Liver Expressed Antimicrobial Peptide 2 is Associated with Steatosis in Mice and Humans

Abstract Background and Aims Liver expressed antimicrobial peptide 2 (LEAP2) is recently identified as a regulator in energy metabolism. This study aims to 1) investigate the role of leap2 in hepatic steatosis in C57BL/6 mice; 2) evaluate the association between circulating LEAP2 levels and liver fat contents in a hospital based case-control study. Methods The rodent experiment: western blotting and qPCR were performed to evaluate leap2 levels, lipid metabolism pathways and insulin signaling. shRNA was used to knockdown leap2. The clinical study: commercial ELISA kits were used to measure circulating LEAP2 levels (validated by western blotting). Liver fat content was estimated using MRI-derived proton density fat fraction and FibroScan-derived controlled attenuation parameter. Results The rodent experiment found the hepatic expression and secreted levels of leap2 were increased in mice with diet-induced steatosis. Leap2 knockdown ameliorated steatosis via lipolytic/lipogenic pathway and improved insulin sensitivity via IRS/AKT signaling. The clinical study reported increased circulating levels of LEAP2 in the subjects with steatosis. Moreover, LEAP2 correlated positively with age, body mass index, waist-to-hip ratio, liver fat content, fasting insulin and HOMA-IR, whereas inversely with acyl-ghrelin. Furthermore, the circulating levels of LEAP2 are dependent on liver fat content, acyl-ghrelin and fasting glucose. Lastly, circulating LEAP2 is an independent predictor of NAFLD. Conclusions The study suggests LEAP2 is associated with hepatic steatosis, which may involve lipolytic/lipogenic pathway and insulin signaling.

Download Full-text

Quantification of Hepatorenal Index for Computer-Aided Fatty Liver Classification with Self-Organizing Map and Fuzzy Stretching from Ultrasonography

BioMed Research International ◽

10.1155/2015/535894 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Kwang Baek Kim ◽

Chang Won Kim

Keyword(s):

Fatty Liver ◽

Hepatic Steatosis ◽

Learning Algorithm ◽

Fat Content ◽

Liver Fat ◽

Self Organizing Map ◽

Liver Fat Content ◽

Computer Aided ◽

Good Set ◽

Self Organizing

Accurate measures of liver fat content are essential for investigating hepatic steatosis. For a noninvasive inexpensive ultrasonographic analysis, it is necessary to validate the quantitative assessment of liver fat content so that fully automated reliable computer-aided software can assist medical practitioners without any operator subjectivity. In this study, we attempt to quantify the hepatorenal index difference between the liver and the kidney with respect to the multiple severity status of hepatic steatosis. In order to do this, a series of carefully designed image processing techniques, including fuzzy stretching and edge tracking, are applied to extract regions of interest. Then, an unsupervised neural learning algorithm, the self-organizing map, is designed to establish characteristic clusters from the image, and the distribution of the hepatorenal index values with respect to the different levels of the fatty liver status is experimentally verified to estimate the differences in the distribution of the hepatorenal index. Such findings will be useful in building reliable computer-aided diagnostic software if combined with a good set of other characteristic feature sets and powerful machine learning classifiers in the future.

Download Full-text

Noninvasive Quantification of Hepatic Steatosis: Relationship Between Obesity Status and Liver Fat Content

The Open Obesity Journal ◽

10.2174/1876823701406010016 ◽

2014 ◽

Vol 6 (1) ◽

pp. 16-24 ◽

Cited By ~ 3

Author(s):

S. C. McLeay ◽

G. A. Morrish ◽

T. K. Ponnuswamy ◽

B. Devanand ◽

M. Ramanathan ◽

...

