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Edible algae Neopyropia yezoensis is used as “Nori”, its dried sheet product, in Japanese cuisine. Its lipid components reportedly improve hepatic steatosis in obese db/db mice. In this study, we prepared “Nori powder (NP)” and “fermented Nori powder (FNP)” to utilize the functional lipids contained in “Nori” and examined their nutraceutical effects in vivo. Male db/db mice were fed a basal AIN-76 diet, a 10% NP-supplemented diet, or a 10% FNP-supplemented diet for 4 weeks. We detected eicosapentaenoic acid (EPA) present in both NP and FNP in the serum and liver of db/db mice in a dose-dependent manner. The NP diet reduced hepatic triglyceride accumulation (by 58%) in db/db mice by modulating gene expression, which resulted in the inhibition of lipogenic enzyme activity. Additionally, NP intake significantly suppressed the expression of inflammatory genes in the liver and hepatic injury marker levels in the sera (by 26%) of db/db mice. The FNP diet also led to a marked reduction in hepatic triglyceride accumulation (by 50%) and hepatic injury (by 28%) in db/db mice, and the mechanism of these alleviative actions was similar to that of the NP diet. Although the EPA content of FNP was one-third that of NP, metabolomic analysis revealed that bioactive betaine analogs, such as stachydrine, betaine, and carnitine, were detected only in FNP. In conclusion, we suggest that (1) mechanical processing of “Nori” makes its lipid components readily absorbable by the body to exert their lipid-lowering effects, and (2) fermentation of “Nori” produces anti-inflammatory molecules and lipid-lowering molecules, which together with the lipid components, can exert hepatic steatosis-alleviating effects.

The prevalence of fatty liver disease (FLD) is increasing. To clarify risk factors for developing FLD, we analyzed a database from healthy Japanese adults who had annual medical check-ups in 2004 and reexamined in 2009. We used the fatty liver index (FLI) to classify participants as FLD (FLI ≥60), borderline FLD (30≤ FLI <60), and normal liver (FLI <30). Subjects with hepatitis B or C virus infection and subjects with FLD at the baseline were excluded. The cumulative incidence of FLD from normal liver and from borderline FLD over five years were 0.65% (52/8,025) and 12.9% (244/1,888), respectively. After multiple adjustments, higher serum uric acid (SUA) (OR:1.92; 95% CI:1.40–2.63) and increased SUA change (OR:3.734; 95% CI:2.57–5.42) became risk factors for developing FLD from normal liver, as well as younger age and higher body mass index. The risk factors for developing FLD from borderline FLD were similar. Not only higher baseline SUA but also increased SUA change became independent risks for developing FLD.

Background Living donor liver transplantation using hepatic steatosis-improved grafts mitigates donor shortage. Herein, we aimed to evaluate the safety and feasibility of right-lobe adult-to-adult living donor liver transplantation using grafts improved through donor weight loss. Methods In this retrospective study conducted in a single institution in the Republic of Korea, we reviewed the medical records of living liver donors who lost ≥ 10% of their body weight to improve steatosis before right lobe donation between January 2015 and December 2020. Overall, 1040 right-lobe donors were included, with 150 and 890 donors in the weight loss and control (non-steatosis) groups, respectively. Results We performed 1:1 individual matching using the greedy matching method, by which 124 patients were included in each group. The median period from the date of the first visit to donation was 113 (interquartile range: 78–184) days in the weight loss group. As body weight changed from 82.8 ± 13.7 kg to 70.8 ± 11.8 kg ( p  < 0.0001), body mass index also improved from 27.8 ± 3.9 kg/m 2 to 23.8 ± 3.1 kg/m 2 ( p  < 0.0001). No significant between-group differences existed in the postoperative laboratory data for living donors and recipients. The incidence of postoperative complications in donors was comparable between the groups (control group, 9.7%; weight loss group, 13.7%; p  = 0.3185). The graft and recipient survival rates were comparable between the groups ( p  = 1.000). Conclusion Weight loss through diet and exercise significantly could improve hepatic steatosis in living donor candidates for liver transplantation, with the surgical outcomes in recipients and donors being equivalent to those in recipients and non-steatotic donors.

