Fatty Liver Tissue Research Articles

Characteristics of the microstructure and the key components of white kidney bean sourdough bread induced by mixed-strain fermentation and its influence on gut microbiota.

In this study, the effect of mixed-strain fermentation using Kluyveromyces marxianus with either Lactobacillus plantarum or Pediococcus pentosaceus on the physiochemical and nutritional properties of white kidney bean flour sourdough was investigated. The results indicated that mixed-strain fermentation reduced the anti-nutritional factors produced from the white kidney bean flour, especially in the sourdough fermented by L. plantarum and K. marxianus (WKS-LK) compared to that by P. pentosaceus and K. marxianus (WKS-JK). Meanwhile, the content of lactic acid and acetic acid and the proportion of peptides with molecular weights ranging from <500 to 5000 Da were increased in the sourdoughs (WKS-LK > WKS-JK). Compared to the control (WK), microstructural characteristics of the dough seemed to be improved in WKS-LK followed by WKS-JK in terms of their corresponding gluten network consistency. Moreover, mixed fermentation led to a reduced starch digestibility accompanied by a higher content of resistant starch and slowly digestible starch. In contrast, protein digestibility was enhanced in WKS-LK and WKS-JK sourdough breads. More importantly, the changes in gut microbiota composition, short-chain fatty acid (SCFA) production, systemic inflammation, glucose tolerance and liver tissue histopathology following 21-day consumption of the sourdough bread were also evaluated via an animal model. The intake of sourdough breads reduced the abundance of the pathogenic microbiota Escherichia shigella. In contrast, the corresponding abundance of Rikenellaceae, Akkermansiaceae, Erysipelotrichaceae, Prevotellaceae and Eubacterium coprostanoligenes was increased, followed by enhanced SCFA generation, with the highest in WKS-LK and then WKS-JK. Meanwhile, a reduced level of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α in the serum and improved glucose tolerance and liver tissue histopathology following the bread consumption were also achieved in the order of WKS-LK, then WKS-JK mice compared to WK.

Decreased autophagosome biogenesis, reduced NRF2, and enhanced ferroptotic cell death are underlying molecular mechanisms of non-alcoholic fatty liver disease

Background and aimsCaloric excess and sedentary lifestyles have led to an epidemic of obesity, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD). The objective of this study was to investigate the mechanisms underlying high fat diet (HFD)-induced NAFLD, and to explore NRF2 activation as a strategy to alleviate NAFLD. Approach and resultsHerein, we demonstrated that high fat diet (HFD) induced lipid peroxidation and ferroptosis, both of which could be alleviated by NRF2 upregulation. Mechanistically, HFD suppressed autophagosome biogenesis through AMPK- and AKT-mediated mTOR activation and decreased ATG7, resulting in KEAP1 stabilization and decreased NRF2 levels in mouse liver. Furthermore, ATG7 is required for HFD-induced NRF2 downregulation, as ATG7 deletion in Cre-inducible ATG7 knockout mice decreased NRF2 levels and enhanced ferroptosis, which was not further exacerbated by HFD. This finding was recapitulated in mouse hepatocytes, which showed a similar phenotype upon treatment with saturated fatty acids (SFAs) but not monounsaturated fatty acids (MUFAs). Finally, NRF2 activation blocked fatty acid (FA)-mediated NRF2 downregulation, lipid peroxidation, and ferroptosis. Importantly, the HFD-induced alterations were also observed in human fatty liver tissue samples. ConclusionsHFD-mediated autophagy inhibition, NRF2 suppression, and ferroptosis promotion are important molecular mechanisms of obesity-driven metabolic diseases. NRF2 activation counteracts HFD-mediated NRF2 suppression and ferroptotic cell death. In addition, SFA vs. MUFA regulation of NRF2 may underlie their harmful vs. beneficial effects. Our study reveals NRF2 as a key player in the development and progression of fatty liver disease and that NRF2 activation could serve as a potential therapeutic strategy.

MiR-9 and miR-181a Target Gab2 to Inhibit the Proliferation and Migration of Hepatocellular Carcinoma HepG2 Cells.

