 protein through deubiquitination.Importantly,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells.Conclusion The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.AIM To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.METHODS A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and NAFLD.External validation encompassed 172 participants.NAFLD patients were divided based on liver fibrosis scores.The analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.RESULTS Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific BAs.In UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative correlation.Levels ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in NAFLD.The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.CONCLUSION This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.

Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E_2 and cytokines

AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.

Fatty Acid Synthase and Hormone-sensitive Lipase Expression in Liver Are Involved in Zinc-α2-glycoprotein-induced Body Fat Loss in Obese Mice

Objective To explore the effects of zinc-0t2-glycoprotein （ZAG） on body weight and body fat in high-fat-diet （HF1））-induced obesity in mice and the possible mechanism. Methods Thirty-six male mice were fed with standard food （SF） （n=9） and HFD （n=27）, respectively. Five weeks later, 9 mice fed with HFD were subjected to ZAG expression plasmid DNA transfection by liposome transfection method, and another 9 mice to negative control plasmid transfection. Two weeks later, serum ZAG level in the mice was assayed by Western blot, and the effects of ZAG over-expression on body weight, body fat, serum biochemical indexes, and adipose tissue of obese mice were evaluated. The mRNA expressions of fatty acid synthase （FAS） and hormone sensitive lipase （HSL） in liver tissue were deterlnined by reverse transcription-polymerase chain reaction. Results Serum ZAG level significantly lowered in simple HFD-fed mice in comparison to SF-fed mice （0.51±0.10 AU vs. 0.75±0.07 AU, P〈0.01）. Further statistical analysis demonstrated that ZAG level was negatively correlated with body weight （r =-0.56, P〈0.001）, epididymal fat mass （r=-0.67, P〈O. 001）, percentage of epididymal fat （r= 0.65, P〈0.001）, and increased weight （r= 0.57, P〈0.001） in simple SF- and HFD fed mice. ZAG over-expression in obese mice reduced body weight and the percentage of epididyreal fat. Furthermore, FAS mRNA expression decreased （P〈0.01） and HSL mRNA expression increased （P〈0.001） in the liver in ZAG over-expressing mice. Conclusions ZAG is closely related to obesity. Serum ZAG level is inversely correlated with body weight and percentage of body fat. The action of ZAG is associated with reduced FAS expression and increased HSL expression in the liver of obese mice.

Free fatty acids receptors 2 and 3 control cell proliferation by regulating cellular glucose uptake

BACKGROUND Colorectal cancer(CRC)is a worldwide problem,which has been associated with changes in diet and lifestyle pattern.As a result of colonic fermentation of dietary fibres,short chain free fatty acids are generated which activate free fatty acid receptors(FFAR)2 and 3.FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells.Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis.AIM To understand the role of short chain FFARs in CRC.METHODS Transcriptome analysis console software was used to analyse microarray data from CRC patients and cell lines.We employed short-hairpin RNA mediated down regulation of FFAR2 and FFAR3 genes,which was validated using quantitative real time polymerase chain reaction.Assays for glucose uptake and cyclic adenosine monophosphate(cAMP)generation was done along with immunofluorescence studies to study the effects of FFAR2/FFAR3 knockdown.For measuring cell proliferation,we employed real time electrical impedancebased assay available from xCELLigence.RESULTS Microarray data analysis of CRC patient samples showed a significant down regulation of FFAR2 gene expression.This prompted us to study the FFAR2 in CRC.Since,FFAR3 shares significant structural and functional homology with FFAR2,we knocked down both these receptors in CRC cell line HCT 116.These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of glucose transporter 1.Since,FFAR2 and FFAR3 signal through G protein subunit(Gαi),knockdown of these receptors was associated with increased cAMP.Inhibition of protein kinase A(PKA)did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway.CONCLUSION Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of PKA mediated cAMP signalling.Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes.This study paves the way to understand the mechanism of action of short chain FFARs in CRC.