To evaluate the diagnostic performance of ultrasound-derived fat fraction (UDFF) and clinical prediction models in assessing hepatic steatosis grades in MASLD patients, with liver biopsy as reference standard.A total of 85 obese patients who were found to have fatty liver by B-mode ultrasound and underwent UDFF measurement, with liver biopsy available, were enrolled. The diagnostic performance of UDFF, clinical prediction models including fatty liver index (FLI), hepatic steatosis index (HSI), ZheJiang University index (ZJU index) and lipid accumulation product (LAP) for hepatic steatosis was assessed. The areas under receiver operating characteristics curves (AUROCs) were utilized to determine the diagnostic efficacy. DeLong test was used to compare the diagnostic performance of different noninvasive methods for hepatic steatosis. The UDFF values of S1, S2 and S3 groups were 17.53 ± 7.49%, 25.00 ± 5.41% and 27.58 ± 6.55%, respectively (P < 0.001). UDFF values were significantly positively correlated with histologic steatosis grades (r = 0.531, P < 0.001). In the ≥ S2 group, the AUROC of UDFF was higher than that of FLI and LAP (P < 0.05), but not significantly different from that of HSI and ZJU index (P > 0.05). In the ≥ S3 group, the AUROC of UDFF was higher than that of FLI, ZJU index and LAP (P < 0.05), but not significantly different from that of HSI (P > 0.05). The UDFF proves effective in assessing hepatic steatosis in patients with MASLD, and its diagnostic efficacy exceeded that of FLI and LAP, but there was no significant difference with HSI, ZJU index in the ≥ S2 group, and with HSI in the ≥ S3 group.

The noninvasive diagnosis of hepatic steatosis is of increasing concern. This study investigated the association of hepatic steatosis determined by non-enhanced CT criteria with clinical parameters in a screening population. Asymptomatic patients who underwent abdominal CT at our healthcare center were retrospectively analyzed (n = 339). Two radiologists measured the attenuation values of the liver parenchyma and spleen using non-enhanced CT images. CT criteria for hepatic steatosis were (a) absolute liver attenuation value <48 Hounsfield units (HU), (b) liver-to-spleen attenuation ratio <0.8, and (c) attenuation difference between the liver and spleen <−10. Body mass index (BMI) and hepatic steatosis index (HSI) were calculated, and laboratory findings were recorded. The association of hepatic steatosis with clinical parameters was assessed using univariate and logistic regression analyses. The presence of hepatic steatosis was significantly associated with the levels of serum fasting glucose and triglycerides, the alanine aminotransferase to aspartate aminotransferase (ALT/AST) ratio, BMI, and HSI values using any of the CT criteria. Logistic regression analysis revealed that the serum fasting glucose level and HSI were significantly associated with hepatic steatosis using criterion (a), while the ALT/AST ratio and HSI were associated with hepatic steatosis using criteria (b) and (c). The presence of hepatic steatosis on non-enhanced CT should be considered to indicate possible clinical profile abnormalities regarding metabolic syndrome.

Background/Objectives: Patients with isolated adult-onset growth hormone (GH) deficiency may present with hepatic steatosis and metabolic dysfunction. The effect of replacement therapy on metabolic phenotype has not been exhaustively studied yet. Methods: Patients with isolated adult-onset GH deficiency (GHD) were enrolled and prescribed GH-replacement therapy. DEXA scans for assessing body composition, anthropometric and biochemical parameters were evaluated at baseline and after 12 months of therapy. A fatty liver index, hepatic steatosis index and Fibrosis 4-test were calculated at baseline and after 12 months of therapy. Results and Conclusions: In our cohort, GH replacement therapy in adults with isolated adult-onset GHD is associated with weight loss and reduction of BMI (p < 0.001), amelioration in body composition with reduction in fat mass and trunk fat (respectively, p = 0.023 and p = 0.02), amelioration in lipid profile (significant reduction of total and LDL cholesterol and increase in HDL cholesterol) and reduction in fatty liver index (p = 0.021). Further long-term, randomized studies with bigger cohorts and advanced diagnostics are needed to confirm these results of our exploratory study.

Adzuki bean is well known as a potential functional food that improves metabolic complications from obesity and diabetes. Lipocalin-2 (LCN2) has been implicated to have an important role in obesity and diabetes. However, the protective roles of adzuki bean MY59 extract (ABE) on insulin resistance and hepatic steatosis are not fully understood. In the present study, we investigated the effects of ABE on LCN2 expression in high-fat diet (HFD)-fed mice. ABE reduced HFD-induced fat mass and improved insulin resistance. In addition to hepatic steatosis, HFD-fed mice showed many apoptotic cells and neutrophils in the epididymal fat pads. However, these findings were significantly reduced by ABE supplementation. In particular, we found that increased LCN2 proteins from serum, epididymal fat pads, and liver in HFD-fed mice are significantly reduced by ABE. Furthermore, ABE reduced increased heme oxygenase-1 and superoxide dismutase-1 expressions in adipose tissue and liver in HFD-fed mice. We found that hepatic nuclear factor-kappa B (NF-κB) p65 expression in HFD-fed mice was also reduced by ABE. Thus, these findings indicate that ABE feeding could improve insulin resistance and hepatic steatosis by decreasing LCN2-mediated inflammation and oxidative stress in HFD-fed mice.

