Fatty Liver Index and Skeletal Muscle Density

Accumulation of fat in the liver and skeletal muscle is associated with obesity and poor health outcomes. Liver steatosis is a characteristic of non-alcoholic fatty liver disease (NAFLD) and myosteatosis, of poor muscle quality in sarcopenia. In this study of 403 men (33–96 years), we investigated associations between the fatty liver index (FLI) and muscle density, as markers of fat accumulation in these organs. We also investigated associations between the FLI and parameters of sarcopenia, including DXA-derived appendicular lean mass (ALM) and handgrip strength by dynamometry. Muscle density was measured using pQCT at the radius and tibia. FLI was calculated from BMI, waist circumference, and levels of triglycerides and gamma-glutamyltransferase. There was a pattern of decreasing muscle density across increasing quartiles of FLI. After adjusting for age and lifestyle, mean radial muscle density in Q4 was 2.1% lower than Q1 (p < 0.001) and mean tibial muscle density was 1.8% lower in Q3 and 3.0% lower in Q4, compared to Q1 (p = 0.022 and < 0.001, respectively). After adjusting for age and sedentary lifestyle, participants in the highest FLI quartile were sixfold more likely to have sarcopenia. In conclusion, our results suggest that fat accumulation in the liver co-exists with fat infiltration into skeletal muscle.

Formulation of Huangqin Decoction Influence Immune Function and Fecal Microbiome of Chicks Suffered Escherichia Coli O78 Challenge

Ethnopharmacological relevance: Huangqin Decoction (HQD), a traditional Chinese medicine formula from the Shang Han Lun written by Zhang Zhongjing, has been used in China for nearly two thousand years. According to traditional Chinese medicine and a previous literature, HQD has the effect of clearing heat and removing toxin, antidiarrhea, and relieving pain. Therefore, HQD were used to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. Materials and methods: HQD consist of four components: Scutellariae Radix (huangqin, HQ), Paeoniae Radix Alba (shaoyao, SY), Jujubae Fructus (dazao, DZ), Licorice (gancao, GC). A total of 80 1-day-old male Esa brown chicks were divided into eight groups (n=10): Control group (CG), model group (MG), Enrofloxacin group (ENR, 10 mg/kg·BW), HQD group (HQD, 500 mg/kg·BW), HQD-GC group (GC absent HQD, 500 mg/kg·BW), HQD-HQ group (HQ absent HQD, 500 mg/kg·BW), HQD-DZ group (DZ absent HQD, 500 mg/kg·BW) and HQD-SY group (SY absent HQD, 500 mg/kg·BW). The chicks, which were given HQD, herb absent HQD, or enrofloxacin orally at 19 days of age for 7 days, and then were intraperitoneally injected with inoculum of E. coli O78，fed continuously for 5 days as before. Results: It showed that E. coli O78 challenge decreased the average daily gain (ADG) and increased the mortality rate of chicks, increased the heart index and the liver index, decreased the bursal index, and had no effect on the spleen index. E. coli O78 challenge increased the serum lysozyme (LZM) and IL-1β, TNF-α, IL-10, IL-6, up-regulated the mRNA expression of TLR4, TLR5 and TLR15 in the spleen, and had no effect on the bursal compared with CG. E. coli O78 challenge increased the Operational Taxonomic Unit (OTU), increased the relative abundance of harmful bacteria Proteobacteria, and decreased the relative abundance of probiotics Bacteroidetes and Firmicutes at the phylum levels. E. coli O78 challenge increased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas at the genus levels. HQD supplementation showed higher ADG and reduced the mortality rate caused by E. coli O78 challenge, decreased the heart index and liver index, and increased the bursal index and spleen index. HQD supplementation decreased the serum LZM, IL-1β, TNF-α, IL-10, IL-6 levels, down-regulated the mRNA expression of TLR4, TLR5 and TLR15 in the spleen in E. coli O78 challenged chicks, and up-regulated the mRNA expression of TLR4, TLR5 and TLR15 in the bursal in that. At the phylum levels, HQD supplementation reversed the increased of OTUs, decreased the relative abundance of harmful bacteria Proteobacteria, increased the relative abundance of probiotics Bacteroidetes and Firmicutes. At the genus levels, HQD decreased the relative abundance of harmful bacteria Escherichia-Shigella and Pseudomonas. It means that HQD reversed the change of the gut microbiota structure. Compared with HQD, HQD-DZ and HQD-HQ increased the mortality rate. HQD-HQ decreased the ADG and liver index. HQD-GC decreased the spleen index. HQD-DZ, HQD-HQ, HQD-SY and HQD-GC increased the serum TL-6, but only the HQD-HQ and HQD-SY increased the serum TNF-α. All herb absent HQD did not activate the toll-like receptors signaling pathways in spleen and bursal of chicks. HQD-DZ and HQD-HQ increased the harmful bacteria Escherichia-Shigella, and HQD-DZ increased the harmful bacteria Proteobacteria levels. Conclusions: Dietary supplementation with HQD, by down-regulating the mRNA expression of TLR4, TLR5 and TLR15 in the spleen, further decreasing the serum LZM and IL-1β, TNF-α, IL-10, IL-6 levels, improves the immune function and reverse the change of fecal microbiome in chicks challenged with E. coli O78. About herb absent groups, the results shown that SY and DZ play a key role in reducing the level of inflammatory factors and keeping fecal microbiome balance respectively. what’s more, we highlighted that HQ is indispensable in HQD, HQ not only play a key role in reducing the level of inflammatory factors, but also keep the balance of fecal microflora.