The incidence of liver cancer ranks seventh globally, with nearly half of all cases occurring in East Asia, but currently, there are very few drugs to treat it. Our previous studies demonstrated that the signal integration protein Gab2 is a potential drug target for the prevention and therapy of liver cancer. Here, we screened for and identified two miRNAs that target Gab2 to suppress the proliferation and migration of hepatocellular carcinoma (HCC) cells. First, we predicted Gab2-targeting miRNAs through biological websites, and we selected nine miRNAs that were reported in the literature as being abnormally expressed in liver cancer and fatty liver tissue. Then, we measured the expression of these miRNAs in the hepatic epithelial cell line HL-7702 and the HCC cell line HepG2. The expression levels of miR-9, miR-181a, miR-181c, miR-34a, and miR-134 were high in HL-7702 cells but low in HepG2 cells, and their expression patterns were the opposite of Gab2 in these cells. Furthermore, we transfected miR-9, miR-34a, miR-181a, and miR-181c mimics into HepG2 cells and found that only miR-9 and miR-181a reduced the level of Gab2 proteins. miR-9 also reduced the Gab2 mRNA level, but miR-181a did not affect the Gab2 mRNA levels. Using a miRNA-Gab2 3'UTR binding reporter, we confirmed that miR-9 and miR-181a bind to the Gab2 3'UTR region. Finally, we introduced miR-9 and miR-181a mimics into HepG2 cells and found that cell proliferation and migration were significantly inhibited. In conclusion, we identified two novel miRNAs targeting Gab2 and provided potential drug targets for the prevention and treatment of liver cancer.

MiR-375 upregulates lipid metabolism and inhibits cell proliferation involved in chicken fatty liver formation and inheritance via targeting recombination signal binding protein for immunoglobulin kappa J region (RBPJ)

Poultry is susceptible to fatty liver which lead to decrease egg production and increase mortality. But the potential molecular mechanisms remain largely unclear. In the current study, in combination with transcriptome sequencing and miRNA sequencing data analysis from F1 generation of the normal liver and fatty liver tissues, the differentially expressed miR-375 and its target gene RBPJ were screened and verified. The expression levels of miR-375 and RBPJ gene in the liver between control and fatty liver groups of F0-F3 generation for Jingxing-Huang (JXH) chicken are different significantly (P < 0.05 or P < 0.01). And downregulated RBPJ expression can promote TG content and lipid droplets in primary hepatocytes cultured in vitro (P < 0.01). Cell proliferation-related genes, including PMP22, IGF-1, IGF-2, and IGFBP-5, increased or decreased significantly after overexpression or knock-down RBPJ (P < 0.05 or P < 0.01), respectively. This study uniquely revealed that miR-375 induced lipid synthesis and inhibited cell proliferation may partly due to regulation of RBPJ expression, thereby involving in fatty liver formation and inheritance in chicken. The results could be useful in identifying candidate genes and revealing the pathogenesis of fatty liver that may be used for disease-resistance selective breeding in chicken.

Fatty Liver/Adipose Tissue Dual-Targeting Nanoparticles with Heme Oxygenase-1 Inducer for Amelioration of Obesity, Obesity-Induced Type 2 Diabetes, and Steatohepatitis.

Persistent uptake of high-calorie diets induces the storage of excessive lipid in visceral adipose tissue. Lipids secreted from obese adipose tissue are accumulated in peripheral tissues such as the liver, pancreas, and muscle, and impair insulin sensitivity causing type 2 diabetes mellitus (T2DM). Furthermore, the accumulation of inflammatory cytokines and lipids in the liver induces apoptosis and fibrogenesis, and ultimately causes nonalcoholic steatohepatitis (NASH). To modulate obese tissue environments, it is challenged to selectively deliver inducers of heme oxygenase-1 (HO-1) to adipose tissue with the aid of a prohibitin targeting drug delivery system. Prohibitin binding peptide (PBP), an oligopeptide targeting prohibitin rich in adipose tissue, is conjugated on the surface of Hemin- or CoPP-loaded poly(lactide-co-glycolide) nanoparticles (PBP-NPs). PBP-NPs efficiently differentiate lipid storing white adipocytes into energy-generating brown adipocytes in T2DM and NASH models. In addition, PBP-NPs are found to target prohibitin overexpressed fatty liver in the NASH model and inhibit hepatic uptake of circulating lipids. Furthermore, PBP-NPs switch phenotypes of inflammatory macrophages in damaged organs and lower inflammation. Taken together, dual-targeted induction of HO-1 in fatty adipose and liver tissues is proven to be a promising therapeutic strategy to ameliorate obesity, insulin resistance, and steatohepatitis by lowering lipids and cytokines.

