Fat Accumulation In Liver Research Articles

Non-invasive imagistic techniques of diagnostic of hepatical steatosis

Introduction. Fatty liver disease (FLD) is defined as the accumulation of liver fat (hepatic steatosis) in >5% of hepatocytes with or without inflammation and fibrosis. Quantitative imaging techniques can provide objective continuous metrics associated with liver fat content and be recorded for comparison when patients receive check-ups to evaluate changes in liver fat content. The aim of the study was to identify the accuracy of non-invasive imaging techniques in diagnostic FLD. Material and Methods. A total of 1034 studies were identified on the PubMed database. After removing duplicates, 728 titles, and abstracts were screened. Analysed correlation between histopathologically confirmed steatosis and imaging techniques. Results. Controlled attenuation parament (CAP), ATI Attenuation imaging (ATI), Attenuation measurement function (ATT), and Hepatorenal index were analyzed. CAP is the first method based on attenuation of the ultrasound beam, but the limitations of this method are caused by the impossibility to determine the exact location of the region of interest. ATT and ATI have been developed to improve this situation, and these metrics can be used to evaluate the degree of fatty liver on grayscale ultrasonography in real-time with a correct region of interest.CAP showed suboptimal performance in quantifying liver fat content, especially in mild steatosis, which limited its use as a golden standard. Conclusions. Greyscale ultrasound has limited diagnostic performance in mild steatosis. The CAP method is more difficult to be used in overweight and obese patients, but these are the most common patients in FLD. ATT/ATI are the universal methods.

Positive Impacts of Aphanizomenon Flos Aquae Extract on Obesity-Related Dysmetabolism in Mice with Diet-Induced Obesity.

The present study evaluated the ability of KlamExtra®, an Aphanizomenon flos aquae (AFA) extract, to counteract metabolic dysfunctions due to a high fat diet (HFD) or to accelerate their reversion induced by switching an HFD to a normocaloric diet in mice with diet-induced obesity. A group of HFD mice was fed with an HFD supplemented with AFA (HFD-AFA) and another one was fed with regular chow (standard diet-STD) alone or supplemented with AFA (STD-AFA). AFA was able to significantly reduce body weight, hypertriglyceridemia, liver fat accumulation and adipocyte size in HFD mice. AFA also reduced hyperglycaemia, insulinaemia, HOMA-IR and ameliorated the glucose tolerance and the insulin response of obese mice. Furthermore, in obese mice AFA normalised the gene and the protein expression of factors involved in lipid metabolism (FAS, PPAR-γ, SREBP-1c and FAT-P mRNA), inflammation (TNF-α and IL-6 mRNA, NFkB and IL-10 proteins) and oxidative stress (ROS levels and SOD activity). Interestingly, AFA accelerated the STD-induced reversion of glucose dysmetabolism, hepatic and VAT inflammation and oxidative stress. In conclusion, AFA supplementation prevents HFD-induced dysmetabolism and accelerates the STD-dependent recovery of glucose dysmetabolism by positively modulating oxidative stress, inflammation and the expression of the genes linked to lipid metabolism.

Adolescent food insecurity in female rodents and susceptibility to diet-induced obesity

Food insecurity is defined as having limited or uncertain access to nutritious foods, and adolescent food insecurity is associated with obesity and disordered eating behaviors in humans. We developed a rodent model of adolescent food insecurity to determine whether adolescent food insecurity per se promotes increased susceptibility to diet-induced obesity and altered eating behaviors during adulthood. Female juvenile Wistar rats were singly housed and assigned to three experimental diets: food-secure with standard chow (CHOW), food-secure with a high-fat/sugar Western diet (WD), and food-insecure with WD (WD-FI). Food-secure rats (CHOW and WD) received meals at fixed feeding times (9:00, 13:00, and 16:00). WD-FI rats received meals at unpredictable intervals of the above-mentioned feeding times but had isocaloric amounts of food to WD. We investigated the impact of adolescent food insecurity on motivation for sucrose (Progressive Ratio), approach-avoidance behavior for palatable high-fat food (Approach-Avoidance task), and susceptibility to weight gain and hyperphagia when given an obesogenic choice diet. Secondary outcomes were the effects of food insecurity during development on anxiety-like behaviors (Open Field and Elevated Plus Maze) and learning and memory function (Novel Location Recognition task). Rodents with adolescent food insecurity showed a greater trend of weight gain and significantly increased fat mass and liver fat accumulation on an obesogenic diet in adulthood, despite no increases in motivation for sucrose or high-fat food. These data suggest that adolescent unpredictable food access increases susceptibility to diet-induced fat gain without impacting food motivation or food intake in female rodents. These findings are among a small group of recent studies modeling food insecurity in rodents and suggest that adolescent food insecurity in females may have long-term implications for metabolic physiology later in life.