Genetic Variants in the ELOVL5 but not ELOVL2 Gene Associated with Polyunsaturated Fatty Acids in Han Chinese Breast Milk

The present study was designed to examine the contributions of the fatty acid elongase （ELOVL） gene polymorphisms to the levels of polyunsaturated fatty acids （PUFAs） in breast milk. Two hundred and nine healthy Han Chinese mothers were included in the study. Carriers of minor alleles of SNPs （rs2397142 and rs9357760） in ELOVL5 were associated with higher levels of linoleic acid （LA）, dihomo-γ-linolenic acid （DGLA）, arachidonic acid （AA）, docosatetraenoic acid （DTA）, docosahexenoic acid （DHA）, while in rs209512 of ELOVL5 the carriers of minor alleles had lower levels of DTA compared to major homozygote alleles （P ranged from 0.004-0.046）, and genetically explained variability ranged from 3.2% for eicosapentaenoic acid （EPA） to 6.0% for LA. Our findings demonstrated that common variation in ELOVL5 gene encoding rate-limiting enzymes in the metabolism of PUFAs contribute to the PUFAs in breast milk.

High-starchy carbohydrate diet aggravates NAFLD by increasing fatty acids influx mediated by NOX2

Nonalcoholic fatty liver disease(NAFLD)is a high-incidence lipid disorder that affects more than a quarter of the population worldwide,and dietary intervention is the recognized treatment.Starch is the main component of staple foods that are consumed daily,and the effects,metabolic pathway,and molecular mechanism of starch in the context of NAFLD remain unclear.Our study showed that a high-starch carbohydrate diet(HCD)led to the occurrence and exacerbation of NAFLD in mice.Transcriptomics and metabonomic analyses showed that the increased fatty acid influx mediated by NADPH oxidase 2(NOX2)exacerbated NAFLD.Knocking down NOX2 specifically alleviated HCD-induced NAFLD in vivo and in vitro.Moreover,the large amounts of ROS produced by NOX2 further exacerbated insulin resistance and increased lipolysis in perirenal white adipose tissue(periWAT),thereby providing fatty acids for hepatic lipid synthesis.In addition,the interaction between AMPKα1 and p47phox was the pathway that mediated the high expression of NOX2 induced by a HCD.Our study systematically demonstrated the effect of a HCD on NAFLD.Elevated fatty acid influx is a unique molecular regulatory pathway that mediates HCD-induced NAFLD exacerbation,which is different from the effect of simple sugars.Additionally,NOX2 was suggested to be a specific and effective drug target for NAFLD.

Effect of diacylglycerol acyltransferase 2overexpression in 3T3-L1 is associated to an increase in mono-unsaturated fatty acid accumulation

Background：Fatty acid（FA） composition is the most important parameter affecting the flavor and nutritional value of the meat.The final and the only committed step in the biosynthesis of triglycerides is catalyzed by diacylglycerol acyltransferase 2（DGAT2）.The role of DGAT2 in lipid accumulation has been demonstrated in adipocytes,However,little is known about the effect of DGAT2 on the FA composition of these cells.Methods：To investigate the role of DGAT2 in regulating lipid accumulation,FA composition and the expression of adipogenic genes,we cloned the open reading frame of the porcine DGAT2 gene and established 3T3-L1 cells that overexpressed DGAT2.Cells were then cultured in differentiation medium（DM） without FA,with a mixture of FAs（FA-DM）,or containing a ^（13）C stable isotope-labeled FA mixture（IFA-DM）.The FA composition of adipocytes was analyzed by gas chromatography-mass spectrometry and gas chromatography-isotope ratio mass spectrometry.Quantitative PCR and western blotting were employed to detect expression of adipogenic genes in 3T3-L1 adipocytes cultured with FA-DM for 12 d.Results：The triacylglyceride（TAG） content was significantly higher in 3T3-L1 adipocytes overexpressing DGAT2 than in control cells.When cultured in DM or FA-DM for 12 d,cells overexpressing DGAT2 showed a higher proportion of unsaturated FAs（C16：1 and C18：1）.However,when cells overexpressing DGAT2 were cultured with FA-DM for30 min,the FA composition was almost identical to that of controls.Further,the proportion of stable isotope-labeled FAs were similar in 3T3-L1 adipocytes overexpressing DGAT2 and control cells cultured in IFA-DM for 12 d.These results collectively indicate that the higher proportion of mono-unsaturated FAs,C16：1 and C18：1,may originate from de novo FA synthesis but not from the uptake of specific FAs from the medium.This hypothesis is further supported by evidence that both mRNA and protein expression of genes involved in FA synthesis（ACACA,FASN,SCD1,and A-FABP）were significantly higher in cells overexpressing DGAT2 than in control cells.Conclusions：In conclusion,our study revealed that TAG accumulation,the proportion of MUFAs,and the expression of adipogenic genes were higher in 3T3-L1 cells overexpressing DGAT2 than in control cells.

