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The article "Hepatobiliary effects and safety of tirzepatide: A systematic review and meta-analysis" published in Diabetes, Obesity & Metabolism explores the impact of tirzepatide on metabolic-dysfunction-associated steatotic liver disease (MASLD). The study found that tirzepatide treatment led to significant reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to placebo and insulin. Additionally, tirzepatide showed promising results in reducing liver fat content and had a comparable safety profile to other treatment options. The authors recommend further research with longer follow-up durations to better understand tirzepatide's potential as a therapeutic strategy for MASLD. [Extracted from the article]

Background Exercise and diet have positive effects on hepatic fat reduction, and protein supplementation is known to lower hepatic fat accumulation. However, the effect of a combination of exercise and whey protein supplementation (WPS) on hepatic fat content (HFC) is unknown. Methods We investigated the effect of WPS on HFC during resistance exercise and diet control intervention for four weeks. A total of 34 sedentary males participated and were randomly assigned to two groups: a protein supplement group (PSG, n = 18) and a control group (CG, n = 16). The PSG took 60 g of WPS per day, and the CG took 60 g of an isocaloric placebo per day. All participants were fed a calorie-controlled diet throughout the study period, with their daily caloric intake determined by their resting metabolic rate and physical activity level. Both groups performed resistance exercises supervised by experts at 60–70% of their maximum efforts for 60 min/day, 6 days/week for 4 weeks. HFC was assessed using the controlled attenuation parameter (CAP) after an 8 h fast, at pre-, mid-, and post-intervention. Liver enzymes and lipid profile were also analyzed after an 8 h fast and pre- and post-intervention. Results The CAP was significantly reduced after 4 weeks of intervention in both groups (PSG, p

Background: Specification of adipose tissues by whole-body magnetic resonance imaging (MRI) was performed and related to pulmonary function parameters in a population-based cohort. Methods: 203 study participants underwent whole-body MRI and pulmonary function tests as part of the KORA (Cooperative Health Research in the Augsburg Region) MRI study. Both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were derived from the T1-Dixon sequence, and hepatic adipose tissue from the proton density fat fraction (PDFFhepatic). Associations between adipose tissue parameters and spirometric indices such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and Tiffeneau-index (FEV1/FVC) were examined using multivariate linear regression analysis excluding cofounding effects of other clinical parameters. Results: VAT (β = −0.13, p = 0.03) and SAT (β = −0.26, p < 0.001), but not PDFFhepatic were inversely associated with FEV1, while VAT (β = −0.27, p < 0.001), SAT (β = −0.41, p < 0.001), and PDFFhepatic (β = −0.17, p = 0.002) were inversely associated with FVC. PDFFhepatic was directly associated with the Tiffeneau index (β = 2.46, p < 0.001). Conclusions: In the adjusted linear regression model, VAT was inversely associated with all measured spirometric parameters, while PDFFhepatic revealed the strongest association with the Tiffeneau index. Non-invasive adipose tissue quantification measurements might serve as novel biomarkers for respiratory impairment.

IntroductionMetabolic flexibility (MetF) is the capacity of an organism to oxidate substrate according to substrate availability or demand. The mismatch of substrate availability and oxidation may cause ectopic fat accumulation in the muscle and the liver. The objectives of the study are to examine the effect of 12 weeks of combined exercise on hepatic fat reduction and investigate metabolites related to MetF before and after the high-fat diet between individuals with NAFLD and healthy control with an active lifestyle.MethodsThis study is an open-label, single-center trial randomized controlled clinical study plus a cross-sectional comparison between individuals with NAFLD and healthy control. Individuals with NAFLD were allocated into two groups receiving resistance training (RT) combined with high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Anthropometric indicators, clinical blood markers about glucose, lipid metabolism, and hepatic fat content (HFC) were assessed before and after the intervention. The metabolomics was also used to investigate the discrepant metabolites and mechanisms related to MetF.DiscussionMetabolic flexibility reflects the capacity of an organism to switch the oxidation substrates flexibly, which is associated with ectopic fat accumulation. Our study aimed to explore the discrepant metabolites related to MetF before and after a high-fat diet between individuals with NAFLD and healthy control. In addition, the study also examined the effectiveness of RT combined with HIIT or MICT on hepatic fat reduction and quantificationally analyzed the metabolites related to MetF before and after the intervention. Our results provided a perspective on fatty liver-associated metabolic inactivity.Trial registrationClinicalTrials.gov: ChiCTR2200055110; Registered 31 December 2021, http://www.chictr.org.cn/index.aspx.