Effects of pomelo sponge fermented by Monascus ruber on cholesterol metabolism and intestinal microbiota in high-fat diet mice

The purpose of this study is to produce Monascus ruber fermented pomelo sponge products (MFPS) utilizing low-cost pomelo sponge as a solid-state fermentation substrate, and to investigate the effects of MFPS on cholesterol metabolism and gut microbiota in mice. The study of oral MFPS treatment in high-fat diet mice uncovered that a high dosage of MFPS effectively inhibited the increase of body weight, reduced the accumulation of liver and epididymal fat and improved blood cholesterol metabolism in mice. Interestingly, MFPS consumption enhanced the liver's antioxidant capacity, cleared free radicals. Furthermore, HE staining demonstrated that MFPS effectively repaired liver damage. UPLC-QTOF/MS analysis of liver metabolomics revealed that MFPS intervention exerts a substantial regulatory impact on metabolic pathways encompassing alanine, aspartate and glutamate metabolism, biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis, tryptophan metabolism, glycerophospholipid metabolism, fatty acid degradation, folate biosynthesis, etc. High-throughput sequencing of 16S rRNA unveiled that MFPS mitigated the intestinal microbiota imbalance triggered by a high-fat diet, increasing the abundance of probiotics in the intestine, including Lactobacillus and Bifidobacterium. Therefore, these findings demonstrate that MFPS can improve abnormal cholesterol metabolism and balance intestinal flora, offering valuable insights for developing natural and effective cholesterol-lowering products.

Disentangling the impact of gluteofemoral versus visceral fat accumulation on cardiometabolic health using sex-stratified Mendelian randomization

Background and aimsIndividuals with a higher abdominal adipose tissue accumulation are at higher risk of developing cardiometabolic diseases. For a given body mass index (BMI), women typically present lower abdominal adipose tissue accumulation compared to men. Whether abdominal adiposity is a causal driver of cardiometabolic risk, or a mere marker of ectopic fat deposition is debated. MethodsWe investigated the sex-specific and sex-combined impact of height and BMI-adjusted gluteofemoral adipose tissue (GFATadj) adjusted abdominal subcutaneous adipose tissue (ASATadj) and adjusted visceral adipose tissue (VATadj) on cardiometabolic traits and diseases using Mendelian randomization. ResultsLeveraging genome-wide summary statistics on GFATadj, ASATadj and VATadj from 39,076 UK Biobank participants with full-body magnetic resonance imaging available, we found that GFATadj is associated with a more favourable cardiometabolic risk profile including lower low density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, fasting insulin, liver enzyme levels and blood pressure as well as higher high density lipoprotein (HDL) cholesterol levels. GFATadj also is negatively associated with ischemic stroke, coronary artery disease, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). ASATadj is not associated with cardiometabolic traits and diseases, whereas VATadj is associated with liver fat accumulation but not with NAFLD or other cardiometabolic traits or diseases. Although the absolute effect sizes of GFATadj on LDL cholesterol were more pronounced in women compared to men, most associations did not differ by sex. ConclusionsThe inability of subcutaneous fat depots to efficiently store energy substrates could be the causal factor underlying the association of visceral lipid deposition with cardiometabolic health.