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

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 levels.This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities,which led to type 2 diabetes.However,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 flexibility.These data favor a FFA-glucose-insulin axis.The 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.

Association of Bovine Fatty Acid Desaturase 2 Gene Single-Nucleotide Polymorphisms with Intramuscular Fatty Acid Composition in Japanese Black Steers

Beef from Japanese Black cattle (JBK), is popular in Japan and valued for its highly marbled fat content. In JBK, genes affecting oleic acid content in meat have been studied mainly to lower the fat melting point and improve tenderness;however, there has been no direct correlation demonstrated between beef taste and oleic acid. To investigate genes affecting other fatty acids other than oleic acid, polymorphisms of the fatty acid desaturase 2 (FADS2) gene were genotyped and associations with fatty acid profile in JBK beef were investigated. Amplifications of 5’-flanking regions, 12 exons, and 3’-untranslated regions of the FADS2 gene in three Japanese and five Western cattle breeds via PCR, were amplified, sequenced and SNPs were identified using specific TaqMan genotyping assay. Fatty acid composition of intramuscular adipose tissue of the Trapezius muscle was analyzed in JBK steers. Six of the 15 identified SNPs are novel and have never been registered in any public bovine SNP database. A non-synonymous SNP (rs211580559;C > T;294 Ala > Val) in exon 7 was examined in order to evaluate its association with fatty acid profiles. The data showed that highly significant association existed between rs211580559 and C18:2 (n-6) composition, and accounted for 22.3% of the variation. There were no significant relationships between rs2115-80559 and the other fatty acids. It was concluded that rs211580559 of the FADS2 gene may be a useful selection marker for reducing unfavorable volatiles generated from linoleic acid in JBK beef during the cooking process.

Comparison of the fatty acid composition of the serum phospholipids of controls, prediabetics and adults with type 2 diabetes

Objective: Although abnormalities in the fatty acid composition of serum and red cell membrane phospholipids of patients with type 2 diabetes are well-documented, lacking are studies of this issue in prediabetic individuals. Materials/Methods: For this cross-sectional study, we recruited 180 subjects (30 - 80 years), 56 of whom were normal with regard to glucose control (HbA1c, 6.5%). Serum phospholipids were isolated and analyzed for fatty acids. Results: Most importantly, the fatty acid compositions of the controls and prediabetic subjects were not different for 19 fatty acids. However, the fatty acid profile of the phospholipids of the patients with diabetes differed from the other two groups;the 14 to 18-carbon saturated fatty acids were decreased by 12% - 26% whereas the unsaturated fatty acids 16:1n-7, 18:1n-9, 18:2n-6, 20:3n-6 and 20:4n-6 were increased by 45% - 64%. Of note, the docosahexaenoic acid (DHA) status of individuals in all three study groups was remarkably low compared with international values, as indicated by DHA proportions in the 1.62% - 2.07% range, and there were no differences between groups. The mean melting point of the phospholipid fatty acids of the diabetic patients (32.2℃) was significantly lower (p < 0.001) than that of the prediabetic subjects (38.1℃) and the controls (39.9℃) which were not different from each other. Conclusion: These observations indicate that the fatty acid changes associated with type 2 diabetes follow the onset of the disease as opposed to being a causative factor of poor glucose control and insulin insensitivity.