Introduction: Oligonol, an oligomerized-polyphenol from Litchi chinensis extract, has been shown to alleviate metabolic syndrome. The aim of this study was to evaluate the effects of oligonol in patients with nonalcoholic fatty liver disease (NAFLD). Methods: Adult patients with NAFLD defined by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) ≥11% were enrolled and then randomly assigned to receive either oligonol or placebo capsules. Primary endpoint was ≥30% reduction in MRI-PDFF at 24 weeks. Secondary outcomes were reductions in bodyweight, waist circumference, alanine transaminase, fasting blood sugar, and lipid profiles at week 24. Results: Forty patients were enrolled (n = 20/group). Primary endpoint was achieved in 20% in the oligonol group and 15% in the placebo group (p = 0.50). The authors found a reduction in MRI-PDFF between weeks 0 and 24 in the oligonol group; however, the change was not different from the placebo group. Secondary outcomes were similar between two groups. Discussion: Oligonol has not shown a significant therapeutic effect in NAFLD. Future studies with a longer duration of therapy might be needed to achieve the primary endpoint. Clinical Trial Registration Number: Thai Clinical Trial Registry identification number: TCTR20200814001. [ABSTRACT FROM AUTHOR]

Background: Specification of adipose tissues by whole-body magnetic resonance imaging (MRI) was performed and related to pulmonary function parameters in a population-based cohort. Methods: 203 study participants underwent whole-body MRI and pulmonary function tests as part of the KORA (Cooperative Health Research in the Augsburg Region) MRI study. Both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were derived from the T1-Dixon sequence, and hepatic adipose tissue from the proton density fat fraction (PDFFhepatic). Associations between adipose tissue parameters and spirometric indices such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and Tiffeneau-index (FEV1/FVC) were examined using multivariate linear regression analysis excluding cofounding effects of other clinical parameters. Results: VAT (β = −0.13, p = 0.03) and SAT (β = −0.26, p < 0.001), but not PDFFhepatic were inversely associated with FEV1, while VAT (β = −0.27, p < 0.001), SAT (β = −0.41, p < 0.001), and PDFFhepatic (β = −0.17, p = 0.002) were inversely associated with FVC. PDFFhepatic was directly associated with the Tiffeneau index (β = 2.46, p < 0.001). Conclusions: In the adjusted linear regression model, VAT was inversely associated with all measured spirometric parameters, while PDFFhepatic revealed the strongest association with the Tiffeneau index. Non-invasive adipose tissue quantification measurements might serve as novel biomarkers for respiratory impairment. [ABSTRACT FROM AUTHOR]

Featured Application: This study analyzes the suitability of the WB-EMS as a method to improve Hepatic Fat Content and Cardiometabolic Risk in Postmenopausal Women. This 10-week randomized controlled trial investigates the effects of two different training modalities on hepatic fat content and cardiometabolic risk in sedentary postmenopausal women. Besides, alterations in physical fitness, hepatic fat content, and cardiometabolic risk will be associated with changes in those blood parameters that are usually modifiable by exercise training. Postmenopausal women (N = 32; ~61 years) were randomly assigned to one of the following treatment groups; (1) based on international exercise recommendations (EX group; n = 16), (2) exercise plus whole-body electromyostimulation (EX+EMS group; n = 16). Cardiometabolic risk score was calculated based on the international diabetes federation's clinical criteria. Hepatic fat content was estimated using the fatty liver index. After the intervention, the cardiometabolic risk and the fatty liver index decreased, showing a higher impact on EX + WB-EMS. Physical fitness was assessed through aerobic and strength tests belonging to "Eurofit Testing Battery". In all of them, significant differences were observed (p < 0.001), though EX+ EMS experienced better improvements (p < 0.05). In conclusion, a 10-week exercise training program, especially with WB-EMS, triggered improvements in physical fitness and reduced cardiometabolic risk and hepatic fat content in sedentary postmenopausal women. [ABSTRACT FROM AUTHOR]

