Zebrafish are an ideal model organism to study lipid metabolism and to elucidate the molecular underpinnings of human lipid-associated disorders. Unlike murine models, to which various standardized high lipid diets such as a high-cholesterol diet (HCD) are available, there has yet to be a uniformly adopted zebrasfish HCD protocol. In this study, we have developed an improved HCD protocol and thoroughly tested its impact on zebrafish lipid deposition and lipoprotein regulation in a dose- and time- dependent manner. The diet stability, reproducibility, and fish palatability were also validated. Fish fed HCD developed hypercholesterolemia as indicated by significantly elevated ApoB-containing lipoproteins (ApoB-LP) and increased plasma levels of cholesterol and cholesterol esters. Feeding of the HCD to larvae for 8 days produced hepatic steatosis that become more stable and severer after 1 day of fasting and was associated with an opaque liver phenotype (dark under transmitted light). Unlike larvae, adult fish fed HCD for 14 days followed by a 3 day fast did not develop a stable fatty liver phenotype, though the fish had higher ApoB-LP levels in plasma and an up-regulated lipogenesis gene fasn in adipose tissue. In conclusion, our HCD zebrafish protocol represents an effective and reliable approach for studying the temporal characteristics of the physiological and biochemical responses to high levels of dietary cholesterol and provides insights into the mechanisms that may underlie fatty liver disease.

Acute pancreatitis is a severe inflammatory condition that can lead to systemic repercussions, one of which is the development of hepatic steatosis (fatty liver). The accumulation of fat in liver cells can complicate the course of pancreatitis, exacerbating inflammation and causing additional metabolic disturbances. The presence of fatty liver in the context of acute pancreatitis can thus worsen the overall clinical picture, making management more challenging and potentially leading to further complications. Here, we discuss a rare case of a 34-year-old female who demonstrated the reversal of fatty liver following the improvement of acute pancreatitis. This case highlights the dynamic relationship between acute pancreatitis and hepatic steatosis, illustrating that effective management of pancreatitis can lead to significant improvements in associated conditions such as fatty liver.

BACKGROUND: Data on the preoperative factors for bariatric surgery response in patients with morbid obesity are limited, and there are no studies on the relationship between myosteatosis and surgery response.
OBJECTIVE: We investigated the preoperative factors determining bariatric surgery response and the impact of preoperative muscle fat infiltration on bariatric surgery response.
METHODS: This retrospective longitudinal cohort study included 125 individuals (37 men, 88 women) with morbid obesity who underwent bariatric surgery. Muscle fat infiltration (skeletal muscle fat index [SMFI]) was evaluated using computed tomography-based psoas muscle mass and density at the 4th lumbar level. A bariatric surgery response was defined as ≥50% excessive weight loss at one year postoperatively.
RESULTS: Before bariatric surgery, the patient mean body weight and body mass index (BMI) were 107.0 kg and 39.0 kg/m2, respectively. After one year, the mean body weight was 79.6 kg. The mean excessive weight loss at one year was 75.6% and 102 (81.6%) patients were categorized as responders. There were no statistically significant differences in initial BMI, age, sex, or proportion of diabetes between responders and non-responders. Responders were more likely to have lower SMFI and triglyceride and glycated hemoglobin A1c levels than non-responders at baseline (P<0.05). Multiple logistic regression analysis showed that a lower baseline SMFI was associated with bariatric surgery response (odds ratio=0.31, 95% confidence interval=0.14-0.69, P=0.004).
CONCLUSIONS: Preoperative myosteatosis may determine the response to bariatric surgery.

UNASSIGNED: Hepatocellular carcinoma (HCC) incidence is increasing and correlated with metabolic dysfunction-associated steatotic liver disease (MASLD; formerly nonalcoholic fatty liver disease), even in patients without advanced liver fibrosis who are more likely to be diagnosed with advanced disease stages and shorter survival time, and less likely to receive a liver transplant. Machine learning (ML) tools can characterize large datasets and help develop predictive models that can calculate individual HCC risk and guide selective screening and risk mitigation strategies.
UNASSIGNED: Tableau and KNIME Analytics were used for descriptive analytics and ML tasks. ML models were developed using standard laboratory and clinical parameters. Sci-kit learn algorithms were used for model development. Data from University of California (UC), Davis, were used to develop and train a pilot predictive model, which was subsequently validated in an independent dataset from UC San Francisco. MASLD and HCC patients were identified by International Classification of Diseases-9/10 codes.
UNASSIGNED: Of the patients diagnosed with MASLD (n = 1561 training; n = 686 validation), HCC developed in 14% (n = 227) of the UC Davis training cohort and 25% (n = 176) of the UC San Francisco validation cohort. Liver fibrosis determined by the noninvasive Fibrosis-4 score was the strongest single predictor for HCC in the model. Using the validation cohort, the model predicted HCC development at 92.06% accuracy with an area under the curve of 0.97, F1-score of 0.84, 98.34% specificity, and 74.41% sensitivity.
UNASSIGNED: ML models can aid physicians in providing early HCC risk assessment in patients with MASLD. Further validation will translate to cost-effective, personalized care of at-risk patients.

