Expression and significance of fat mass and obesity associated gene and forkhead transcription factor O1 in non-alcoholic fatty liver disease

Background Non-alcoholic fatty liver disease （NAFLD） is a complex disorder and has been closely linked to obesity.The fat mass and obesity-associated （FTO） gene is a newly discovered gene related to obesity,which enhances oxidative stress and tipogenesis in NAFLD.The forkhead transcription factor O1 （FoxO1） is another important gene involved in NAFLD,which causes lipid disorders when insulin resistance appears in the liver.However,the interactions between FTO and FoxO1 during the pathogenesis of NAFLD have not been fully elucidated.This study was designed to identify the relationship between these two factors that are involved in the development of NAFLD.Methods This study includes two parts referred to as animal and cell experiments.Twelve female SPF C57BL/6 mice were fed a high-fat diet to serve as an NAFLD animal model.Aspartate aminotransferase （AST）,alanine aminotransferase （ALT）,total triglyceride （TG）,total cholesterol （TC）,alkaline phosphatase （ALP）,high-density lipoprotein （HDL）,and low-density lipoprotein （LDL） were measured.Immunohistochemical analysis was used to detect the expression and histological localization of FTO,FoxO1,and adenosine monophosphate （AMP）-activated protein kinase （AMPK）.The L02 cells were exposed to high fat for 24,48,or 72 hours.Oil red O staining was used to detect intracellular lipid droplets.Reverse transcription-polymerase chain reaction was used for analyzing the levels of FTO and FoxO1 mRNA.Results At the end of 10 weeks,ALP,ALT,AST,and LDL were significantly increased （P ＜0.01）,while TC and TG were also significantly higher （P ＜0.05）.In addition,HDL was significantly decreased （P ＜0.05）.The FTO and FoxO1 proteins were weakly expressed in the control group,but both FTO and FoxO1 were expressed significantly higher （P ＜0.01） in the experimental group,and the expression of the two factors was significantly correlated.AMPK in the high-fat group showed a low level of correlation with FTO,but not with FoxO1.Oil Red O staining results showed that the cells cultured in 50％ fetal bovine serum for 24,48,or 72 hours exhibited steatosis.FTO and FoxO1 mRNA were increased in the high-fat group compared with the normal group （P ＜0.01）.The expression levels of FTO and FoxO1 mRNA were the highest at 48 hours （P ＜0.05）.Conclusions A high-fat diet leads to higher expression of FTO,phosphorylation of FoxO1,and decreased phosphorylation of AMPK.These results suggest that the interactions between FTO and FoxO1 are closely related to the pathogenesis of NAFLD.

MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma

Background:Osteosarcoma(OS),recognized as the predominant malignant tumor originating from bones,necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies.The role of fat mass and obesity-associated(FTO)in OS,particularly its correlation with malignant traits,and the fundamental mechanism,remains to be elucidated.Materials and Methods:1.The FTO expression and survival rate in tumors were analyzed.2.FTO in OS cell lines was quantified utilizing western blot and PCR.3.FTO was upregulated and downregulated separately in MG63.4.The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8,colony formation,wound healing,and Transwell assays.5.The expression of miR-150-5p in OS cells-derived exosomes was identified.6.The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay.7.The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated.Results:The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate.Furthermore,the downregulation of FTO significantly impeded the growth and metastasis of OS cells.Additionally,miR-150-5p,which was downregulated in both OS cells and their derived exosomes,was found to bind to the 3′-UTR of FTO through dual luciferase experiments.Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability.Conclusions:We identified elevated levels of FTO in OS,which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes.It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.

Association analysis of FTO gene polymorphisms and obesity risk among Egyptian children and adolescents

Obesity is a common disorder that has a significant impact on human health as it may lead to many serious diseases and sometimes morbidity.Previous genome-wide association studies(GWAS)confirmed that there is a relationship between some variants in the first intron of the fat mass and obesity associated(FTO)gene and obesity in adults and children in different ethnic groups.In our study,the association of the FTO rs9939609 and rs17817449 variants with obesity was investigated in Egyptian children and adolescents.We examined rs9939609 and rs17817449 polymorphisms in 100 control and 100 obese cases,we used the restriction fragment length polymorphism(RFLP)technique to genotype the samples.The current study showed that there were no significant differences(P>0.05)between the cases and controls in both variants of rs17817449 and rs9939609 polymorphisms.However,there were significant correlations between rs17817449 and cholesterol and between rs9939609 and LDL.In Current Study although the two variants(rs9939609 and rs17817449)didn’t show an association with obesity,but there was a correlation between the lipid profile and these two variants.

The association between common genetic variation in the FTO gene and metabolic syndrome in Han Chinese

Background Genome-wide association studies for type 2 diabetes mellitus （T2DM） identified FTO gene as a locus conferring increased risk for common obesity in many populations with European ancestry. However, the involvement of FTO gene in obesity or T2DM related metabolic traits has not been consistently established in Chinese populations. The objective of this study was to investigate the association of FTO genetic polymorphisms with metabolic syndrome （MetS） in Han Chinese. Methods We tested 41 FTO single nucleotide polymorphisms （SNPs） for association between FTO and MetS-related traits. There were a total of 236 unrelated subjects （108 cases and 128 controls）, grouped according to the International Diabetes Federation （IDF） criteria. Results Of the 41 SNPs examined, only SNP rs8047395 exhibited statistical significance （P=-0.026） under a recessive model, after Bonferroni adjustment for multiple testing （OR 1.64, 95% CI 1.11-2.42; P=-0.014）. The common distributions of this polymorphism among Chineseawith a minor allele frequency （MAF） of 36% in the control group versus 48% in the Met$ group--greatly improved our test power in a relatively small sample size for an association study. Previously identified obesity- （or T2DM-） associated FTO SNPs were less common in Hart Chinese and were not associated with MetS in this study. No significant associations were found between our FTO SNPs and any endophenotypes of MetS. Conclusions A more common risk-conferring variant of FTO for MetS was identified in Han Chinese. Our study substantiated that genetic variations in FTO locus are involved in the pathogenesis of MetS.