Genetic susceptibility to metabolic associated fatty liver disease (MAFLD) is complex and poorly characterized. Accurate characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk factors. We performed genome-wide association study (GWAS) on two noninvasive definitions of hepatic fat content: magnetic resonance imaging proton density fat fraction (MRI-PDFF) in 16,050 participants and fatty liver index (FLI) in 388,701 participants from the United Kingdom (UK) Biobank (UKBB). Heritability, genetic overlap, and similarity between hepatic fat content phenotypes were analyzed, and replicated in 10,398 participants from the University Medical Center Groningen (UMCG) Genetics Lifelines Initiative (UGLI). Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci, including two novel genomic loci harboring CREB3L1 (rs72910057-T, P = 5.40E-09) and GCM1 (rs1491489378-T, P = 3.16E-09), respectively, as well as three previously reported loci: PNPLA3, TM6SF2, and APOE. GWAS of FLI in UKBB identified 196 genome-wide significant loci, of which 49 were replicated in UGLI, with top signals in ZPR1 (P = 3.35E-13) and FTO (P = 2.11E-09). Statistically significant genetic correlation (rg) between MRI-PDFF (UKBB) and FLI (UGLI) GWAS results was found (rg = 0.5276, P = 1.45E-03). Novel MRI-PDFF genetic signals (CREB3L1 and GCM1) were replicated in the FLI GWAS. We identified two novel genes for MRI-PDFF and 49 replicable loci for FLI. Despite a difference in hepatic fat content assessment between MRI-PDFF and FLI, a substantial similar genetic architecture was found. FLI is identified as an easy and reliable approach to study hepatic fat content at the population level., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. highfat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration. [ABSTRACT FROM AUTHOR]

Aims: This study aims to evaluate and validate a simple quantitative ultrasound (US) method for determining the hepatic fat content (HFC) based on the combination of quantitative US hepatic/renal ratio (US-HRR) and quantitative US hepatic echo-intensity attenuation rate (US-HAR) as compared with [1H]-magnetic resonance spectroscopy (1H-MRS).Material and Methods: There were a total of 242 subjects recruited in the present study. All subjects were examined for HFC by quantitative US and 1H-MRS methods. The QUS-HRR and QUS-HAR were calculated from ordinary ultrasound images of liver and kidney with a triple modality 3D abdominal phantom using the Image J software.Results: The results found that US-HRR and US-HAR correlated with 1H-MRS HFC (US-HRR: r=0.946, p<0.001; US-HAR: r=0.936, p<0.001). The equation for HFC prediction by using quantitative US was: HFC (%) = 28.965 × US-HRR + 218.045 × US-HAR - 8.892. Subgroup analysis in study subjects with body mass index (BMI) ≥28 showed that quantitative US HFC was associated with 1H-MRS HFC (R2=0.953, p<0.001). Receiver operating characteristic (ROC) analysis observed that the cut-off value of fatty liver diagnosis was 6.71% in using the quantitative US model; the sensitivity and specificity for fatty liver diagnosis were 94.15% and 96.30%, respectively. Variability analysis indicated that there was a relative high degree of consistency in the measurement of HFC with different operators or ultrasonic apparatus.Conclusions: Quantitative US measurement could be regarded as a simple, sensitive tool to accurately assess HFC. It provides a valid alternative to 1H-MRS as an easy, non-invasive option for the precise estimation of HFC in clinical practice. [ABSTRACT FROM AUTHOR]

Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. Resultant fatty liver disease (FLD) variably progresses to steatohepatitis, cirrhosis and hepatocellular carcinoma (HCC).1 Evidence for shared determinants of FLD and end-stage liver complications first arose from human genetics,2 showing that the main risk variants for FLD had a proportional impact on fibrosis and HCC, and fibrosis/HCC development was very closely linked to the impact on the lipid content of hepatocytes.3,4 However, this theory is challenged by the observation that hepatic fat accumulation and biochemical markers of liver damage and inflammation tend to decrease with the progression of liver fibrosis.5-7 Interpretation of these observational studies is challenging, as they tend to be cross-sectional in nature and often include participants that already have cirrhosis.8 In patients affected by FLD, hepatic fat content is progressively reduced (even to within the normal range) in individuals with the most advanced liver disease,9 defining the concept of "burnt-out nonalcoholic steatohepatitis". Keywords: diabetes; cirrhosis; FOXO1; hepatic fat content; NASH EN diabetes cirrhosis FOXO1 hepatic fat content NASH 2816 2818 3 12/24/21 20211201 NES 211201 Environmental stressors such as obesity and insulin resistance, exposure to hepatotoxins, and hepatitis C virus infection increase hepatocyte lipid content, with a significant change in triglyceride, cholesterol as well as other lipid species. [Extracted from the article]