Association between nonalcoholic fatty liver disease and type 2 diabetes: A bidirectional two-sample mendelian randomization study

ObjectiveThe aim of this study was to explore the mutually causal relationship between NAFLD and type 2 diabetes. MethodsBased on the data obtained from GWAS, this study employed bidirectional two-sample MR analysis to investigate the causal relationship between NAFLD and type 2 diabetes, and also examined the causal relationship between liver fat accumulation and type 2 diabetes as well as the relationship between NAFLD and FPG, IR. ResultsIn MR analysis of NAFLD and type 2 diabetes, when NAFLD as an exposure and type 2 diabetes as a result, the OR (95 % CI) was 1.10890 (1.00135–1.22801); in the reverse analysis, the OR value was not statistically significant. In MR analysis of NAFLD, FPG and IR, there was no statistical significance in both directions. In MR analysis of liver fat accumulation and type 2 diabetes, when liver fat as an exposure and type 2 diabetes as a result, the OR (95 % CI) was 1.17516 (1.02054–1.35321); in the reverse analysis, the OR value (95 % CI) was 1.06283 (1.02879–1.09799). ConclusionThere is a unidirectional causal relationship between NAFLD and type 2 diabetes. Furthermore, a bidirectional causal relationship exists between liver fat accumulation and type 2 diabetes.

HuangQi ChiFeng decoction maintains gut microbiota and bile acid homeostasis through FXR signaling to improve atherosclerosis

Huangqi Chifeng Decoction (HQCFT), a traditional Chinese medicine preparation, has long been used to treat cardiovascular and cerebrovascular diseases. However, the mechanism of the beneficial effect of HQCFT on atherosclerosis remains to be explored. In this work, to investigate the effects of HQCFT on bile acid (BA) metabolism and the gut microbiome in atherosclerosis, ApoE−/− mice were fed a with high-fat diet for 16 weeks to establish the AS model. HQCFT(1.95 g kg−1 and 3.9 g kg−1 per day) was administered intragastrically for 8 weeks to investigate the regulatory effects of HQCFT on gut microbiota and bile acid metabolism and to inhibit the occurrence and development of AS induced by a high-fat diet. Histopathology, liver function and blood lipids were used to assess whether HQCFT can reduce plaque area, regulate lipid levels and alleviate liver steatosis in AS mice. In addition, 16S rDNA sequencing was used to screen the gut microbiota structure, and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS) was used to determine the bile acid profile. The mRNA and protein expression levels of bile acid metabolism were detected by RT‒PCR and WB to find the potential correlation. Results: HQCFT can regulate gut microbiota disorders, which was achieved by increasing gut microbiota diversity and altering Proteobacteria, Desulfobacterota, Deferribacteres, Rodentibacter, Parasutterella, and Mucispirillum interference abundance to improve AS-induced gut microbiota. HQCFT can also adjust the content of bile acids (TCA, LCA, DCA, TDCA, TLCA, UDCA, etc.), regulate bile acid metabolism, relieve liver fat accumulation, and inhibit the process of AS. In addition, HQCFT can restore the abnormal metabolism of bile acid caused by AS by regulating the expression of farnesoid X receptor (FXR), liver X receptor α (LXRα), ABCA1, ABCG1 and CYP7A1. Conclusion: HQCFT may play a part in the prevention of atherosclerosis by inhibiting the FXR/LXRα axis, increasing the expression of CYP7A1 in the liver, and regulating the interaction between the gut microbiota and bile acid metabolism.

Plantain flour – A beneficial material for the organ and transcriptional profile of kidney of diabetic rats

This study investigated the ameliorative effects of plantain flour on the organs of diabetic rats, and explored the mechanism from the perspective of kidney transcription. Diabetes was induced in rats by streptozotocin (STZ) and a high-sugar and high-fat diet. The alleviation effects and molecular mechanism of diabetes by plantain flour at different doses (1 g/kg·Bw, 2 g/kg·Bw, and 4 g /kg·Bw) were evaluated based on the analysis of biochemical indicators, histological observations, homeostasis model, and kidney transcriptome. The findings demonstrated that the intervention of plantain flour can reduce the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and urea (UREA). The pathological study revealed that plantain flour can alleviate the pathological symptoms of fat accumulation in liver and kidney tissue. According to the homeostasis model, plantain flour was able to reduce insulin resistance in diabetic rats. Transcriptome analysis showed that plantain flour improved dyslipidemia by up-regulating Acsl1, down-regulating Fabp4 and Plin1, and reduced kidney injury by up-regulating Slco1a6, Hsd17b2, Cyp2c24, and Cyp2c11 genes. These results suggested that plantain flour could improve the organ damage caused by diabetes and has the potential to be developed into healthy food.