Type 2 diabetes with good glycemic control have improved insulin response and lower non-esterified fatty acid level after a meal challenge

Background: Pathogenesis of type 2 diabetes (T2DM) involves defects in β-cell function with impaired first and second phase insulin response, and reduced insulin sensitivity. Diabetic dyslipidemia is an important and common risk factor for coronary heart disease (CHD). Aims: This study examined the effect of glycemic control on post prandial insulin and lipid parameters in response to a standardised meal challenge among Type 2 diabetes patients with good and poor glycemic control. Methods: We cross-sectionally studied 31 T2DM patients with good glycemic control and 32 T2DM patients with poor glycemic control. Subjects were given, after minimum 10 hours of fasting, a standard meal containing 58% fat. Fasting and serial postprandial blood samples were taken over 8 hours to determine levels of triglyceride, direct LDL-C, apoB lipoprotein, non-esterified-fatty-acid, insulin and blood glucose. Results: Post prandial NEFA was significantly higher in poor controlled diabetes patients compared to good control diabetes patients (p = 0.019), and post-hoc analysis showed significant difference from 3 hours post prandial to 4 hours post prandial, where p= 0.021. Although the difference in insulin between the 2 groups did not reach statistical significance (p =0.058), post-hoc analysis showed significant difference between the 2 groups from fasting to 1 hour post prandial (p = 0.034) despite postprandial glucose being significantly higher in poor controlled diabetes patients (p < 0.001), throughout the postprandial period. Conclusion: T2DM patients with good glycemic control have improved insulin response with lower non-esterified fatty acid.

Relationship between Ethanol and 2-phenylethanol Stress Tolerance and Fatty Acid Compositions of Saccharomyces cerevisiae

In the present study, we investigated of the ethanol （Eth）, 2-phenylethanol （2-PE） and ethanol/2-phenylethanol （Eth/2-PE） stress tolerance and established relationship between stress tolerance and fatty acid compositions of wine yeast strain S. cerevisiae UCM Y-524 in relation to different cultivation factors. Changes in cell membrane fatty acid profiles studied under different temperature and media. The active oxygenation, semi-aerobic cultivation supplemented Tween 80 conditions were used in different combinations. The concentrations of 2-PE and Eth, the fatty acids methyl esters （FAMES） in the media were measured by GC-MS analyses. 2-PE, Eth, FAMES were identified by NIST02 MS database at the 2-PE and Eth standard solution （Merck, Germany）, bacterial FAMES standard （Supelco）. Palmitoleic and oleic acid were dominated for S. cerevisiae UCM Y-524. The unsaturated/saturated fatty acid （UFA/SFA） ratio was higher than five for S. cerevisiae UCM Y-524 at 14 ~C in simple medium and about more than three for other conditions. It has been found that yeast cells grown in the presence of the 2-PE, Eth and Eth/2-PE appear to increase the amount of unsaturated fatty acids, especially oleic acid, in cellular lipids especially under active oxygenation supplemented with Tween 80. S. cerevisiae UCM Y-524 has a higher tolerance under 2-PE, Eth and Eth/2-PE stress at 28 ~C in a simple medium under aerobic conditions. A higher concentration of unsaturated fatty acids in the membrane S. cerevisiae UCM Y-524 and a lower temperature under aerobic conditions, has been considered to have a positive influence on the excretion of 2-phenylethanol.