This 10-week randomized controlled trial investigates the effects of two different training modalities on hepatic fat content and cardiometabolic risk in sedentary postmenopausal women. Besides, alterations in physical fitness, hepatic fat content, and cardiometabolic risk will be associated with changes in those blood parameters that are usually modifiable by exercise training. Postmenopausal women (N = 32; ~61 years) were randomly assigned to one of the following treatment groups; (1) based on international exercise recommendations (EX group; n = 16), (2) exercise plus whole-body electromyostimulation (EX+EMS group; n = 16). Cardiometabolic risk score was calculated based on the international diabetes federation’s clinical criteria. Hepatic fat content was estimated using the fatty liver index. After the intervention, the cardiometabolic risk and the fatty liver index decreased, showing a higher impact on EX + WB-EMS. Physical fitness was assessed through aerobic and strength tests belonging to “Eurofit Testing Battery”. In all of them, significant differences were observed (p < 0.001), though EX+ EMS experienced better improvements (p < 0.05). In conclusion, a 10-week exercise training program, especially with WB-EMS, triggered improvements in physical fitness and reduced cardiometabolic risk and hepatic fat content in sedentary postmenopausal women.

Weight loss by lifestyle modification is the cornerstone therapy of Non Alcoholic Fatty Liver Disease. Low carbohydrate diet has showed favorable effects for body weight as well as hepatic fat content in several reports. In this meta-analysis, we review clinical studies article to date regarding the composition of the diet and analyzed the impact of low carbohydrate diet comparing to low calorie diet on hepatic fat change, AST and ALT using Forest plot. We aimed to investigate the efficacy of low carbohydrate diet on NAFLD. We collected studies that were conducted with various amounts of carbohydrate and different methods for changing the hepatic fat and fibrosis. Eleven clinical studies (seven randomized controlled trials) were selected on the efficacy and safety of low carbohydrate diet on NAFLD patients. Four studies evaluated hepatic fat by magnetic resonance imaging and two evaluated hepatic fat using computed tomography. However, the pools of subjects were small, the criterion for low carbohydrate was variable, and there is yet an established standard method of evaluation of liver. In meta-analysis, there was no significant difference between low carbohydrate diet group and low fat diet group on the improvement of hepatic fat content and transaminases in NAFLD. So far there's little evidence that low-carbohydrate diet has more beneficial effect on NAFLD than low calorie diet in similar calorie intake. [ABSTRACT FROM AUTHOR]

• A Mediterranean and low carbohydrate diet decreases hepatic fat more than a low-fat diet, beyond visceral fat changes. • Decreases in hepatic fat are independently associated with specific improved parameters. • The beneficial effect of a Mediterranean diet over a low-fat diet is mainly mediated by decreases in hepatic fat. It is unclear if a reduction in hepatic fat content (HFC) is a major mediator of the cardiometabolic benefit of lifestyle intervention, and whether it has prognostic significance beyond the loss of visceral adipose tissue (VAT). In the present sub-study, we hypothesized that HFC loss in response to dietary interventions induces specific beneficial effects independently of VAT changes. In an 18-month weight-loss trial, 278 participants with abdominal obesity/dyslipidemia were randomized to low-fat (LF) or Mediterranean/low-carbohydrate (MED/LC + 28 g walnuts/day) diets with/without moderate physical activity. HFC and abdominal fat-depots were measured using magnetic resonance imaging at baseline, after 6 (sub-study, n = 158) and 18 months. Of 278 participants (mean HFC 10.2% [range: 0.01%–50.4%]), the retention rate was 86.3%. The %HFC substantially decreased after 6 months (−6.6% absolute units [−41% relatively]) and 18 months (−4.0% absolute units [−29% relatively]; p <0.001 vs. baseline). Reductions of HFC were associated with decreases in VAT beyond weight loss. After controlling for VAT loss, decreased %HFC remained independently associated with reductions in serum gamma glutamyltransferase and alanine aminotransferase, circulating chemerin, and glycated hemoglobin (p <0.05). While the reduction in HFC was similar between physical activity groups, MED/LC induced a greater %HFC decrease (p = 0.036) and greater improvements in cardiometabolic risk parameters (p <0.05) than the LF diet, even after controlling for VAT changes. Yet, the greater improvements in cardiometabolic risk parameters induced by MED/LC were all markedly attenuated when controlling for HFC changes. %HFC is substantially reduced by diet-induced moderate weight loss and is more effectively reduced by the MED/LC diet than the LF diet, independently of VAT changes. The beneficial effects of the MED/LC diet on specific cardiometabolic parameters appear to be mediated more by decreases in %HFC than VAT loss. High hepatic fat content is associated with metabolic syndrome, type 2 diabetes mellitus, and coronary heart disease. In the CENTRAL 18-month intervention trial, a Mediterranean/low-carbohydrate diet induced a greater decrease in hepatic fat content than a low-fat diet, conferring beneficial health effects that were beyond the favorable effects of visceral fat loss. ClinicalTrials.gov Identifier: NCT01530724. [ABSTRACT FROM AUTHOR]