Modulatory effects of policosanol from insect wax on lipid metabolism in high-fat diet-fed rats

Insect wax is a traditional Chinese medicine, which can be converted into policosanol through a reduction reaction. The efficacy of policosanol from insect wax (PIW) depends on its purity and composition ratio. Plant-derived policosanol has a hypolipidemic effect, however, the effects of PIW on serum lipid levels have not yet been clarified. In this study, we investigated the effects of orally administered PIW on lipid metabolism in rats fed a high-fat diet. We found that PIW administration reduced the serum lipid levels of rats fed a high-fat diet, ameliorated body weight gain, and alleviated liver fat accumulation. This effect could be associated with the upregulation of fatty acid breakdown- and lipid metabolism–related genes, Pparα and Pparβ/δ, downregulation of fatty acid absorption and storage-related genes, Srebp1c, Il6, and Tnfα, and an antioxidant effect. These findings suggest the potential utility of PIW for developing functional foods with lipid-lowering capabilities.

Long term survival and abnormal liver fat accumulation in mice with specific thymidine kinase 2 deficiency in liver tissue.

Deficiency in thymidine kinase 2 (TK2) causes mitochondrial DNA depletion. Liver mitochondria are severely affected in Tk2 complete knockout models and have been suggested to play a role in the pathogenesis of the Tk2 knockout phenotype, characterized by loss of hypodermal fat tissue, growth retardation and reduced life span. Here we report a liver specific Tk2 knockout (KO) model to further study mechanisms contributing to the phenotypic changes associated with Tk2 deficiency. Interestingly, the liver specific Tk2 KO mice had a normal life span despite a much lower mtDNA level in liver tissue. Mitochondrial DNA encoded peptide COXI did not differ between the Tk2 KO and control mice. However, the relative liver weight was significantly increased in the male Tk2 KO mouse model. Histology analysis indicated an increased lipid accumulation. We conclude that other enzyme activities can partly compensate Tk2 deficiency to maintain mtDNA at a low but stable level throughout the life span of the liver specific Tk2 KO mice. The lower level of mtDNA was sufficient for survival but led to an abnormal lipid accumulation in liver tissue.

Plasma IGFBP-2 levels reveal heterogeneity in hepatic fat content in adults with excess visceral adiposity.

Obesity is frequently accompanied by a fatty liver. However, some individuals with high abdominal fat levels nevertheless have low levels of liver fat. Reasons for such discordant phenotypes are unclear. In this paper, we report that among asymptomatic individuals with high levels of visceral fat, low concentrations of IGFBP-2 in the circulation were associated with significantly higher hepatic fat content compared to those with high IGFBP-2 levels. We conclude that quantification of plasma IGFBP-2 concentrations may be useful to identify the early risk for liver fat accumulation in apparently healthy individuals without cardiovascular symptoms. Although excess visceral adiposity (VAT) is generally associated with increased liver fat (LF), recent evidence has revealed heterogeneity in LF content among adults with visceral obesity, potentially contributing to specific differences in cardiometabolic outcomes. Reasons for such discordant VAT-LF phenotypes are largely unknown. The present study aimed at assessing whether circulating levels of insulin growth-factor binding protein-2 (IGFBP-2) could be a useful biomarker in the identification of heterogenous and discordant VAT-LF phenotypes. A sample of 308 middle-aged Caucasian apparently healthy men and women without cardiovascular symptoms were studied for the present cross-sectional analyses. Fasting plasma glucose and lipid levels were assessed and an oral glucose tolerance test was performed. Hepatic fat fraction (HFF) was measured using magnetic resonance spectroscopy whereas VAT was assessed by magnetic resonance imaging. Plasma IGFBP-2 levels were quantified by ELISA. Participants were then classified on the basis of median VAT (81 mL) and IGFBP-2 levels (233 ng/mL). Individuals with high levels of VAT were characterized by higher waist circumference, lower insulin sensitivity, as well as by higher plasma triglyceride and lower HDL-cholesterol levels. Plasma IGFBP-2 levels were inversely correlated with HFF (r = -0.39, p < 0.0001). Among men and women with high levels of VAT, those with low levels of IGFBP-2 had significantly higher HFF (7.5 ± 0.7%), compared to participants with high IGFBP-2 concentrations (3.2 ± 0.5%, p < 0.0001). In the presence of excess VAT, high IGFBP-2 concentrations are associated with low levels of LF. Although additional studies will be necessary to establish causality and further clarify the clinical implications of these observations, these findings are concordant with a novel function of IGFBP-2 in modulating susceptibility to non-alcoholic fatty liver disease (NAFLD) in the presence of visceral obesity.