Ultrasound imaging is a first-line assessment tool for hepatic steatosis. Properties of tissue microstructures correlate with the statistical distribution of ultrasound backscattered signals, which can be described by the Nakagami distribution (a widely adopted approximation of backscattered statistics). The double Nakagami distribution (DND) model, which combines two Nakagami distributions, was recently proposed for using high-frequency ultrasound to analyze backscattered statistics corresponding to lipid droplets in the fat-infiltrated liver. This study evaluated the clinical feasibility of the DND model in ultrasound parametric imaging of hepatic steatosis by conducting clinical experiments using low-frequency ultrasound dedicated to general abdominal examinations. A total of 204 patients were recruited, and ultrasound image raw data were acquired using a 3.5 MHz array transducer for DND parametric imaging using the sliding window technique. The DND parameters were compared with hepatic steatosis grades identified histologically. A receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic performance. The results indicated that DND parametric imaging constructed using a sliding window with the side length of five times the pulse length of the transducer provided stable and reliable DND parameter estimations and visualized changes in the backscattered statistics caused by hepatic steatosis. The DND parameter increased with the hepatic steatosis grade. The areas under the ROC curve for identifying hepatic steatosis were 0.76 (≥mild), 0.81 (≥moderate), and 0.82 (≥severe). When using low-frequency ultrasound, DND imaging allows the clinical detection of hepatic steatosis and reflects information associated with lipid droplets in the fat-infiltrated liver.

The purpose of this study was to prospectively evaluate whether monitoring hepatic steatosis by ultrasonography with acoustic structure quantification (ASQ) is feasible, using magnetic resonance spectroscopy (MRS) as the reference standard. Thirty-six patients with suspected fatty liver disease underwent both untrasonography with ASQ and MRS on the same day. After a mean follow-up period of 11.4±2.5 months, follow-up ultrasonography with ASQ and MRS were performed on 27 patients to evaluate whether hepatic steatosis had improved. The focal disturbance (FD) ratio, as calculated using ASQ, and the hepatic fat fraction (HFF), estimated by MRS, were obtained at both initial and follow-up examinations. Pearson correlation coefficients were calculated to assess the correlations between ordinal values. The FD ratio showed a strong, negative linear correlation with the HFF after logarithmic transformation of both variables from the initial examinations of 36 patients (ρ=-0.888, P<0.001) and the follow-up examinations of 27 patients (ρ=-0.920, P<0.001). There was also a significant, negative linear correlation between the change in the logarithm of the FD ratio and the change in the logarithm of the HFF by MRS over the follow-up period (ρ=-0.645, P<0.001). In 16 patients with an increased FD ratio on follow-up, the HFF on follow-up MRS significantly decreased, and high-density lipoprotein levels significantly increased, whereas low-density lipoprotein levels tended to decrease. The FD ratio was significantly correlated with the HFF at both the initial and follow-up examinations, and there was also a significant correlation between changes in the FD ratio and changes in the HFF over the follow-up period.

Protective effects of s-methyl cysteine (SMC) alone, protocatechuic acid (PCA) alone, and SMC plus PCA against chronic ethanol consumption induced hepatic steatosis and inflammation were investigated. Mice were divided into six groups: normal diet (ND) group, Lieber-DeCarli liquid diet without ethanol (LD diet) group, LD diet with ethanol (LED diet) group, SMC group (LED diet plus 0.25% SMC), PCA group (LED diet plus 0.25% PCA), and SMC+PCA group (LED diet plus 0.125% SMC + 0.125% PCA). After 8 weeks of supplementation, blood and liver were used for analysis. Biochemical and histological data showed that SMC plus PCA led to a greater reduction in lipid droplets in the liver than SMC or PCA treatment alone. SMC plus PCA resulted in greater suppression in hepatic mRNA expression of peroxisome proliferator-activated receptor-gamma, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase-1, cyclooxygenase-2, and myeloperoxidase than SMC or PCA treatment alone. SMC plus PCA led to a greater decrease in hepatic reactive oxygen species and inflammatory cytokine levels than SMC or PCA treatment alone. These novel findings suggest that the combination of SMC and PCA was a potent remedy for alcoholic liver disorders.