An improved method for isolation and flow cytometric characterization of intrahepatic leukocytes from fatty and fibrotic liver tissues.

Flow cytometry is an imperative tool to characterize alterations in a wide range of immune cell populations during inflammatory conditions and disease states that affect the liver such as the obesity-induced non-alcoholic fatty liver disease and liver fibrosis. Identification and quantification of immune cell subsets from the liver is critically dependent on efficient isolation of intrahepatic leukocytes. The isolation of leukocytes from fatty and fibrotic livers and processing the cells for flow cytometry can be challenging with respect to cell yields, purity and most importantly, the level of autofluorescence resulting from fat deposition. Here, we describe an efficient method for isolating intrahepatic leukocytes from mice fed with high fat diet and propose a strategy to alleviate autofluorescence during phenotyping by multicolor flowcytometry. We also describe a gating strategy for robust identification of granulocytes, pro-inflammatory, anti-inflammatory and transitional state monocyte subsets, dendritic cells, B cell, T lymphocyte subpopulations and NK cell subsets. Overall, the procedures described here will allow simultaneous processing of several samples while ensuring reproducible cell isolation and efficient noise reduction required for reliable characterization of intrahepatic leukocytes from the fatty liver tissues.

Polarity-Sensitive Probe: Dual-Channel Visualization of the "Chameleon" Migration with the Assistance of Reactive Oxygen Species.

The real-time and differentiated visualization of the organelles is favorable for exploring the distribution and interaction. However, most visual probes emit monochromatic fluorescence and target a single organelle, which impedes the in-depth study of their interplay. To overcome this obstacle, we tactfully conceived a polarity-sensitive fluorescent DPDO-C that could accurately discriminate polarity changes in the cellular environment, exhibiting distinct fluorescence in lipid droplets (LDs) and mitochondria. Remarkably, the probe DPDO-C could migrate from mitochondria to LDs with the assistance of reactive oxygen species, which was conducive to further monitoring of the number and size of LDs as well as the interactions between LDs and other organelles. Moreover, the nuanced difference between normal and fatty liver tissues was also distinguished by two-color fluorescence imaging, which could act as a promising candidate for the early diagnosis of fatty liver.

A mitochondria-targeted and viscosity-sensitive near-infrared fluorescent probe for visualization of fatty liver, inflammation and photodynamic cancer therapy

Elucidating the intrinsic relationship between disease and mitochondrial viscosity is great significance for understanding the diagnosis and treatment of fatty liver, inflammation and cancer. However, the development of a single mitochondrial viscosity fluorescent probe capable of visualizing multiple disease models and achieving photodynamic cancer therapy function is severely deficient and remains a great challenge. Herein we intelligently designed a mitochondria-targeted and viscosity-sensitive near-infrared (NIR) fluorescent probe POTA-OH, containing a p-hydroxydiphenylamino substituted oxanthracene moiety as the strong electron donor (D), a pyridinium cationic unit as the electron acceptor (A) and the mitochondria-targeted group. With increasing the viscosity level, POTA-OH displayed a significant “turn-on” fluorescence behavior at 720 nm, and an excellent linear relationship with viscosity from 0.89 cP to 945 cP. Meanwhile, POTA-OH could achieve effective reactive oxygen species production upon a 635 nm red laser irradiation. Using POTA-OH, we have demonstrated the visualization of fatty liver tissues, inflammation living mice, tumor living mice and even clinic cancer patient tissues samples via mitochondrial viscosity imaging. Furthermore, we revealed that POTA-OH has the potential of simultaneous PDT treatment in vitro and immediate evaluation of its therapeutic effect. Importantly, high-efficient PDT of POTA-OH has also successfully achieved for in vivo PDT antitumor, making it a promising integrated reagent for cancer diagnosis, treatment and even evaluation of PDT efficacy.