Correlation of serum free fatty acid content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus

Objective: To investigate the correlation of serum free fatty acid content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Methods: A total of 189 patients with type 2 diabetes mellitus who were treated in this hospital between August 2015 and February 2018 were chosen as type 2 diabetes mellitus group, and 100 healthy subjects who received physical examination in this hospital during the same period were chosen as the normal control group. The differences in serum levels of FFA, glucolipid metabolism indexes, microinflammation indexes and oxidative stress indexes were compared between the two groups of subjects, and correlation analysis was adopted to judge the inner link of serum FFA content with glucolipid metabolism, microinflammation and oxidative stress state in patients with type 2 diabetes mellitus. Results: Serum FFA content of type 2 diabetes mellitus group was higher than that of control group;serum glucolipid metabolism indexes FPG, 2hPG, TC and LDL-C levels were higher than those of normal control group whereas HDL-C level was lower than that of control group;serum microinflammation indexes IL-1β, IL-6, IL-10, IL-15 and TNF-α contents were higher than those of control group;serum oxidative stress indexes GSH-Px and SOD contents were lower than those of control group whereas ROS and MDA contents were higher than those of control group. Pearson test showed that the serum FFA content of patients with type 2 diabetes mellitus was directly correlated with the contents of glucolipid metabolism, microinflammation and oxidative stress indexes. Conclusion: Serum FFA content significantly increases in patients with type 2 diabetes mellitus, and the specific content was directly correlated with glycolipid metabolism, microinflammation, oxidative stress and other illness indexes.

Effect of Nb_(2)O_(5)·nH_(2)O Termal Treatment on the Esterification of a Fatty Acid

In general, esterification reactions are favored by the increase in reaction temperature, excess of one of the reactants (usually alcohol), and additions of acid or basis catalysts. Esterification of oleic acid with methanol catalyzed by Nb2O5·nH2O calcined at different temperatures showed good conversion rates, especially at reaction temperature of 100°C and higher catalyst proportions. PLS calibration showed good results for predicting the amounts of methyl oleate in reaction products.

苍柴调中方辅助改善肝郁脾虚型肥胖2型糖尿病的疗效及对胰岛素抵抗、FFA、LDL-C水平的影响

目的:探讨苍柴调中方辅助改善肝郁脾虚型肥胖2型糖尿病(T2DM)的疗效,并分析其对胰岛素抵抗、游离脂肪酸(FFA)、低密度脂蛋白胆固醇(LDL-C)水平的影响。方法:选取2020年4月至2023年4月该院收治的肝郁脾虚型肥胖T2DM患者100例,根据随机数字表法分为两组,各50例。对照组患者使用二甲双胍治疗,观察组患者在对照组基础上联合苍柴调中方辅助治疗。观察两组患者的治疗效果,比较两组患者治疗前后中医症状积分、糖代谢指标[空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)]、血清FFA、LDL-C、肿瘤坏死因子α(TNF-α)水平的差异,并对不良反应发生率进行统计。结果:观察组患者的治疗总有效率高于对照组,不良反应发生率低于对照组,差异均有统计学意义(P<0.05)。治疗后,观察组患者倦怠乏力、精神抑郁、脘腹闷胀及大便黏滞等中医症状积分均低于对照组,差异均有统计学意义(P<0.05)。与治疗前比较,两组患者治疗后的FBG、HOMA-IR、FINS水平均明显降低,其中观察组患者治疗后的FINS、FBG及HOMA-IR水平低于对照组,差异均有统计学意义(P<0.05)。观察组患者治疗后的血清LDL-C、FFA、TNF-α水平均低于对照组,差异均有统计学意义(P<0.05)。结论:苍柴调中方辅助治疗可明显提高肝郁脾虚型肥胖T2DM患者的治疗效果,改善胰岛素抵抗,下调血清FFA、LDL-C水平。