UNASSIGNED: The obesity epidemic has increased the risk of nonalcoholic fatty liver disease (NAFLD) in both the general and chronic hepatitis B (CHB) populations. Our study aims to determine the prevalence of NAFLD in patients with CHB based on controlled attenuation parameter (CAP) and the epidemiological, clinical, and virological factors associated with severe hepatic steatosis.
UNASSIGNED: The Canadian Hepatitis B Network cohort was utilized to provide a cross-sectional description of demographics, comorbidities, antiviral treatment, and hepatits B virus (HBV) tests. Liver fibrosis and steatosis were measured by transient elastography and CAP, respectively. Any grade and severe steatosis were defined as CAP >248 and >280 dB/m, respectively. Advanced liver fibrosis was defined as transient elastography measurement >10.7 kPa.
UNASSIGNED: In 1178 patients with CHB (median age: 47.4%, 57.7% males, 75.7% Asian, 13% African, 6.5% White, 86% HBV e antigen negative, median HBV DNA of 2.44 log10IU/mL, 42.7% receiving treatment), the prevalence of any grade and severe steatosis was 53% and 36%, respectively. In the multivariate analysis, obesity was a significant predictor for severe steatosis (adjusted odds ratio: 5.046, 95% confidence interval: 1.22-20.93). Severe steatosis was a determinant associated with viral load (adjusted odds ratio: 0.385, 95% confidence interval: 0.20-0.75, P < .01; r = -0.096, P = .007) regardless of antiviral therapy, age, and alanine aminotransferase levels.
UNASSIGNED: In this large multiethnic CHB population, hepatic steatosis is common. Severe steatosis is independently associated with higher fibrosis, but negatively with HBV DNA, regardless of antiviral therapy history.

[This corrects the article DOI: 10.3389/fendo.2024.1349524.].

BACKGROUND: Ginseng berry (GB) has previously been demonstrated to improve systemic insulin resistance and regulate hepatic glucose metabolism and steatosis in mice with diet-induced obesity (DIO).
OBJECTIVE: In this study, the role of GB in metabolism was assessed using metabolomics analysis on the total liver metabolites of DIO mice.
METHODS: Metabolomic profiling was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF/MS) of liver tissue from mice on a 12-wk normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with 0.1% GB (HFD + GB). The detected metabolites, its pathways, and functions were analyzed through partial least square discriminant analysis (PLS-DA), the small molecular pathway database (SMPDB), and MetaboAnalyst 5.0.
RESULTS: The liver metabolite profiles of NC, HFD, and GB-fed mice (HFD + GB) were highly compartmentalized. Metabolites involved in major liver functions, such as mitochondrial function, gluconeogenesis/glycolysis, fatty acid metabolism, and primary bile acid biosynthesis, showed differences after GB intake. The metabolites that showed significant correlations with fasting blood glucose (FBG), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were highly associated with mitochondrial membrane function, energy homeostasis, and glucose metabolism. Ginseng berry intake increased the levels of metabolites involved in mitochondrial membrane function, decreased the levels of metabolites related to glucose metabolism, and was highly correlated with metabolic phenotypes.
CONCLUSIONS: This study demonstrated that long-term intake of GB changed the metabolite of hepatosteatotic livers in DIO mice, normalizing global liver metabolites involved in mitochondrial function and glucose metabolism and indicating the potential mechanism of GB in ameliorating hyperglycemia in DIO mice.