Hepatobiliary and pancreatic: Multi-donor fecal microbiota transplantation attenuated high-fat diet-induced hepatic steatosis in mice by remodeling the gut microbiota.

Fecal microbiota transplantation (FMT) can improve the symptoms of nonalcoholic fatty liver disease (NAFLD) by restoring the gut microbiota. This study was aimed to evaluate the therapeutic effects of single-donor (SD) or multi-donor (MD) FMT in a mouse model of hepatic steatosis and explore the underlying mechanisms. Fecal samples were collected from NAFLD patients and healthy controls with similar baseline characteristics, with gut microbiota analyzed. Mice were fed either a normal-chow diet (NCD) or a high-fat diet (HFD) for 3weeks and then administered fecal microbiota collected from healthy SDs or MDs for 12weeks. Fecal samples from NAFLD patients showed significantly lower microbial diversity than those from healthy controls. MD-FMT reduced liver fat accumulation and body weight and significantly improved serum and liver biochemical indices in HFD-fed mice. Compared to untreated HFD-fed mice, MD-FMT significantly decreased the relative expression of IL-1β, IL-6, TNF-α, IFN-γ, and IL-1β mRNAs in the liver. The relative protein level of intestinal barrier components, including claudin-1, occludin, and E-cadherin, as well as serum lipopolysaccharide (LPS) level in mice, were found to be improved following MD-FMT intervention. Furthermore, FMT reversed HFD-induced gut dysbiosis and increased the abundance of beneficial bacteria such as Blautia and Akkermansia. NAFLD patients and healthy controls showed distinct gut microbiota. Likewise, HFD altered gut microbiota in mice compared to NCD-fed controls. MD-FMT restored gut dysbiosis in HFD-fed mice and attenuated liver steatosis, and should be considered as an effective treatment option for NAFLD.

Water Extract of Angelica dahurica Inhibits Osteoclast Differentiation and Bone Loss.

Angelica dahurica radix has a long history of traditional use in China and Korea for treating headaches, cold-damp pain and skin diseases. Despite various pharmacological studies on A. dahurica, its impact on bones remains unclear. Hence, this study investigated the inhibitory effect of A. dahurica's radix water extract (WEAD) on osteoclast differentiation. In vitro experiments showed that WEAD effectively suppresses osteoclast differentiation. Treatment of an osteoclast precursor with WEAD significantly suppressed the expression of nuclear factor of activated T-cells 1 (NFATc1), essential transcription factor for osteoclastogenesis, while increasing the expression of negative regulators, interferon regulatory factor 8 (Irf8) and v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MafB). Consistent with the in vitro findings, the oral administration of WEAD (100 and 300 mg/kg/day) to mice subjected to surgical ovariectomy for a duration of six weeks alleviated bone loss, while also mitigating weight gain and liver fat accumulation. In addition, we also identified phytochemicals present in WEAD, known to regulate osteoclastogenesis and/or bone loss. These results suggest the potential use of WEAD for treating various bone disorders caused by excessive bone resorption.

Altered Lipid Moieties and Carbonyls in a Wistar Rat Dietary Model of Subclinical Fatty Liver: Potential Sex-Specific Biomarkers of Early Fatty Liver Disease?

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.