Prediction of Liver Weight Recovery by an Integrated Metabolomics and Machine Learning Approach After 2/3 Partial Hepatectomy

Liver has an ability to regenerate itself in mammals, whereas the mechanism has not been fully explained. Here we used a GC/MS-based metabolomic method to profile the dynamic endogenous metabolic change in the serum of C57BL/6J mice at different times after 2/3 partial hepatectomy (PHx), and nine machine learning methods including Least Absolute Shrinkage and Selection Operator Regression (LASSO), Partial Least Squares Regression (PLS), Principal Components Regression (PCR), k-Nearest Neighbors (KNN), Support Vector Machines (SVM), Random Forest (RF), eXtreme Gradient Boosting (xgbDART), Neural Network (NNET) and Bayesian Regularized Neural Network (BRNN) were used for regression between the liver index and metabolomic data at different stages of liver regeneration. We found a tree-based random forest method that had the minimum average Mean Absolute Error (MAE), Root Mean Squared Error (RMSE) and the maximum R square (R2) and is time-saving. Furthermore, variable of importance in the project (VIP) analysis of RF method was performed and metabolites with VIP ranked top 20 were selected as the most critical metabolites contributing to the model. Ornithine, phenylalanine, 2-hydroxybutyric acid, lysine, etc. were chosen as the most important metabolites which had strong correlations with the liver index. Further pathway analysis found Arginine biosynthesis, Pantothenate and CoA biosynthesis, Galactose metabolism, Valine, leucine and isoleucine degradation were the most influenced pathways. In summary, several amino acid metabolic pathways and glucose metabolism pathway were dynamically changed during liver regeneration. The RF method showed advantages for predicting the liver index after PHx over other machine learning methods used and a metabolic clock containing four metabolites is established to predict the liver index during liver regeneration.

Fatty Liver Index for Predicting Nonalcoholic Fatty Liver Disease in an Asymptomatic Korean Population

Nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, highlighting the importance of early and accurate detection and the appropriate management of NAFLD. However, ultrasonography (US) is not included in many mass screening programs, and people have limited access to it. The aim of this study is to validate the fatty liver index (FLI) and investigate the optimal cutoff value for predicting NAFLD in an asymptomatic population. We conducted a retrospective cohort study in Korea. All subjects who underwent health checkup exams, including abdominal US, controlled attenuation parameter (CAP) and blood testing, were enrolled. Analyses of the area under the receiver operating characteristic curve (AUROC) were used to evaluate the diagnostic accuracy and to calculate the optimal FLI cutoff for US-NAFLD. Among the 4009 subjects (mean age 54.9 years, 83.5% male), the prevalence of US-diagnosed NAFLD and CAP-defined hepatic steatosis was 61.4% and 55.4%. The previously used cutoff of FLI = 60 showed poor performance in predicting US-diagnosed NAFLD, with an AUROC of 0.63 (0.62–0.64), and CAP-defined NAFLD, with an AUROC 0.63 (0.62–0.64). The optimal FLI cutoff values to discriminate fatty liver detected by US were 29 for the entire population, with an AUROC of 0.82 (0.81–0.84). The sex-specific values were 31 for males and 18 for females (sensitivity 72.8% and 73.4%; specificity 74.2% and 85.0%, respectively). The FLI cutoff for US-diagnosed NAFLD can be set as 29 for the entire Korean population. Considering the sex dimorphism in NAFLD, different cutoff values are suggested to predict US-diagnosed NAFLD. These results may be helpful in the accurate non-invasive diagnosis of NAFLD.

