Hepatic Fat Content Research Articles

Circulating Levels of microRNA-122 and Hepatic Fat Change in Response to Weight-Loss Interventions: CENTRAL Trial.

Little is known about the relations between changes in circulating microRNA-122 (miR-122) and liver fat in response to weight-loss interventions. We aimed to investigate the association between miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. The CENTRAL trial is an 18-month randomized, controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat diet or a Mediterranean/low-carbohydrate diet. After 6 months of dietary intervention, each diet group was further randomized into added physical activity groups or no added physical activity groups for the following 12 months of intervention. The current study included 220 participants at baseline and 134 participants with repeated measurements on serum miR-122 and hepatic fat content over 18 months. Serum miR-122 significantly increased from baseline to 18 months, while no difference was observed across the 4 intervention groups. We found a significant association between miR-122 and hepatic fat content at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content (P < 0.001). Furthermore, we found that higher elevations in miR-122 were associated with less reductions in hepatic fat percentage during 18-month interventions (β = 1.56, P = 0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months (P interaction = 0.02). Our data indicate that participants with higher elevation in serum miR-122 may benefit less in reduction of hepatic fat content in response to diet and physical activity interventions.

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

BackgroundLipocalin-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).MethodsThis 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.ResultsAmong 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.ConclusionsSerum LCN2 levels are related to obesity and NAFLD. The decreased serum LCN2 levels could be an indicator of hepatic steatosis improvement.

Hepatic venous diameter and liver volume index reflects extent of hepatic steatosis; a population-based study from healthy liver donors

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease in recent years. Further, steatosis is a common finding encountered in living related liver transplant donors (LDLT) during their presurgical evaluation. We have observed that increased liver fat content in donors was associated with relatively smaller hepatic venous diameters. This study was designed to evaluate whether there is a correlation between hepatic venous diameter and liver fat content and whether this would result in a predictive index for hepatic steatosis based on diameters, and liver volume.

Fasting, Nutrition and Weight Loss: An Approach to Refine Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is considered as one of the most common causes of chronic liver disease. It includes a group of conditions associated with fat deposition in liver cells. Also, NAFLD is strongly associated with obesity and insulin resistance (IR). Until now, there is no pharmacological treatment validated for this disease. Fasting, nutritional intervention, and weight loss can be considered the first line in treating hepatic steatosis. This review is based on the scientific evidence showing the results of these interventions in the past years. The results include fasting and nutritional support for NAFLD treatment in humans. In clinical trials and cohort studies, an increase in hepatic fat content was correlated with a weight loss of at least 7% and a diet resembling the Mediterranean diet (MD) improving hepatic biomarkers and histological regression of NAFLD. Fasting is a dietary approach known to improve the lipid profile in healthy and obese populations by decreasing overall cholesterol, triglycerides, LDL, and increasing HDL. Bariatric surgery helps improve liver fat content in patients with serious health problems due to overweight.

Current status and challenges in the drug treatment for fibrotic nonalcoholic steatohepatitis.

Currently, nonalcoholic steatohepatitis (NASH) is one of the most common forms of chronic hepatitis, increasing the burden of health care worldwide. In patients with NASH, the fibrosis stage is the most predictive factor of long-term events. However, there are still no drugs approved by the Food and Drug Administration of the United States for treating biopsy-proven NASH with fibrosis or cirrhosis. Although some novel drugs have shown promise in preclinical studies and led to improvement in terms of hepatic fat content and steatohepatitis, a considerable proportion of them have failed to achieve histological endpoints of fibrosis improvement. Due to the large number of NASH patients and adverse clinical outcomes, the search for novel drugs is necessary. In this review, we discuss current definitions for the evaluation of treatment efficacy in fibrosis improvement for NASH patients, and we summarize novel agents in the pipeline from different mechanisms and phases of trial. We also critically review the challenges we face in the development of novel agents for fibrotic NASH and NASH cirrhosis.