MiR-103-3p promotes hepatic steatosis to aggravate nonalcoholic fatty liver disease by targeting of ACOX1

BackgroundNonalcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma, and alterations in miRNA expression are related to the development of NAFLD. However, the role of miRNAs in regulating the development of NAFLD is still poorly understood.MethodsWe used qRT-PCR to detect the level of miR-103-3p in both cell and mouse models of NAFLD. Biochemical assays, DCF-DA assays, Oil red O staining and HE staining were used to detect the role of miR-103-3p in NAFLD development. Target genes of miR-103-3p were predicted using the TargetScan database and verified by qRT-PCR, western blot and dual-luciferase assays.ResultsThe expression of miR-103-3p increased in both NAFLD model cells and liver tissues from the NAFLD mouse model. Inhibition of miR-103-3p significantly alleviated the accumulation of lipid droplets in free fatty acid-treated L02 cells and liver tissues from mice with NAFLD. Inhibition of miR-103-3p reduced the contents of H2O2, TG, ALT, and AST and ROS production while increasing the ATP content. Moreover, the miR-103-3p antagomir alleviated liver tissue lesions in mice with NAFLD. Further studies identified ACOX1, a key enzyme for the oxidation and decomposition of fatty acids, as a direct target of miR-103-3p.ConclusionsThese findings identified a negative regulatory mechanism between ACOX1 and miR-103-3p that promotes the pathogenesis of NAFLD and suggested that inhibition of miR-103-3p may be a potential treatment strategy for NAFLD.

Monkfish Peptides Mitigate High Fat Diet-Induced Hepatic Steatosis in Mice.

Non-alcoholic fatty liver disease (NAFLD) is a hepatic metabolic syndrome usually accompanied by fatty degeneration and functional impairment. The aim of the study was to determine whether monkfish peptides (LPs) could ameliorate high-fat diet (HFD)-induced NAFLD and its underlying mechanisms. NAFLD was induced in mice by giving them an HFD for eight weeks, after which LPs were administered in various dosages. In comparison to the HFD control group: body weight in the LP-treated groups decreased by 23–28%; triacylglycerol levels in the blood decreased by 16–35%; and low-density lipoproteins levels in the blood decreased by 23–51%. Additionally, we found that LPs elevated the activity of hepatic antioxidant enzymes and reduced the inflammatory reactions within fatty liver tissue. Investigating the effect on metabolic pathways, we found that in LP-treated mice: the levels of phospho-AMP-activated protein kinase (p-AMPK), and phospho-acetyl CoA carboxylase (p-ACC) in the AMP-activated protein kinase (AMPK) pathway were up-regulated and the levels of downstream sterol regulatory element-binding transcription factor 1 (SREBP-1) were down-regulated; lipid oxidation increased and free fatty acid (FFA) accumulation decreased (revealed by the increased carnitine palmitoyltransferase-1 (CPT-1) and the decreased fatty acid synthase (FASN) expression, respectively); the nuclear factor erythroid-2-related factor 2 (Nrf2) antioxidant pathway was activated; and the levels of heme oxygenase-1 (HO-1) and nicotinamide quinone oxidoreductase 1 (NQO1) were increased. Overall, all these findings demonstrated that LPs can improve the antioxidant capacity of liver to alleviate NAFLD progression mainly through modulating the AMPK and Nrf2 pathways, and thus it could be considered as an effective candidate in the treatment of human NAFLD.

HPS protects the liver against steatosis, cell death, inflammation, and fibrosis in mice with steatohepatitis.

Hepassocin (HPS) is a hepatokine associated with metabolic regulation and development of non-alcoholic steatohepatitis (NASH). However, previous reports on HPS are controversial and its true function is not yet understood. Here, we demonstrated that hepatic HPS expression levels were upregulated in short-term feeding and downregulated in long-term feeding in high-fat diet (HFD)- and methionine- and choline-deficient (MCD) diet-fed mice, as well as in genetically obese (ob/ob) mice. HFD- and MCD-induced hepatic steatosis, inflammation, apoptosis, and fibrosis were more pronounced in HPS knockout mice than in the wild-type mice. Moreover, HPS depletion aggravated HFD-induced insulin resistance. By contrast, HPS administration improved MCD- or HFD-induced liver phenotypes and insulin resistance in HPS knockout and wild-type mice. Mechanistic studies revealed that MCD-induced hepatic oxidative stress was significantly increased by HPS deficiency and could be attenuated by HPS administration. Furthermore, palmitic acid-induced lipid accumulation and oxidative stress were exclusively enhanced in HPS knockout hepatocytes and diminished by HPS cotreatment. These data suggest that HPS ameliorates NASH in mice, at least in part, by inhibiting the oxidative stress. HPS expression levels are downregulated in human fatty liver tissues, suggesting that it may play an important protective role in NASH. Collectively, our findings provide clear genetic evidence that HPS has beneficial effects on the development of steatohepatitis in mice and suggest that upregulating HPS signaling may represent an effective treatment strategy for NASH.