Keyword(s):

Fatty Liver ◽

Hepatic Steatosis ◽

Liver Volume ◽

Fat Content ◽

Liver Fat ◽

Normal Body Mass Index ◽

Liver Fat Content ◽

Total Liver Volume ◽

Total Liver ◽

Obese Subjects

The aim of this study was to assess and compare fat content within the liver for normal (body mass index (BMI) < 25 kg/m2), overweight (25-30 kg/m2) and obese (≥ 30 kg/m2) subjects using a noninvasive, non-contrast computed tomography (CT) quantification method. Adult subjects aged 18-60 yrs scheduled to undergo CT examination of the abdominal region were recruited for this study, stratified across BMI categories. Liver volume, fat content, and lean liver volume were determined using CT methods. A total of 100 subjects were recruited, including 30 normal weight, 31 overweight, and 39 obese. Total liver volume increased with BMI, with mean values of 1138 ± 277, 1374 ± 331, and 1766 ± 389 cm3 for the normal, overweight, and obese, respectively (P < 0.001), which was due to an increase in both liver fat content and lean liver volume with BMI. Some obese subjects had no or minimal hepatic fat content. The prevalence of mild fatty liver in this study of 100 subjects was overestimated for all BMI categories using a range of qualitative diagnostic measures, with predicted prevalence of fatty liver in obese subjects ranging from 76.9% for liver-to-spleen ratio ≤ 1.1 to 89.7% for liver attenuation index (liver HU - spleen HU) ≤ 40, compared to 66.7% by quantification of fat content. Results show that total liver volume increases with BMI, however, not all obese subjects display fatty infiltration of the liver. CT quantification of liver fat content may be suitable for accurate diagnosis of hepatic steatosis in clinical practice and assessment of donor livers for transplantation.

Download Full-text

Associations of circulating chemerin and adiponectin concentrations with hepatic steatosis

Endocrine Connections ◽

10.1530/ec-19-0300 ◽

2019 ◽

Vol 8 (8) ◽

pp. 1097-1107 ◽

Cited By ~ 1

Author(s):

Lena-Maria Levin ◽

Henry Völzke ◽

Markus M Lerch ◽

Jens-Peter Kühn ◽

Matthias Nauck ◽

...

Keyword(s):

Hepatic Steatosis ◽

Liver Enzymes ◽

Experimental Studies ◽

Population Based ◽

Fat Content ◽

Liver Fat ◽

Liver Fat Content ◽

Logistic Regression Models ◽

Magnetic Resonance Imaging Mri ◽

Underlying Mechanisms

Objective Chemerin and adiponectin are adipokines assumed to be involved in the development of metabolic syndrome-related phenotypes like hepatic steatosis. We aimed to evaluate the associations of circulating chemerin and adiponectin concentrations with liver enzymes, liver fat content, and hepatic steatosis in the general population. Methods Data of 3951 subjects from the population-based Study of Health in Pomerania (SHIP-TREND) were used. Hepatic steatosis was assumed when either a hyperechogenic liver (assessed via ultrasound) or a magnetic resonance imaging (MRI)-quantified liver fat content >5% was present. Adjusted sex-specific quantile and logistic regression models were applied to analyze the associations of chemerin and adiponectin with liver enzymes, liver fat content and hepatic steatosis. Results The observed associations of chemerin and adiponectin with liver enzymes were very divergent depending on sex, fasting status and the specific enzyme. More consistent results were seen in the analyses of these adipokines in relation to MRI-quantified liver fat content. Here, we observed inverse associations to adiponectin in both sexes as well as a positive (men) or U-shaped (women) association to chemerin. Similarly, the MRI-based definition of hepatic steatosis revealed strongly consistent results: in both sexes, high chemerin concentrations were associated with higher odds of hepatic steatosis, whereas high adiponectin concentrations were associated with lower odds. Conclusion Our results suggest a role of these adipokines in the pathogenesis of hepatic steatosis independent of metabolic or inflammatory disorders. However, experimental studies are needed to further clarify the underlying mechanisms and the inter-play between adipokine concentrations and hepatic steatosis.

Download Full-text

External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance spectroscopy, to identify hepatic steatosis in healthy controls and obese, insulin-resistant individuals

Acta Endocrinologica ◽

10.1530/eje-14-0112 ◽

2014 ◽

Vol 171 (5) ◽

pp. 561-569 ◽

Cited By ~ 62

Author(s):

Daniel J Cuthbertson ◽

Martin O Weickert ◽

Daniel Lythgoe ◽

Victoria S Sprung ◽

Rebecca Dobson ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Fatty Liver ◽