UNASSIGNED: Pediatric obesity is closely associated with cardiometabolic comorbidities, but the role of sex in this relationship is less investigated. We aimed to evaluate sex-related differences on cardiometabolic risk factors and preclinical signs of target organ damage in adolescents with overweight/obesity (OW/OB).
UNASSIGNED: The main cross-sectional study included 988 adolescents (510 boys and 478 girls) with OW/OB aged 10-18 years. In all youths clinical and biochemical variables were evaluated and an abdominal echography was performed. Echocardiographic data for the assessment of left ventricular mass (LVM) and relative wall thickness (RWT) were available in an independent sample of 142 youths (67 boys and 75 girls), while echographic data of carotid intima media thickness (cIMT) were available in 107 youths (59 boys and 48 girls).
UNASSIGNED: The three samples did not differ for age, body mass index, and sex distribution. In the main sample, boys showed higher waist-to-height ratio (WHtR) values (p < 0.0001) and fasting glucose levels (p = 0.002) than girls. Lower levels of estimates glomerular filtration rate (eGFR) were found in girls vs boys (p < 0.0001). No sex-related differences for prediabetes and hyperlipidemia were observed. A higher prevalence of WHtR ≥ 0.60 (57.3% vs 49.6%, p = 0.016) and fatty liver disease (FLD) (54.5% vs 38.3%, p < 0.0001) as well as a trend for high prevalence of hypertension (40.4 vs 34.7%, p = 0.06) were observed in boys vs girls. More, a higher prevalence of mild reduced eGFR (MReGFR) ( < 90 mL/min/1.73 m 2 ) was observed in girls vs boys (14.6% vs 9.6 %, p < 0.0001). In the sample with echocardiographic evaluation, boys showed higher levels of LVM (p = 0.046), and RWT (p = 0.003) than girls. Again, in the sample with carotid echography, boys showed higher levels of cIMT as compared to girls (p = 0.011).
UNASSIGNED: Adolescent boys with OW/OB showed higher risk of abdominal adiposity, FLD, and increased cardiac and vascular impairment than girls, whereas the latter had a higher risk of MReGFR. Risk stratification by sex for cardiometabolic risk factors or preclinical signs of target organ damage should be considered in youths with OW/OB.

Non-alcoholic fatty liver disease (NAFLD) is a common long-lasting liver disease that affects millions of people around the world. It is best identified with a hepatic fat build-up that ultimately leads to inflammation and damage. The classification and nomenclature of NAFLD have long been a controversial topic, until 2020 when a group of international experts recommended substituting NAFLD with MAFLD (metabolic dysfunction-associated FLD). MAFLD was then terminologically complemented in 2023 by altering it to MASLD, i.e., metabolic dysfunction-associated steatotic liver disease (MASLD). Both the MAFLD and the MASLD terminologies comprise the metabolic element of the disorder, as they offer diagnostic benchmarks that are embedded in the metabolic risk factors that underlie the disease. MASLD (as a multisystemic disease) provides a comprehensive definition that includes a larger population of patients who are at risk of liver morbidity and mortality, as well as adverse cardiovascular and diabetes outcomes. MASLD highlights metabolic risks in lean or normal weight individuals, a factor that has not been accentuated or discussed in previous guidelines. Novel antihyperglycemic agents, anti-hyperlipidemic drugs, lifestyle modifications, nutritional interventions, and exercise therapies have not been extensively studied in MAFLD and MASLD. Nutrition plays a vital role in managing both conditions, where centralizing on a diet rich in whole vegetables, fruits, foods, healthy fats, lean proteins, and specific nutrients (e.g., omega-3 fatty acids and fibers) can improve insulin resistance and reduce inflammation. Thus, it is essential to understand the role of nutrition in managing these conditions and to work with patients to develop an individualized plan for optimal health. This review discusses prevention strategies for NAFLD/MAFLD/MASLD management, with particular attention to nutrition and lifestyle correction.

Large-scale mortality events have occurred during the winter in Atlantic salmon sea cages in Eastern Canada and Iceland. Thus, in salmon held at 3 °C that were apparently healthy (i.e., asymptomatic) and that had \'early\' and \'advanced\' symptoms of \'winter syndrome\'/\'winter disease\' (WS/WD), we measured hepatic lipid classes and fatty acid levels, and the transcript expression of 34 molecular markers of fatty liver disease (FLD; a clinical sign of WS/WD). In addition, we correlated our results with previously reported characteristics associated with this disease\'s progression in these same individuals. Total lipid and triacylglycerol (TAG) levels increased by ~50%, and the expression of 32 of the 34 genes was dysregulated, in fish with symptoms of FLD. TAG was positively correlated with markers of inflammation (5loxa, saa5), hepatosomatic index (HSI), and plasma aspartate aminotransferase levels, but negatively correlated with genes related to lipid metabolism (elovl5b, fabp3a, cd36c), oxidative stress (catc), and growth (igf1). Multivariate analyses clearly showed that the three groups of fish were different, and that saa5 was the largest contributor to differences. Our results provide a number of biomarkers for FLD in salmon, and very strong evidence that prolonged cold exposure can trigger FLD in this ecologically and economically important species.