A smart probe for simultaneous imaging of the lipid/water microenvironment in atherosclerosis and fatty liver.

A smart lipid droplet specific fluorescent probe (LDs-DM) with dual-emission in water (706 nm) and oil (535 nm) under single-excitation was prepared for revealing the ultra-structure of the aqueous and lipidic microenvironment in living cells, fatty liver tissues and atherosclerotic plaques without fluorescence emission crosstalk. This work is expected to provide inspiration for designing a novel probe with color switching ability.

Protective Effect of Polysaccharide from Gastrodia elata Blume on Nonalcoholic Fatty Liver Induced by High Fat Diet

Objective: To investigate the protective and delayed effects of Gastrodia elata polysaccharide on nonalcoholic fatty liver (NAFLD) and its molecular mechanism. Methods:60 ICR mice were randomly divided into normal group, model group and Gastrodia elata polysaccharide group (50, 100 and 200 mg/kg). Except the normal group, the other groups were given high-fat diet to induce NAFLD model. At the same time, the corresponding drugs were given once a day for 10 weeks. At 12 hours after the last administration, the body weight and organ index of mice were recorded, the pathological changes of liver tissue were evaluated by histopathology. At the same time, the activity of serum aspartate amino transferase (AST) and alanine amino transferase (ALT) were measured, and the related signal transduction pathways were examined including oxidative stress injury and lipid metabolism. Results:Compared with the model group, the activity of AST and ALT in serum were significantly decreased (P <0.05), and the pathological symptoms of fatty liver tissue was alleviated, and the level of genes expression related to lipid accumulation were regulated to improve lipid metabolism (P<0.05); In addition, Gastrodia elata polysaccharide also improved oxidative stress injury by upregulating Nrf2/GPX signaling pathway (P<0.05), inhibited the expression of NF-κB, TNF-α, IL-1β, iNOS and COX-2 proteins related to inflammatory response (P<0.05), and inhibited the expression of Bax and upregulated Bcl-2 proteins (P<0.05). Conclusion: Gastrodia elata Blume polysaccharide (GBP) can improve the liver function of NAFLD model mice, regulate the level of lipid metabolism and reduce the accumulation of fat, alleviate the oxidative stress injury of liver and inhibit inflammation to protect and delay NAFLD symptoms caused by high fat diet.

The Correlation between Extracellular Heat Shock Protein 70 and Lipid Metabolism in a Ruminant Model.

Metabolic stress in early lactation cows is characterized by lipolysis, ketogenesis, insulin resistance and inflammation because of negative energy balance and increased use of lipids for energy needs. In this study the relationship between lipid metabolite, lipid-based insulin resistance, and hepatocyte functionality indexes and tumor necrosis factor alpha (TNF-α) with extracellular heat shock protein 70 (eHsp70) was investigated. The experiment included 50 cows and all parameters were measured in blood serum. In cows with a more pronounced negative energy balance, the following was determined: a higher concentration of eHsp70, TNF-α, non-esterified fatty acid (NEFA), beta-hydroxybutyrate (BHB), NEFA to insulin and NEFA to cholesterol ratio and lower concentration of cholesterol, very low-density lipoproteins (VLDL), low density lipoproteins (LDL) and liver functionality index (LFI). The eHsp70 correlated negatively with the values of cholesterol, VLDL, LDL, and triglycerides, while correlated positively with the level of NEFA and BHB. A higher concentration of eHsp70 suggests the development of fatty liver (due to a higher NEFA to cholesterol ratio and lower LFI) and insulin resistance (due to a lower revised quantitative insulin sensitivity check index RQUICKI-BHB and higher NEFA to insulin ratio). The eHsp70 correlated positively with TNF-α. Both TNF-α and eHsp70 correlated similarly to lipid metabolites. In cows with high eHsp70 and TNF-α values we found higher concentrations of NEFA, BHB, NEFA to insulin and NEFA to cholesterol ratio and a lower concentration of triglycerides and VLDL cholesterol compared to cows that had only high TNF-α values. Based on the positive correlation between eHsp70 and TNF-α, their similar relations, and the additional effect of eHsp70 (high TNF-α + eHsp70 values) on lipid metabolites we conclude that eHsp70 has pro-inflammatory effects implicating lipolysis, fatty liver, and fat tissue insulin resistance.