2型糖尿病伴干眼症病人血清和泪液分泌型卷曲相关蛋白5、脂肪酸结合蛋白4水平与病情严重程度的相关性

目的分析分泌型卷曲相关蛋白5(SFRP-5)、脂肪酸结合蛋白4(FABP4)在2型糖尿病(T2DM)伴干眼症病人血清和泪液中的表达及其与病情严重程度的相关性。方法选取2020年12月至2021年12月唐山市眼科医院收治的T2DM病人145例,其中单纯T2DM病人84例168眼(T2DM组),伴干眼症病人61例122眼(T2DM伴干眼症组),另选取同期该院体检健康者50例100眼作为对照组。T2DM伴干眼症病人又分为轻度组(29例)、中度组(17例)、重度组(15例)。利用酶联免疫吸附法测定所有受试者血清和泪液中SFRP-5、FABP4水平;相关性分析采用Pearson法或Spearman法;logistic回归分析影响T2DM病人干眼症发生的因素。结果T2DM伴干眼症组、T2DM组血清和泪液SFRP-5水平均低于对照组(106.09±8.37、135.72±9.26比158.34±9.45,28.85±5.13、58.27±6.14比45.18±5.92),T2DM伴干眼症组低于T2DM组(P<0.05);T2DM伴干眼症组、T2DM组血清和泪液FABP4水平均高于对照组(70.63±6.59、58.27±6.14比45.18±5.92,15.91±3.76、10.28±3.58比7.72±3.29),T2DM伴干眼症组高于T2DM组(P<0.05)。重度组、中度组血清和泪液SFRP-5水平(68.29±7.15、95.54±8.34比131.82±9.02,12.83±4.62、24.72±5.49比39.56±5.18)、泪膜破裂时间(BUT)、泪液分泌试验(SIT)低于轻度组,重度组低于中度组(P<0.05);重度组、中度组血清和泪液FABP4水平(84.56±6.83、73.18±6.94比61.93±6.27,25.64±4.19、17.15±3.86比10.16±3.47)及眼表疾病指数量表(OSDI)积分高于轻度组,重度组高于中度组(P<0.05)。T2DM伴干眼症病人血清与泪液SFRP-5水平呈正相关,血清与泪液FABP4水平也呈正相关(P<0.05)。T2DM伴干眼症病人血清和泪液SFRP-5水平与OSDI积分均呈负相关,与BUT、SIT均呈正相关(P<0.05);血清和泪液FABP4水平与OSDI积分均呈正相关,与BUT、SIT均呈负相关(P<0.05)。血清和泪液SFRP-5水平是影响T2DM病人干眼症发生的独立保护因素,而血清和泪液FABP4水平是独立危险因素(P<0.05)。结论SFRP-5在T2DM伴干眼症病人血清和泪液中均低表达,FABP4均高表达,二者与病情严重程度密切相关。