Background Diets rich in fat and added sugars (especially fructose) play an important role in the pathogenesis of nonalcoholic liver disease (NAFLD), but there is only limited information on the acute effects of these nutrients on hepatic fat content (HFC). Objectives We therefore explored how the administration of high-fat load, glucose, fructose, and combinations thereof affects HFC measured in vivo using proton magnetic resonance spectroscopy (1H-MRS) in healthy subjects. Methods Ten healthy nonsteatotic male volunteers (age 38.5 ± 9.6 y, body mass index [BMI, kg/m2] 26.9 ± 2.7) underwent, in random order, 6 experiments, each lasting 8 h, that included: 1) fasting; 2) a high-fat load (150 g of fat [dairy cream] at time 0); 3) glucose (3 doses of 50 g at 0, 2, and 4 h); 4) a high-fat load with glucose; 5) fructose (3 doses of 50 g at 0, 2, and 4 h); and 6) a high-fat load with fructose. HFC was measured using 1H-MRS prior to test meal administration (before time 0) and at 3 and 6 h. Plasma concentrations of triglycerides, nonesterified fatty acids, glucose, and insulin were monitored throughout each experiment. Results HFC increased to 119 ± 19% (P  < 0.05) and 117 ± 17% (P  < 0.01) of baseline when subjects consumed a high-fat load alone or a high-fat load with fructose, respectively, but was not affected when glucose was coadministered with a high-fat load. HFC was not affected when subjects had fasted or had consumed repeated doses of fructose. When subjects were administered 3 doses of glucose, HFC dropped to 85 ± 13% (P  < 0.05) of baseline. Conclusions Our results demonstrate that fructose and glucose have a different immediate impact on HFC in humans in vivo. Clinical trial registry: The study was registered at clinicaltrials.gov and obtained clinicaltrials.gov identifier: NCT03680248. [ABSTRACT FROM AUTHOR]

The present study investigated the association of carbohydrate intake and isocaloric substitution with different types of fat with visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat content as determined by magnetic resonance imaging (MRI). Data from 283 participants (mean age 56.1 ± 9.0 years) from the MRI sub study of the KORA FF4 study were included. VAT, SAT and total body fat were quantified by a volume-interpolated VIBE-T1w-Dixon MR sequence. Hepatic fat content was determined as the proton density fat-fraction (PDFF) derived from multiecho-T1w MR sequence. Dietary intake was estimated using information provided by two different instruments, that is, repeated 24-h food lists and a food frequency questionnaire. Replacing total carbohydrates with an isoenergetic amount of total fat was significantly positively associated with VAT and hepatic fat, while there was no significant association with SAT. The multivariable adjusted β-coefficient for replacing 5% of total energy (5E%) carbohydrates with total fat was 0.42 L (95% CI: 0.04, 0.79) for VAT. A substitution in total fat intake by 5E% was associated with a significant increase in liver fat content by 23% (p-value 0.004). If reproduced in prospective studies, such findings would strongly argue for limiting dietary fat intake. [ABSTRACT FROM AUTHOR]