Hepatic Steatosis ◽

Fat Content ◽

Liver Fat ◽

Resonance Spectroscopy ◽

Lipid Accumulation Product ◽

Liver Fat Content ◽

Fatty Liver Index

Background and aimsSimple clinical algorithms including the fatty liver index (FLI) and lipid accumulation product (LAP) have been developed as surrogate markers for non-alcoholic fatty liver disease (NAFLD), constructed using (semi-quantitative) ultrasonography. This study aimed to validate FLI and LAP as measures of hepatic steatosis, as determined quantitatively by proton magnetic resonance spectroscopy (1H-MRS).MethodsData were collected from 168 patients with NAFLD and 168 controls who had undergone clinical, biochemical and anthropometric assessment. Values of FLI and LAP were determined and assessed both as predictors of the presence of hepatic steatosis (liver fat >5.5%) and of actual liver fat content, as measured by 1H-MRS. The discriminative ability of FLI and LAP was estimated using the area under the receiver operator characteristic curve (AUROC). As FLI can also be interpreted as a predictive probability of hepatic steatosis, we assessed how well calibrated it was in our cohort. Linear regression with prediction intervals was used to assess the ability of FLI and LAP to predict liver fat content. Further validation was provided in 54 patients with type 2 diabetes mellitus.ResultsFLI, LAP and alanine transferase discriminated between patients with and without steatosis with an AUROC of 0.79 (IQR=0.74, 0.84), 0.78 (IQR=0.72, 0.83) and 0.83 (IQR=0.79, 0.88) respectively although could not quantitatively predict liver fat. Additionally, the algorithms accurately matched the observed percentages of patients with hepatic steatosis in our cohort.ConclusionsFLI and LAP may be used to identify patients with hepatic steatosis clinically or for research purposes but could not predict liver fat content.

Download Full-text

The relationship between Lipocalin-2 level and hepatic steatosis in obese patients with NAFLD after bariatric surgery

Lipids in Health and Disease ◽

10.1186/s12944-022-01622-0 ◽

2022 ◽

Vol 21 (1) ◽

Author(s):

Jiaqi Chen ◽

Shihui Lei ◽

Yueye Huang ◽

Xiaojuan Zha ◽

Lei Gu ◽

...

Keyword(s):

Hepatic Steatosis ◽

Fat Content ◽

Liver Fat ◽

Obese Patients ◽

Lipocalin 2 ◽

Liver Fat Content ◽

Nonalcoholic Fatty Liver ◽

Hepatic Fat ◽

Relationship Of ◽

The Relationship

Abstract Background Lipocalin-2 (LCN2) has a critical effect on obesity as well as its associated comorbidities. The present study focused on analyzing serum LCN2 levels of obese patients with nonalcoholic fatty liver disease (NAFLD) and on determining relationship of hepatic steatosis improvement with LCN2 levels after laparoscopic sleeve gastrectomy (LSG). Methods This work enrolled ninety patients with obesity and NAFLD. Twenty-three of them underwent LSG. Anthropometric and biochemical parameters and serum LCN2 levels were determined at baseline and those at 6-month post-LSG. Controlled attenuation parameter (CAP) measured by FibroScan was adopted for evaluating hepatic steatosis. Results Among severe obesity patients, serum LCN2 levels were significantly increased (111.59 ± 51.16 ng/mL vs. 92.68 ± 32.68 ng/mL, P = 0.035). The CAP value was higher indicating higher liver fat content (360.51 ± 45.14 dB/m vs. 340.78 ± 45.02 dB/m, P = 0.044). With regard to surgical patients, liver function, glucose, and lipid levels were significantly improved after surgery. Serum LCN2 levels significantly decreased (119.74 ± 36.15 ng/mL vs. 87.38 ± 51.65 ng/mL, P = 0.001). Decreased CAP indicated a significant decrease in liver fat content (358.48 ± 46.13 dB/m vs. 260.83 ± 69.64 dB/m, P < 0.001). The decrease in LCN2 levels was significantly related to the reduced hepatic fat content and improvement in steatosis grade after adjusting for gender, age, and BMI decrease. Conclusions Serum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement.