视网膜静脉阻塞患者血清FABP4,VWF和LCN-2水平表达与继发黄斑水肿程度及预后的关系研究

目的 探究视网膜静脉阻塞(retinal vein obstruction,RVO)患者血清脂肪细胞型脂肪酸结合蛋白(fatty acid-binding protein 4,FABP4)、血管性假血友病因子(von willebrand factor,VWF)、脂质运载蛋白2(lipocalin-2,LCN-2)水平表达与继发黄斑水肿(macular edema,ME)程度及预后的关系研究。方法 选取2021年1月~2023年8月来西北大学附属第一医院治疗的98例确诊的RVO继发ME患者为观察组,根据黄斑水肿程度分为重度组(n=46)、中度组(n=32)和轻度组(n=20),根据预后情况分为预后不良组(n=36)和预后良好组(n=62);另选取98例单纯RVO患者为对照组。比较各组血清FABP4,VWF,LCN-2水平;多因素Logistic回归分析RVO继发ME患者发生预后不良的影响因素;ROC曲线分析血清FABP4,VWF和LCN-2水平对RVO继发ME患者发生预后不良的预测价值。结果 与对照组相比,观察组血清FABP4(35.24±4.43 ng/ml vs 23.19±3.69 ng/ml),VWF(2.67±0.67 ng/ml vs1.48±0.38 ng/ml),LCN-2(112.53±12.74 mg/L vs 85.49±9.86 mg/L)水平明显升高,差异具有统计学意义(t=20.690,15.294,16.616,均P<0.05);随病情逐渐发展,轻、中、重度组血清FABP4(33.38±4.29 ng/ml,35.79±4.49 ng/ml,38.64±4.65 ng/ml),VWF(2.36±0.59 ng/ml,2.72±0.66 ng/ml,3.29±0.87 ng/ml),LCN-2(105.84±12.24 mg/L,114.61±12.88 mg/L,124.59±13.69 mg/L)水平逐渐升高,差异具有统计学意义(F=10.194,13.294,15.703,均P<0.05);与预后良好组相比,预后不良组血清FABP4(39.64±4.59 ng/ml vs 32.69±4.34 ng/ml),VWF(3.26±0.87ng/ml vs 2.33±0.55 ng/ml),LCN-2(124.56±13.42 mg/L vs 105.54±12.34 mg/L)水平明显升高,差异具有统计学意义(t=7.482,6.487,7.122,均P<0.05));血清FABP4(OR=2.236,95%CI:1.109~4.510),VWF(OR=2.069,95%CI:1.044~4.100),LCN-2(OR=1.875,95%CI:1.015~3.463)为RVO继发ME患者发生预后不良的独立危险因素(均P<0.05);血清FABP4,VWF,LCN-2水平预测患者发生预后不良的AUC(95%CI)分别为0.817(0.726~0.888),0.791(0.697~0.867)和0.798(0.705~0.872),三者联合预测的AUC为0.932(0.863~0.973),三者联合预测优于各因子单独预测(Z=2.034,2.375,2.385,P=0.042,0.018,0.017)。结论 RVO继发ME患者血清FABP4,VWF和LCN-2水平均上调,且均为患者发生预后不良的独立危险因素,三者联合检测对RVO继发ME患者发生预后不良具有更高的预测价值。

2型糖尿病合并代谢综合征患者血清CTRP9、A-FABP水平变化及临床意义

目的研究2型糖尿病(T2DM)合并代谢综合征(MS)(T2DM~MS)患者血清补体C1q肿瘤坏死因子相关蛋白(CTRP9)、脂肪型脂肪酸结合蛋白(A-FABP)水平变化及临床意义。方法前瞻性选择2021年1月至2023年12月于广西医科大学第二附属医院治疗的90例T2DM患者纳入研究组,根据是否合并MS将其分为T2DM~MS组(n=71)、T2DM未合并MS组(n=19)。将同期于广西医科大学第二附属医院进行体检的90名健康者纳入对照组。检测并比较研究组与对照组、T2DM~MS组与T2DM未合并MS组的糖脂代谢指标[空腹血糖、高密度脂蛋白(HDL-C)、总胆固醇、低密度脂蛋白(LDL-C)、甘油三酯]及血清CTRP9、A-FABP水平。采用Pearson相关性分析CTRP9、A-FABP与各糖脂代谢指标的相关性;采用受试者操作特征(ROC)曲线评价CTRP9、A-FABP对T2DM~MS的诊断效能。结果研究组的空腹血糖、总胆固醇、LDL-C、甘油三酯及血清A-FABP水平分别为(9.37±0.95)mmol/L、(4.38±0.45)mmol/L、(2.83±0.29)mmol/L、(1.58±0.17)mmol/L、(15.48±1.72)ng/mL,均高于对照组,研究组HDL-C及血清CTRP9水平分别为(1.23±0.14)mmol/L、(8.38±0.85)ng/mL,均低于对照组,差异均有统计学意义(P<0.05)。T2DM~MS组空腹血糖、总胆固醇、LDL-C、甘油三酯及血清A-FABP水平分别为(10.26±1.32)mmol/L、(4.51±0.47)mmol/L、(3.15±0.33)mmol/L、(1.74±0.20)mmol/L、(18.21±2.06)ng/mL,均高于T2DM未合并MS组,T2DM~MS组HDL-C及血清CTRP9水平分别为(1.12±0.13)mmol/L、(7.26±0.75)ng/mL,均低于T2DM未合并MS组,差异均有统计学意义(P<0.05)。经Pearson相关分析,血清CTRP9水平与空腹血糖、总胆固醇、LDL-C、甘油三酯均呈负相关(r=-0.902、-0.780、-0.745、-0.753;均P<0.05),与HDL-C呈正相关(r=0.827,P<0.05);血清A-FABP水平与空腹血糖、总胆固醇、LDL-C、甘油三酯均呈正相关(r=0.843、0.812、0.839、0.722;均P<0.05),与HDL-C呈负相关(r=-0.768,P<0.05)。经ROC曲线分析,血清CTRP9联合A-FABP对T2DM~MS的诊断效能高于两者单独诊断。结论T2DM~MS患者血清CTRP9水平低表达,A-FABP水平高表达,血清CTRP9、A-FABP水平与糖脂代谢指标密切相关。血清CTRP9联合A-FABP可提高T2DM~MS的诊断效能,监测血清CTRP9、A-FABP水平有助于预测T2DM~MS的发生。