Abstract Aim Type 2 diabetes (T2D) alters glucagon, glucagon-like peptide (GLP)-1, glucose-dependent insulinotropic polypeptide (GIP) and hepatic energy metabolism, yet the possible relationships remain unclear. Methods In this observational study, lean insulin-sensitive control subjects (BMI: 23.2 ± 1.5 kg/m2), age-matched insulin-resistant obese subjects (BMI: 34.3 ± 1.7 kg/m2) and similarly obese elderly T2D patients (BMI: 32.0 ± 2.4 kg/m2) underwent mixed-meal tolerance tests (MMTTs), and assessment of hepatic γATP, inorganic phosphate (P i) and lipids using 31P/1H magnetic resonance spectroscopy. Meal-induced secretion of glucagon and incretins was calculated from incremental areas under the concentration–time curves (iAUCs). Peripheral and adipose tissue insulin sensitivity were assessed from time courses of circulating glucose, insulin and free fatty acids. Results MMTT-derived peripheral insulin sensitivity was lowest in T2D patients (P < 0.001), while glucagon concentrations were comparable across all three groups. At 260 min, GLP-1 was lower in T2D patients than in controls, whereas GIP was lowest in obese individuals. Fasting glucagon concentrations correlated positively with fasting (r = 0.60) and postprandial hepatocellular lipid levels (160 min: r = 0.51, 240 min: r = 0.59), and negatively with adipose tissue insulin sensitivity (r = −0.73). Higher meal-induced glucagon release (iAUC 0–260 min) correlated with lower fasting (r = −0.62) and postprandial P i levels (160 min: r = −0.43, 240 min: r = −0.42; all P < 0.05). Higher meal-induced release of GIP (iAUC 0–260 min) correlated positively with fasting (r = 0.54) and postprandial serum triglyceride concentrations (iAUC 0–260 min , r = 0.54; all P < 0.01). Conclusion Correlations between fasting glucagon and hepatic lipids and between meal-induced glucagon and hepatic P i suggest a role for glucagon in hepatic energy metabolism. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common non-cutaneous malignancy and the second leading cause of cancer mortality in the United States. Breast cancer is a heterogeneous disease; diagnosis at an early stage renders it potentially curable, whereas advanced metastatic disease carries a worse prognosis., Objectives: To investigate whether hepatic steatosis (HS) is associated with liver metastases in patients with newly diagnosed stage IV female breast cancer patients (either de novo metastatic breast cancer or recurrent metastatic breast cancer) using non-contrast computed tomography (CT) as a marker of HS., Design: Retrospective analysis., Methods: We retrospectively identified 168 patients with stage IV breast cancer with suitable imaging from a prospectively maintained oncologic database. Three radiologists manually defined hepatic regions of interest on non-contrast CT images, and attenuation data were extracted. HS was defined as a mean attenuation <48 Hounsfield units. The frequency of hepatic metastatic disease was calculated for patient with and without HS. Relationships between HS and various patient (age, body mass index, race) and tumor (hormone receptor status, HER2 status, tumor grade) characteristics were also analyzed., Results: There were 4 patients with liver metastasis in the HS group (41 patients) versus 20 patients with liver metastases in the non-HS group (127 patients). The difference in frequencies of liver metastases among patients with (9.8%) versus without (15.7%) hepatic steatosis (odds ratio = 1.72 [0.53-7.39]) was not statistically significant ( P  = .45). Body mass index was significantly higher ( P  = .01) among patients with hepatic steatosis (32.2 ± 7.3 vs 28.8 ± 7.1 kg/m 2 ). Otherwise, there were no significant differences between patients with versus without HS with respect to regarding age, race, hormone receptor status, HER2 status, or tumor grade., Conclusion: The frequency of hepatic metastatic disease in patients with stage IV breast cancer is similar for steatotic and non-steatotic livers., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: High serum Retinol Binding Protein 4 (RBP4) levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured serum RBP4 and hepatic fat content (HFC), visceral (VFA) and subcutaneous abdominal fat area (SFA) in 106 subjects with non-alcoholic fatty liver disease (NAFLD) without known diabetes. Methods: 106 patients with NAFLD (M/F: 61/45, aged 47.44 ± 14.16 years) were enrolled. Subjects with known diabetes, chronic virus hepatitis, and those with alcohol consumption ≥30 g/d in man and ≥20 g/d in woman were excluded. Anthropometrics and laboratory tests, including lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (γ-GT) were conducted. HFC, VFA and SFA were determined by CT scan. Serum RBP4 was detected by an enzyme immunoassay kit and validated by quantitative Western blotting. Results: Circulating RBP4 was negatively associated with high-density lipoprotein cholesterol (HDL-c) (r = -0.392, p < 0.001), but positively with waist-to-hip ratio (WHR) (r = 0.343, p = 0.001), triglyceride (r = 0.330, p = 0.002), VFA (r = 0.298, p = 0.027), systolic blood pressure (r = 0.247, p = 0.020), diastolic blood pressure (r = 0.241, p = 0.023), γ-GT (r = 0.239, p = 0.034), waist circumference (r = 0.218, p = 0.040). Differently, serum RBP4 levels were not associated with HFC (r = 0.199, p = 0.071), SFA, age, BMI, total cholesterol, low-density lipoprotein cholesterol (LDL-c), ALT or AST (all p > 0.05). Multiple linear regression analysis revealed that RBP4 correlated independently with VFA (Standard β = 0.357, p = 0.019) and HDL-c (Standard β = -0.345, p = 0.023) in all subjects, HDL-c (Standard β = -0.315, p = 0.040) in men, VFA/SFA in women (Standard β = 0.471, p = 0.049), not with HFC. However, serum RBP4 was positively correlated with HFC when HFC below 6.34% (r = 0.574, p = 0.001). Conclusions: RBP4 could be a marker of abdominal obesity, however, the role of RBP4 in the pathogenesis of NAFLD is not sufficiently elucidated. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of the study was to compare the effect of six (A6 regimen) vs two meals a day, breakfast and lunch (B2 regimen), on body weight, hepatic fat content (HFC), insulin resistance and beta cell function. Methods: In a randomised, open, crossover, single-centre study (conducted in Prague, Czech Republic), we assigned 54 patients with type 2 diabetes treated with oral hypoglycaemic agents, both men and women, age 30-70 years, BMI 27-50 kg/m and HbA 6-11.8% (42-105 mmol/mol), to follow two regimens of a hypoenergetic diet, A6 and B2, each for 12 weeks. Randomisation and allocation to trial groups ( n = 27 and n = 27) were carried out by a central computer system. Individual calculations of energy requirements for both regimens were based on the formula: (resting energy expenditure × 1.5) − 2,092 kJ. The diet in both regimens had the same macronutrient and energy content. HFC was measured by proton magnetic resonance spectroscopy. Insulin sensitivity was measured by isoglycaemic-hyperinsulinaemic clamp and calculated by mathematical modelling as oral glucose insulin sensitivity (OGIS). Beta cell function was assessed during standard meal tests by C-peptide deconvolution and was quantified with a mathematical model. For statistical analysis, 2 × 2 crossover ANOVA was used. Results: The intention-to-treat analysis included all participants ( n = 54). Body weight decreased in both regimens ( p < 0.001), more for B2 (−2.3 kg; 95% CI −2.7, −2.0 kg for A6 vs −3.7 kg; 95% CI −4.1, −3.4 kg for B2; p < 0.001). HFC decreased in response to both regimens ( p < 0.001), more for B2 (−0.03%; 95% CI −0.033%, −0.027% for A6 vs −0.04%; 95% CI −0.041%, −0.035% for B2; p = 0.009). Fasting plasma glucose and C-peptide levels decreased in both regimens ( p < 0.001), more for B2 ( p = 0.004 and p = 0.04, respectively). Fasting plasma glucagon decreased with the B2 regimen ( p < 0.001), whereas it increased ( p = 0.04) for the A6 regimen ( p < 0.001). OGIS increased in both regimens ( p < 0.01), more for B2 ( p = 0.01). No adverse events were observed for either regimen. Conclusions/interpretation: Eating only breakfast and lunch reduced body weight, HFC, fasting plasma glucose, C-peptide and glucagon, and increased OGIS, more than the same caloric restriction split into six meals. These results suggest that, for type 2 diabetic patients on a hypoenergetic diet, eating larger breakfasts and lunches may be more beneficial than six smaller meals during the day. Trial registration ClinicalTrials.gov number, NCT01277471, completed. Funding Grant NT/11238-4 from Ministry of Health, Prague, Czech Republic and the Agency of Charles University - GAUK No 702312. [ABSTRACT FROM AUTHOR]