Fucogalactan Sulfate (FS) from Laminaria japonica Regulates Lipid Metabolism in Diet-Induced Humanized Dyslipidemia Mice via an Intestinal FXR-FGF19-CYP7A1/CYP8B1 Pathway.

Our previous study found that fucogalactan sulfate (FS) from Laminaria japonica exhibited significant hypolipidemic effects. To further elucidate the mechanism, we first constructed a dyslipidemia mouse model with humanized gut microbiota and proved the main differential metabolic pathway involved bile acid metabolism. Then, we evaluated the beneficial effects of FS on dyslipidemia in this model mice, which revealed that oral FS administration reduced serum cholesterol levels and mitigated liver fat accumulation. Gut microbiota and microbiome analysis showed FS increased the abundance of Ruminococcaceae_NK4A214_group, GCA-900066755, and Eubacterium, which were positively associated with the fecal DCA, β-MCA, and HDCA. Further investigation demonstrated that FS inhibited the hepatic farnesoid X receptor (FXR), while activating the intestinal FXR-FGF19 pathway, leading to suppression of CYP7A1 and CYP8B1, as well as potentially reduced bile acid synthesis and lipid absorption. Overall, FS regulated lipid metabolism in diet-induced humanized dyslipidemia mice via the bile acid-mediated intestinal FXR-FGF19-CYP7A1/CYP8B1 pathway.

Impact of elobixibat on liver tumors, microbiome, and bile acid levels in a mouse model of nonalcoholic steatohepatitis.

Elevated bile acid levels have been associated with liver tumors in fatty liver. Ileal bile acid transporter inhibitors may inhibit bile acid absorption in the distal ileum and increase bile acid levels in the colon, potentially decreasing the serum and hepatic bile acid levels. This study aimed to investigate the impact of these factors on liver tumor. C57BL/6J mice received a one-time intraperitoneal injection of 25-mg/kg diethylnitrosamine. They were fed a choline-deficient high-fat diet for 20weeks starting from 8weeks of age, with or without elobixibat (EA Pharma, Tokyo, Japan). Both groups showed liver fat accumulation and fibrosis, with no significant differences between the two groups. However, mice with elobixibat showed fewer liver tumors. The total serum bile acid levels, including free, tauro-conjugated, glyco-conjugated, and tauro-α/β-muricholic acids in the liver, were noticeably reduced following elobixibat treatment. The proportion of gram-positive bacteria in feces was significantly lower in the group treated with elobixibat (5.4%) than in the group without elobixibat (33.7%). Elobixibat suppressed tumor growth by inhibiting bile acid reabsorption, and decreasing total bile acid and primary bile acid levels in the serum and liver. Additionally, the presence of bile acids in the colon may have led to a significant reduction in the proportion of gram-positive bacteria, potentially resulting in decreased secondary bile acid synthesis.

Dietary factors in nonalcoholic fatty liver disease: impacts on human and animal health - a review

Abstract Non-alcoholic fatty liver disease (NAFLD) is defined as a clinical syndrome characterized by excessive fat accumulation in liver, predominantly influenced by dietary choices. This study provides an extensive quantitative literature analysis on dietary influences on NAFLD. Bibliometric data were collected through the search string TOPIC = (“NAFLD*” OR “nonalcoholic fatty liver*” OR “non-alcoholic fatty liver*”) AND TOPIC = (“diet*” OR “nutrition*” OR “food*” OR “feed*”), which yielded 12,445 publications indexed within the Web of Science Core Collection. Utilizing VOSviewer software, term maps were generated to visually illustrate recurring phrases alongside citation data. The literature, which has seen exponential growth since the 2010s, predominantly consists of original articles, with a ratio of 4.7:1 compared to reviews. Notably, the significant contributors to this field were China and the United States. The majority of publications were found journals specialized in Gastroenterology &amp; Hepatology, Nutrition &amp; Dietetics, Biochemistry &amp; Molecular Biology, Endocrinology &amp; Metabolism, and Pharmacology &amp; Pharmacy. Key dietary compounds/compounds classes such as resveratrol, polyphenols, curcumin, berberine, quercetin, flavonoids, omega-3 fatty acids, docosahexaenoic acid (DHA), genistein, and palmitic acid were frequently mentioned and cited. Many of them were demonstrated to have some potential benefits on NAFLD, both in human and animal studies.