Download Full-text

Predicting hepatic steatosis and liver fat content in obese children based on biochemical parameters and anthropometry

Pediatric Obesity ◽

10.1111/ijpo.232 ◽

2014 ◽

Vol 10 (2) ◽

pp. 112-117 ◽

Cited By ~ 4

Author(s):

H-X. Zhang ◽

X-Q. Xu ◽

J-F. Fu ◽

C. Lai ◽

X-F. Chen

Keyword(s):

Hepatic Steatosis ◽

Biochemical Parameters ◽

Fat Content ◽

Liver Fat ◽

Obese Children ◽

Liver Fat Content

Download Full-text

Diabetes Remission Clinical Trial (DiRECT)—Plasma Liver Function Tests Reflect Change in Liver Fat Content in Early Type 2 Diabetes

Diabetes ◽

10.2337/db18-1834-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 1834-P

Author(s):

SVIATLANA V. ZHYZHNEUSKAYA ◽

AHMAD AL-MRABEH ◽

CARL PETERS ◽

ALISON C. BARNES ◽

KIEREN G. HOLLINGSWORTH ◽

...

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Liver Function ◽

Liver Function Tests ◽

Fat Content ◽

Diabetes Remission ◽

Liver Fat ◽

Early Type ◽

Liver Fat Content

Download Full-text

115-LB: Oral Insulin–Induced Reduction in Liver Fat Content in T2DM Patients with Nonalcoholic Steatohepatitis

Diabetes ◽

10.2337/db20-115-lb ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 115-LB

Author(s):

MIRIAM KIDRON ◽

SHARON PERLES ◽

REEM KALOTI ◽

RAMI GHANTOUS ◽

SUHA F. SANDOUKA ◽

...

Keyword(s):

Nonalcoholic Steatohepatitis ◽

Fat Content ◽

Liver Fat ◽

Oral Insulin ◽

Liver Fat Content

Download Full-text

Liver fat content is independently associated with microalbuminuria in a normotensive, euglycaemic Chinese population: a community-based, cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2020-044237 ◽

2021 ◽

Vol 11 (6) ◽

pp. e044237

Author(s):

Xiaoming Li ◽

Mingfeng Xia ◽

Hui Ma ◽

Yu Hu ◽

Hongmei Yan ◽

...

Keyword(s):

Logistic Regression ◽

Blood Glucose ◽

Density Lipoprotein ◽

Fat Content ◽

Lipoprotein Cholesterol ◽

Liver Fat ◽

Community Based ◽

Liver Fat Content ◽

Cross Sectional ◽

Multivariable Logistic Regression

ObjectiveNon-alcoholic fatty liver disease (NAFLD) is associated with microalbuminuria (MA) in patients with diabetes/pre-diabetes. Whether this association is mediated by blood glucose and blood pressure (BP) remains unclear. This study investigated whether liver fat content (LFC) was associated with MA in a normotensive and non-diabetic population.DesignA cross-sectional substudy.SettingsLFC was determined from the hepatic/renal echogenicity ratio at ultrasound. MA was defined as an albumin-to-creatinine ratio (ACR) of 30–300 µg/mg (early- morning urine sample). Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate LFC as a predictor of MA.ParticipantsBetween May 2010 and June 2011, this cross-sectional, community-based study enrolled residents from Shanghai (China), aged ≥40 years and with normal glucose tolerance and BP.ResultsA total of 550 residents (median age, 57 years; 174 men) were enrolled and stratified according to LFC quartiles. ACR (p<0.001) and MA prevalence (p=0.012) increased across the LFC quartiles. Multivariable logistic regression showed that the OR for MA (per SD increase in LFC) was 1.840 (95% CI 1.173 to 2.887, p=0.008) after adjustment for potential confounders including age, gender, waist-hip ratio, blood urea nitrogen, systolic and diastolic BP, fasting blood glucose, postprandial glucose, low-density lipoprotein-cholesterol, triglycerides, high-density lipoprotein-cholesterol, total cholesterol, estimated glomerular filtration rate and lipid-lowering drugs. The ROC analysis revealed that the optimal LFC cut-off value for predicting MA was 6.82%.ConclusionLFC is independently associated with MA in normotensive, euglycaemic middle-aged and elderly Chinese individuals. Screening for MA in people with NAFLD might facilitate early intervention to minimise kidney disease risk.

Download Full-text