Background: Early quantitative assessment of liver fat content is essential for patients with fatty liver disease. Mounting evidence has shown that magnetic resonance (MR) technique has high accuracy in the quantitative analysis of fatty liver, and is suitable for monitoring the therapeutic effect on fatty liver. However, many packaging methods and postprocessing functions have puzzled radiologists in clinical applications. Therefore, selecting a quantitative MR imaging technique for patients with fatty liver disease remains challenging., Aim: To provide information for the proper selection of commonly used quantitative MR techniques to quantify fatty liver., Methods: We completed a systematic literature review of quantitative MR techniques for detecting fatty liver, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. Studies were retrieved from PubMed, Embase, and Cochrane Library databases, and their quality was assessed using the Quality Assessment of Diagnostic Studies criteria. The Reference Citation Analysis database (https:// www.referencecitationanalysis.com) was used to analyze citation of articles which were included in this review., Results: Forty studies were included for spectroscopy, two-point Dixon imaging, and multiple-point Dixon imaging comparing liver biopsy to other imaging methods. The advantages and disadvantages of each of the three techniques and their clinical diagnostic performances were analyzed., Conclusion: The proton density fat fraction derived from multiple-point Dixon imaging is a noninvasive method for accurate quantitative measurement of hepatic fat content in the diagnosis and monitoring of fatty liver progression., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