Novel β-mannanase/GLP-1 fusion peptide high effectively ameliorates obesity in a mouse model by modifying balance of gut microbiota

We constructed a novel β-mannanase/GLP-1 fusion peptide, termed MGLP_1, and evaluated its ability to ameliorate obesity in a high-fat/high-sugar diet (HFSD)-induced mouse model. Eight-wk MGLP_1 treatment notably reduced obesity, as reflected by significant changes of body weight, serum triglyceride level, fatty liver and adipose tissue distribution. Amelioration of HFSD-induced gut dysbiosis by MGLP_1 was evidenced by reduced abundance ratio of bacterial phyla Firmicutes to Bacteroidetes, enhanced abundance of beneficial probiotic genera (Bifidobacterium, Lachnospiraceae, Ileibacterium), and reduced abundance of harmful genera (Clostridium, Romboutsia). Mechanisms of weight loss were investigated by comparing effects of treatment with MGLP_1 vs. prebiotics manno-oligosaccharides (MOS). MGLP_1 ameliorated gut microbiota imbalance by enhancing carbohydrate catabolism, whereas MOS promoted glycan synthesis and metabolism. Our findings, taken together, indicate that MGLP_1 fusion peptide has strong potential for amelioration of obesity by modifying relationships between gut microbiota and lipid and glucose metabolism.

Increasing dietary SFA:MUFA ratio with low levels of LC-PUFA affected lipid metabolism, tissue fatty acid profile and growth of juvenile California Yellowtail (Seriola dorsalis)

Lipids rich in saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) are among the alternative sources reported to maintain growth and tissue fatty acid composition and, in some cases, reducing the long-chain polyunsaturated fatty acids (LC-PUFA) requirements. The present works aims to investigate the effects of different SFA:MUFA ratios on growth performance, tissue fatty acid composition, and the expression of crucial genes involved in the lipid metabolism of juvenile California Yellowtail (Seriola lalandi) fed diets with increasing SFA:MUFA ratios (1.6, 1.8, and 2.0) with low LC-PUFA levels. After eight weeks, fish fed the control diet outperformed the experimental feeds with increasing SFA:MUFA ratio in terms of final weight, specific growth rate, and liver index. No differences were observed in survival, viscerosomatic index, and condition factor across dietary treatments. Whole-body, liver, and muscle tissues proximate composition was slightly affected by increasing the dietary SFA:MUFA ratio. In terms of fatty acid composition, whole-body, liver, and muscle tissues reflected the dietary fatty acid composition to most extent, except SFA (mainly 16:0) that was not proportionally deposited. LC-PUFA sparing effect was demonstrated at a low degree in this study, likely due to the low SFA:MUFA ratio or high content of dietary MUFA. Significant changes were observed in the expression of genes related to lipid metabolism. The ppara and igf1 expression were higher in fish fed the Control diet than those fed SFA:MUFA 1.6 diet. Whereas the fish from SFA:MUFA 1.6 group displayed higher cptla expression compared to fish from SFA:MUFA 2.0.

Lipid Droplet-Specific Fluorescent Probe for In Vivo Visualization of Polarity in Fatty Liver, Inflammation, and Cancer Models.