The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice

Background:Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI).Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl4) and the potential underlying mechanisms.Materials and Methods: Sixty adult mice were randomized into six study groups (n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined.Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1β, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI.Conclusion: ZDP has obvious protective effects on CCl4-induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair.

Reduced Rank Regression-Derived Dietary Patterns Related to the Fatty Liver Index and Associations with Type 2 Diabetes Mellitus among Ghanaian Populations under Transition: The RODAM Study

The Fatty Liver Index (FLI) is a proxy for the steatotic component of non-alcoholic fatty liver disease (NAFLD). For sub-Saharan African populations, the contribution of dietary factors to the development of NAFLD in the etiology of type 2 diabetes mellitus (T2DM) remains to be clarified. We identified sex-specific dietary patterns (DPs) related to the FLI using reduced ranked regression (RRR) and evaluated the associations of these DPs with T2DM. This analysis used data from the RODAM, a multi-center cross-sectional study of Ghanaian populations living in Ghana and Europe. The daily intake frequencies of 30 food groups served as the predictor variables, while the FLI was the response variable. The odds ratios and 95% confidence intervals for T2DM were calculated per one standard deviation increase in the DP score using logistic regression. In males, the DP score explained 9.9% of the variation in their food intake and 16.0% of the variation in the FLI. This DP was characterized by high intakes of poultry, whole-grain cereals, coffee and tea, condiments, and potatoes, and the chance of T2DM was 45% higher per 1 DP score-SD (Model 2). Our results indicate that the intake of modernized foods was associated with proxies of NAFLD, possibly underlying the metabolic pathways to developing T2DM.

Fatty Liver Index is Positively Associated with Arterial Stiffness in a Chinese Cohort Undergoing Health Assessment

Objective Nonalcoholic fatty fiver disease (NAFLD) is a metabolic liver injury closely related to insulin resistance. Fatty liver index (FLI) can be used as a surrogate marker and is a validated index for NAFLD. This study aimed to explore the relationship between FLI and arterial stiffness in a Chinese population. Methods From December 2017 to March 2019, 402 inpatients (mean age 51.12 ± 11.95 years) were recruited for cardiovascular disease screening at Ruijin Hospital North, Shanghai. Measurement of brachial systolic, diastolic, mean, and pulse pressure was done with cuff sphygmomanometry and carotid-femoral pulse wave velocity (cfPWV) was measured (SphygmoCor) to assess arterial stiffness. Results Subjects were divided into three groups according to their FLI < 30, normal; 30–59, intermediate fatty liver index; ≥ 60, NAFLD. The proportion of subjects with hepatic steatosis (FLI ≥ 60), intermediate FLI (30–59), and no steatosis (FLI < 30) was 34.4%, 31.8%, and 33.8%, respectively. The male population (53.9%) had significantly higher FLI levels (p < 0.05). Subjects with FLI ≥ 60 had higher cfPWV (8.41 ± 1.77 m/s) than those with FLI < 30 (7.81 ± 1.83 m/s; p = 0.006). cfPWV was positively correlated with logFLI (r = 0.168, p = 0.001). After adjusting for age, sex, body mass index, mean arterial blood pressure, glucose, cholesterol, heart rate, and glomerular filtration rate (eGFR), FLI remained positively associated with cfPWV (β = 0.097, p = 0.024). Conclusion cfPWV, as a measure of arterial stiffness, is higher in the NAFLD group when compared to that in normal groups. Fatty liver index is positively associated with arterial stiffness in a Chinese population.