脂肪酸结合蛋白4在2型糖尿病肾病中的诊断价值

目的:探讨2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清脂肪酸结合蛋白4(fatty acid-binding protein 4,FABP4)与糖尿病肾病(diabetic nephropathy,DN)的相关性及其作为DN早期诊断的应用价值。方法:纳入T2DM患者218例及健康体检者(对照组)20名,收集受试者的一般临床资料如身高、体质量、腰围、糖尿病病程等,计算BMI;收集血糖、糖化血红蛋白、空腹胰岛素、空腹C肽、肝肾功能、血脂等指标,计算稳态模型胰岛素抵抗指数(homeostasis model assessment-insulin resistance index,HOMA-IR)。采用ELISA测定血清FABP4水平;采用联合血肌酐(serum creatinine,Scr)和胱抑素C(cystatin C,Cys C)的慢性肾脏病流行病学协作方程式计算肾小球滤过率;测定尿白蛋白和肌酐水平,计算尿微量蛋白与肌酐比值(urinary albumin to creatinine ratio,UACR)。根据估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)水平将T2DM患者分为肾功能正常组(eGFR≥90 mL/min/1.73 m^(2))、轻度肾功能不全组(eGFR 60~<90 mL/min/1.73 m^(2))和中度肾功能不全组(eGFR 30~<60 mL/min/1.73 m^(2));根据UACR水平分为正常蛋白尿组(UACR<30 mg/g)、微量蛋白尿组(UACR 30~<300 mg/g)和大量蛋白尿组(UACR≥300 mg/g)。采用回归分析评估FABP4与eGFR、UACR严重程度的相关性。结果:(1)与对照组相比,T2DM患者的血清FABP4显著升高。(2)在根据eGFR分层的3个亚组中,随着eGFR的下降,血清FABP4水平显著增加(P<0.001)。但在UACR亚组中差异无统计学意义(P=0.382)。(3)Spearman相关分析显示FABP4与eGFR呈负相关(r=-0.203,P=0.001),与UACR无相关性(r=0.130,P=0.055)。(4)多元线性回归表明,FABP4与eGFR呈独立负相关(r=-0.211,P<0.001),与UACR无相关性(r=-0.047,P=0.534)。(5)ROC曲线显示FABP4诊断DN的最佳截断值为103.9μg/L,AUC为0.745(灵敏度51.2%,特异度92.7%)。结论:T2DM患者血清FABP4水平升高与DN发生发展相关,有可能作为DN早期诊断的生物标志物。