Abstract 8879: Circulating Levels of MicroRNA-122 and Hepatic Fat Changes in Response to Lifestyle Intervention: Central Magnetic Resonance Imaging Randomized Controlled Trial

Introduction: Compelling evidence has linked liver-specific microRNA-122 (miR-122) expression with hepatic fat distribution; however, little is known about the relations between changes in circulating miR-122 and liver fat in response to weight-loss interventions. We aimed to prospectively investigate the association between serum miR-122 and changes of hepatic fat content during 18-month diet and physical activity interventions. Methods: The CENTRAL trial is an 18-month randomized controlled trial among adults with abdominal obesity or dyslipidemia. Subjects were randomly assigned to a low-fat (LF) diet or a Mediterranean/low-carbohydrate (MED/LC) diet. After six months of dietary intervention, each diet group was further randomized into added physical activity groups (LFPA+, MED/LCPA+) or no added physical activity groups (LFPA-, MED/LCPA-) for the following 12 months of intervention. The current study included 220 participants with repeated measurements on serum miR-122 and hepatic fat content (percentage) over 18 months. Results: In the study participants, serum concentration of miR-122 significantly increased from baseline to 18 months, while no difference was observed across the four intervention groups. We found a significant association between miR-122 and hepatic fat percentage at baseline, as per unit increment in log-transformed miR-122 was associated with 3.79 higher hepatic fat content ( P trend&lt;0.001). In addition, we found that a higher elevation in log-transformed miR-122 was associated with a greater reduction in hepatic fat percentage during 18-month interventions, independent of weight loss (β=1.56, P trend=0.002). We also found a significant interaction between changes in miR-122 and baseline fasting plasma glucose with hepatic fat content changes in 18 months ( P interaction=0.02). The association between changes in miR-122 and hepatic fat content changes appeared to be stronger among participants with higher baseline fasting glucose levels than those with lower levels. Conclusion: Our data indicate that participants with higher serum miR-122 levels may benefit more in reduction of hepatic fat content in response to Mediterranean/low-carbohydrate diet and physical activity interventions.

Abstract 12815: Changes in Circulating microRNA-375 Levels in Response to Lifestyle Interventions and Improvements in Visceral Adiposity and Hepatic Fat Content: The CENTRAL Trial

Introduction: MicroRNA (miRNAs) are short non-coding RNAs that regulate gene expression at the translational level. Circulating exosomal miRNAs have emerged as novel biomarkers of obesity, insulin resistance, and related metabolic abnormalities. miR-375 has been identified as a regulator of insulin secretion, and miR-375 may also be involved in regulating visceral adiposity and ectopic fat accumulation in the liver. Hypothesis: We aimed to investigate whether changes in circulating miR-375 induced by lifestyle interventions were related to improved visceral adiposity and hepatic fat depot among individuals with abdominal obesity. Methods: This study included adults with abdominal obesity from an 18-month diet and physical activity intervention study (the CENTRAL trial) and with available data on circulating miR-375-3p at baseline (n=222) and 18 months (n=152). Magnetic resonance imaging (MRI) was performed to assess body fat distribution and ectopic fat depots. Outcome measurements included 18-month changes in abdominal (total [TAT], visceral [VAT], deep subcutaneous [DSAT], superficial subcutaneous [SSAT]) adipose tissue area and intrahepatic fat content. Results: At baseline, higher levels of miR-375 were related to lower degrees of BMI ( p =0.0006), waist circumference ( p =0.0008), as well as abdominal adipose tissue area (TAT [ p =0.0024], VAT [ p =0.059], DSAT [ p =0.011], and SSAT [ p =0.0027]). There was a significant increase in circulating miR-375 levels after the 18-month lifestyle interventions ( P by paired t-test &lt; 0.0001). When we analyzed effects (β) of per 1 SD increase in miR-375 changes on the outcomes after adjusting for covariates including baseline levels of miR-375 and BMI, we found that greater increase in miR-375 was associated with larger reductions of VAT (β -8.09 [3.09] cm 2 , p =0.01), as well as DSAT (β -7.87 [2.21] cm 2 , p =0.001) and intrahepatic fat content (β -1.38% [0.5%], p =0.006) at 18 months. Conclusions: Circulating miR-375 levels significantly increased after the long-term lifestyle interventions, and greater increases in miR-375 were related to significant improvements in visceral adiposity and liver fat content that are closely related to insulin resistance in adults with abdominal obesity.

Effects of Metformin on Hepatic Steatosis in Adults with Nonalcoholic Fatty Liver Disease and Diabetes: Insights from the Cellular to Patient Levels.