OBJECTIVES:: To study the effect of pioglitazone (PIO) on plasma resistin concentration, endogenous glucose production (EGP), and hepatic fat content (HFC) in patients with type II diabetes (T2DM). SUBJECTS:: A total of 13 T2DM patients (age=51±2?y, BMI=29.7±1.1?kg/m2, HbA1c=8.0±0.5%). METHODS:: HFC (magnetic resonance spectroscopy) and basal plasma resistin concentration were quantitated before and after PIO treatment (45?mg/day) for 16 weeks. Subjects received a 3?h euglycemic insulin (100?mU/m2/min) clamp with 3-[3H] glucose to determine rates of EGP and tissue glucose disappearance (Rd) before and after PIO. RESULTS:: PIO reduced fasting plasma glucose (10.3±0.7 to 7.6±0.6?mmol/l, P<0.001) and HbA1c (8.0±0.4 to 6.8±0.3%, P<0.001) despite increased body weight (83.2±3.4 to 86.3±3.4?kg, P<0.001). PIO improved Rd (4.9±0.4 to 6.6±0.5?mg/kg/min, P<0.005) and reduced EGP (0.22±0.04 to 0.06±0.02?mg/kg/min, P<0.01) during the insulin clamp. Following PIO, HFC decreased from 21.1±3.5 to 11.2±2.1% (P<0.005), and plasma resistin decreased from 5.3±0.6 to 3.5±0.3?ng/ml (P<0.01). Plasma resistin concentration correlated positively with HFC before (r=0.58, P<0.05) and after (r=0.55, P<0.05) PIO treatment. Taken collectively, plasma resistin concentration, before and after PIO treatment, correlated positively with hepatic fat content (r=0.66, P<0.001) and EGP during the insulin clamp (r=0.41, P<0.05). However, the plasma resistin concentration did not correlate with whole body glucose disposal (Rd) during the insulin clamp either before (r=-0.18, P=NS) or after (r=-0.13, P=NS) PIO treatment. CONCLUSIONS:: PIO treatment in T2DM causes a significant decrease in plasma resistin concentration. The decrease in plasma resistin is positively correlated with the decrease in hepatic fat content and improvement in hepatic insulin sensitivity.International Journal of Obesity (2004) 28, 783-789. doi:10.1038/sj.ijo.0802625 Published online 16 March 2004 [ABSTRACT FROM AUTHOR]

• Adiposity influenced increased hepatic fat content (HFC), a hallmark of NAFLD • EWAS identified 4 QTLs that can increase HFC, including a novel SNP rs4788084. • IL27 regulates inflammation and rs4788084 affects IL27 expression in liver,. • SNPs in PNPLA3-SAMM50 genes affected both HFC and NAFLD severity among Indians. • Across varied obesity status, rs738409-G and rs4788084-A carriers had higher HFC. Non-alcoholic fatty liver disease (NAFLD) is a global epidemic that often progresses to liver cirrhosis and hepatocellular carcinoma. In contrast to most world populations where NAFLD is mostly prevalent among obese, NAFLD among Indians and generally among South and South-East Asians is unique and highly prevalent among individuals who are lean. Genetics of NAFLD in Indian populations is understudied. In this study, we have used an exome-wide approach to identify genetic determinants of hepatic fat content (HFC) in India. HFC was measured in 244 participants using Proton magnetic resonance spectroscopy (H1-MRS). Quantitative trait loci (QTL) mapping was done exome-wide, to identify SNPs associated with HFC. The effects of the interaction between adiposity and QTLs on HFC were studied using a regression model. Association of the significant loci with disease severity was studied in 146 NAFLD patients among 244 participants, who underwent liver biopsy. Our study identified 4 significantly associated SNPs (rs738409 and rs2281135 (PNPLA3), rs3761472 (SAMM50), rs17513722 (FAM161A) and rs4788084), with HFC after adjusting for the effects of covariates (p-value < 0.0005). rs738409, rs2281135 (PNPLA3), and rs3761472 (SAMM50) were associated with hepatocyte ballooning, lobular and portal inflammation and non-alcoholic steatohepatitis (NASH) (p-value < 0.05). rs4788048 is an eQTL for IL27 and SULT1A2 genes, both of which are highly expressed in healthy livers and are likely to be involved in NAFLD pathogenesis. Our study identified the novel association of rs4788084 with HFC, which regulates the expression of IL-27, an immune regulatory gene. We further showed that adiposity affected the HFC, irrespective of the genetic predisposition. [ABSTRACT FROM AUTHOR]