Amelioration of ethanol-induced oxidative stress and alcoholic liver disease by invivo RNAi targeting Cyp2e1.

Alcoholic liver disease (ALD) results from continuous and heavy alcohol consumption. The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention, which is a long process with poor efficacy and low patient compliance. Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD, but CYP2E1 knockdown in humans was impractical, and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown. In this study, we developed a RNAi therapeutics delivered by lipid nanoparticle, and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks. This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers, and contributed to improved ALD symptoms in mice. The liver fat accumulation, hepatocyte inflammation, and fibrosis were reduced in ALD models. Therefore, this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.

Prenatal High-Fat Diet Combined with Microplastic Exposure Induces Liver Injury via Oxidative Stress in Male Pups.

Prenatal high-fat diet (HFD) or exposure to microplastics can affect the accumulation of liver fat in offspring. We sought to determine the effects of maternal HFD intake and microplastic exposure on fatty liver injury through oxidative stress in pups. Pregnant female Sprague-Dawley rats were randomly divided into maternal HFD (experimental group) or normal control diet (NCD; control group) groups with or without microplastic exposure. As a result, the following groups were established: HFD-L (HFD + microplastics, 5 µm, 100 μg/L), HFD-H (HFD + microplastics, 5 µm, 1000 μg/L), NCD-L (NCD + microplastics, 5 µm, 100 μg/L), and NCD-H (NCD + microplastics, 5 µm, 1000 μg/L). The pups were sacrificed on postnatal day 7 (PD7). Liver histology revealed increased hepatic lipid accumulation in pups in the HFD-L and HFD-H groups compared to those in the HFD, NCD-L, NCD-H, and NCD groups on PD7. Similarly, liver TUNEL staining and cellular apoptosis were found to increase in pups in the HFD-L and HFD-H groups compared to those in the HFD, NCD-L, NCD-H, and NCD groups. The expression levels of malondialdehyde, a lipid peroxidation marker, were high in the HFD, HFD-L, and HFD-H groups; however, the highest expression was observed in the HFD-H group (p < 0.05). The levels of glutathione peroxidase, an antioxidant enzyme, decreased in the HFD, HFD-L, and HFD-H groups (p < 0.05). Overall, oxidative stress with cellular apoptosis plays a vital role in liver injury in offspring after maternal intake of HFD and exposure to microplastic; such findings may shed light on future therapeutic strategies.

Aflatoxin B1-induced early developmental hepatotoxicity in larvae zebrafish

Aflatoxin B1 (AFB1) is a ubiquitous mycotoxin that causes oxidative damage in various organs. At present, the research studies on AFB1 are primarily focused on its effects on the terrestrial environment and animals. However, its toxicity mechanism in aquatic environments and aquatic animals has not been largely explored. Thus, in this study, zebrafish was used as a model to study the toxicity mechanism of AFB1 on the liver of developing larvae. The results showed that AFB1 exposure inhibited liver development and promoted fat accumulation in the liver. Transcriptome sequencing analysis showed that AFB1 affected liver redox metabolism and oxidoreductase activity. KEGG analysis showed that AFB1 inhibited the expression of gsto1, gpx4a, mgst3a, and idh1 in the glutathione metabolizing enzyme gene pathway, resulting in hepatic oxidative stress. At the same time, AFB1 also inhibited the expression of acox1, acsl1b, pparα, fabp2, and cpt1 genes in peroxidase and PPAR metabolic pathways, inducing hepatic steatosis and lipid droplet accumulation. Antioxidant N-Acetyl-l-cysteine (NAC) preconditioning up-regulated gsto1, gpx4a and idh1 genes, and improved the AFB1-induced lipid droplet accumulation in the liver. In summary, AFB1 induced hepatic oxidative stress and steatosis, resulting in abnormal liver fat metabolism and accumulation of cellular lipid droplets. NAC could be used as a potential preventative drug to improve AFB1-induced fat accumulation.