Elucidating the intrinsic relationship between diseases and lipid droplet (LD) polarity remains a great challenge owing to the lack of the research on multiple disease models. Until now, the visualization of abnormal LD polarity in models of inflammation and clinical cancer patient samples has not been achieved. To meet the urgent challenge, we facilely synthesized a robust LD-specific and polarity-sensitive fluorescent probe (LD-TTP), which consists of a triphenylamine segment as an electron-donor group (D) and a pyridinium as an electron-acceptor moiety (A), forming a typical D-π-A molecular configuration. Owing to the unique intramolecular charge transfer effect, LD-TTP exhibits high sensitivity to polarity change in the linear range from Δf = 0.258 to 0.312, with over 278-fold fluorescence enhancement. Moreover, we revealed that LD-TTP possessed satisfactory ability for sensitively monitoring LD-polarity changes in living cells. Using LD-TTP, we first demonstrated the detection of LD-polarity changes in fatty liver tissues and inflammatory living mice via confocal laser scanning fluorescence imaging. Surprisingly, the visualization of LD polarity has been achieved not only at the cellular levels and living organs but also in surgical specimens from cancer patients, thus holding great potential in the clinical diagnosis of human cancer. All these features render LD-TTP an effective tool for medical diagnosis of LD polarity-related diseases.

Contrast-enhanced ultrasound and its differential diagnosis in 21 patients with intrahepatic space-occupying lesions under the background of fatty liver.

The sonographic appearance in intrahepatic space-occupying lesions under the background of fatty liver is atypical. This study aimed to explore the value of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of intrahepatic space-occupying lesions under the background of fatty liver. Twenty-one patients with intrahepatic space-occupying lesions under the background of fatty liver who were treated in our hospital from January 2017 to September 2020 and met the inclusion/ exclusion criteria were enrolled in this study. The clinical and imaging data, size, location, shape, and other characteristics of the lesions were analyzed. The accuracy of conventional ultrasound and contrast-enhanced ultrasound in diagnosing intrahepatic space-occupying lesions under the background of fatty liver were compared. The 21 patients had moderate to severe fatty liver, including 11 cases with malignant lesions (52.38%) and 10 cases with benign lesions (47.62%). The accuracy of CEUS (90.48%) was significantly higher than that of conventional ultrasound (61.90%) in diagnosing intrahepatic space-occupying lesions under the background of fatty liver. A total of 33 lesions were detected in 21 patients, which were hypoechoic. Liver abscesses mainly showed ring-shaped enhancement in the arterial phase and low enhancement in the portal phase, with abscess necrosis in the center and no significant enhancement. Liver cyst lesions showed no significant enhancement in the arterial, portal, and delayed phases. The three stages of focal fat loss were synchronized and simultaneously enhanced with surrounding fatty liver tissues. The area under the diagnostic curve of conventional ultrasound and CEUS was 0.668 and 0.809, respectively, and the area under the curve of CEUS detection was the largest (P<0.05). CEUS can effectively improve the diagnostic accuracy of intrahepatic space-occupying lesions under the background of fatty liver, and is an effective means to differentially diagnose intrahepatic space-occupying lesions under the background of fatty liver.

Pubertal FGF21 deficit is central in the metabolic pathophysiology of an ovine model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), affecting over 10% of women, is associated with insulin resistance, obesity, dyslipidaemia, fatty liver and adipose tissue dysfunction. Its pathogenesis is poorly understood and consequently treatment remains suboptimal. Prenatally androgenized (PA) sheep, a clinically realistic model of PCOS, recapitulate the metabolic problems associated with PCOS. Fibroblast Growth Factor 21 (FGF21) is a metabolic hormone regulating lipid homeostasis, insulin sensitivity, energy balance and adipose tissue function. We therefore investigated the role of FGF21 in the metabolic phenotype of PA sheep. In adolescence PA sheep had decreased hepatic expression and circulating concentrations of FGF21. Adolescent PA sheep show decreased FGF21 signalling in subcutaneous adipose tissue, increased hepatic triglyceride content, trend towards reduced fatty acid oxidation capacity and increased hepatic expression of inflammatory markers. These data parallel studies on FGF21 deficiency, suggesting that FGF21 therapy during adolescence may represent a treatment strategy to mitigate metabolic problems associated with PCOS.

Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study

BackgroundWe sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals.MethodsThis was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU.ResultsIn the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (−76.9 HU vs. −73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10–2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21–2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score).ConclusionsMetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification.Trial registration NCT00927693.