Non-invasive means of measuring hepatic fat content

Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography (CT), magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS) can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance (MR) techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo 1H MRS is a fast, safe, non-invasive method forthe quantification of intrahepatocellular lipid (IHCL) levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis (e.g. non-alcoholic fatty liver disease), or in testing new treatments for these conditions.

Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

Genetic susceptibility to metabolic associated fatty liver disease(MAFLD)is complex and poorly characterized.Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors.We performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FLI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics Lifelines Initiative(UGLI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3L1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPLA3,TM6SF2,and APOE.GWAS of FLI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGLI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FLI(UGLI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3L1 and GCM1)were replicated in the FLI GWAS.We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI.Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI,a substantial similar genetic architecture was found.FLI is identified as an easy and reliable approach to study hepatic fat content at the population level.

How to select the quantitative magnetic resonance technique for subjects with fatty liver:A systematic review

BACKGROUND Early quantitative assessment of liver fat content is essential for patients with fatty liver disease.Mounting evidence has shown that magnetic resonance(MR)technique has high accuracy in the quantitative analysis of fatty liver,and is suitable for monitoring the therapeutic effect on fatty liver.However,many packaging methods and postprocessing functions have puzzled radiologists in clinical applications.Therefore,selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging.AIM To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver.METHODS We completed a systematic literature review of quantitative MR techniques for detecting fatty liver,following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol.Studies were retrieved from PubMed,Embase,and Cochrane Library databases,and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria.The Reference Citation Analysis database(https://www.referencecitationanalysis.com)was used to analyze citation of articles which were included in this review.RESULTS Forty studies were included for spectroscopy,two-point Dixon imaging,and multiple-point Dixon imaging comparing liver biopsy to other imaging methods.The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed.CONCLUSION The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression.

Dihydromyricetin improves liver fat deposition in high-fat diet-induced obese mice

It has been reported that the histone/protein deacetylase SIRT1-AMP-activated protein kinase(SIRT1-AMPK)signaling pathway may play a role in the effects of dihydromyricetin(DHM)on improving triglyceride(TG)accumulation and insulin resistance in liver cells.Therefore,we aimed to further observe the effect of DHM on liver fat deposition in high-fat diet(HFD)-induced obese mice and explore its possible mechanism.C57BL/6J mice were fed with a normal diet(ND)and HFD and were treated with or without low-dose(125 mg/kg)or high-dose(250 mg/kg)DHM for 16 weeks,respectively.During the experiment,body weight was checked every 2 weeks.After 16 weeks,the orbital vein was bled,the animals were sacrificed,and the subscapular,epididymal,and inguinal fat were collected and weighed with an electronic scale.An automatic biochemical analyzer was used to determine the levels of serum triglyceride(TG),serum total cholesterol(TC),serum high-density lipoprotein(HDL),and serum low-density lipoprotein(LDL).The livers were stained with hematoxylin-eosin staining(H&E)and Oil Red O to detect liver fat deposition.A colorimetric method was used to detect liver MDA and SOD contents.Quantitative real-time PCR(q RT-PCR)was used to detect the gene expressions of related indicators,such as interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor-α(TNF-α),acetyl-Co A carboxyl acetyl-Co A carboxylase(ACC),sterol regulatory element-binding protein-1c(SREBP-1),fatty acid synthetase(FAS),peroxisome proliferator activation receptor alpha(peroxisome proliferator-activated receptor-alpha,PPARα),palmitoyltransferase 1(carnitine palmitoyltransferase 1,CPT1),SIRT1,and AMPK.Western blotting analysis was used to detect the protein expression levels of SIRT1,AMPK,SIRT1-AMPK,ACC,SREBP-1,FAS,PPARα,and CPT1.Results showed that compared with the ND group,the weight and body fat of the mice in the HFD group were increased significantly.The levels of TG,TC,and LDL were increased,the level of HDL was decreased,the volume of hepatocytes was increased,the number of lipid droplets,fat deposition,MDA,IL-6,IL-8,TNF-α,SREBP-1c,FAS,ACC1,SIRT1,and AMPK protein levels were significantly increased,and the SOD activity,PPARα,CPT1,SIRT1 m RNA,AMPK m RNA,PPARα,CPT1 levels were significantly decreased.DHM could significantly reverse the changes of the above indexes in HFD mice,while DHM had no significant effect on the above indexes in ND mice.Collectively,our findings revealed that DHM improved liver fat deposition in HFD-induced obese mice,and the mechanism might be related to inhibition of oxidative stress,inflammation,lipid synthesis,and promotion of lipid decomposition.