Nonalcoholic fatty liver disease (NAFLD) patients with diabetes constitute a subgroup of patients with a high rate of liver-related complications. Currently, there are no specific drug recommendations for these patients. Metformin, a conventional insulin sensitizer agent, has been widely prescribed in patients with diabetes. Metformin treatment has been shown to be effective at alleviating hepatic lipogenesis in animal models of NAFLD, with a variety of mechanisms being deemed responsible. To date, most studies have enrolled diabetic patients who are treated with metformin, with the drug being taken continuously throughout the study. Although evidence exists regarding the benefits of metformin for NAFLD in preclinical studies, reports on the efficacy of metformin in adult NAFLD patients have had some discrepancies regarding changes in liver biochemistry and hepatic fat content. Evidence has also suggested possible effects of metformin as regards the prevention of hepatocellular carcinoma tumorigenesis. This review was performed to comprehensively summarize the available in vitro, in vivo and clinical studies regarding the effects of metformin on liver steatosis for the treatment of adult NAFLD patients with diabetes. Consistent reports as well as controversial findings are included in this review, and the mechanistic insights are also provided. In addition, this review focuses on the efficacy of metformin as a monotherapy and as a combined therapy with other antidiabetic medications.

Exercise dose on hepatic fat and cardiovascular health in adolescents with excess of adiposity.

The HEPAFIT study was aimed at examining the impact of a 6-month physical education intervention, considering various levels of exercise intensity, on hepatic fat and cardiometabolic health outcomes in adolescents with excess adiposity. Adolescents (n=120), 11-17 years with excess adiposity by body fat >30%, were randomly assigned to one of the following 4 groups for 6months: (1) standard physical education lessons, control (CTRL); (2) high-intensity physical education (HIPE); (3) low-to-moderate intensity physical education (LIPE) and (4) combined HIPE and LIPE (PLUS). The primary outcome was hepatic fat content measured by vibration-controlled transient elastography (controlled attenuation parameter [CAP]). Secondary outcomes were traditional cardiovascular health markers (body composition, serum lipids, aminotransferases and health-related physical fitness components). Adjusted mixed effects linear models revealed a significant decrease in CAP levels in HIPE (-20.02 dB/m, p<0.0001) (p=0.001 vs. CTRL group) and PLUS (-16.25 dB/m, p=0.005) groups. Body fat decreased in the HIPE (-2.88%, p < 0.001) (p=0.001 vs. CTRL group) and LIPE (-1.26%, p=0.022) groups. The physical fitness components were increased in the HIPE and PLUS group relative to the baseline (p < 0.05), and the HIPE group showed a reduction in the total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels (p < 0.05). Implementation of a 6-month physical education exercise program, particularly high-intensity or combined high and low-intensity, improves hepatic fat storage and significantly reduces cardiometabolic markers in adolescents with excess of adiposity. Interventions involving supervised physical exercise may help to improve metabolism and fat deposition at the hepatic level, thus preventing the development of non-alcoholic fatty liver disease in adolescents.

Dietary Pennisetum sinese Roxb meal reduces lipid accumulation and alleviates enteritis in juvenile grass carp, Ctenopharyngodon idella

Grass carp (Ctenopharyngodon idella) rarely consume grass-type feedstuffs in the commercial aquaculture industry. In this study, the effects of dietary Pennisetum sinese Roxb meal (PSRM) on the growth, lipid accumulation, and intestinal health of juvenile grass carp were explored. Six practical isonitrogenous (crude protein, 28.61%) and isocaloric (gross energy, 14.69 kJ g–1) diets with increasing PSRM contents (0.0%, 5.0%, 10.0%, 15.0%, 20.0%, and 25.0%; at the expense of soybean meal, wheat meal, and soybean oil) were formulated to feed juvenile grass carp for eight weeks. Fish fed 5–25% PSRM showed significantly increased growth and decreased feed conversion ratios compared with fish fed the control diet; fish that were fed 5% PSRM showed the best growth and feed efficiency. Diets supplemented with 5–25% PSRM significantly reduced lipid accumulation in the hepatocytes of grass carp, as indicated by the suppression of the hepatopancreas index, hepatic crude fat content and lipid droplet distribution, and hepatic triglyceride and free fatty acid (FFA) contents. Dietary PSRM also significantly decreased the lipid content in the adipose tissue by reducing the intraperitoneal fat index (5–25%) and adipocyte size (25%). At the transcript level, dietary PSRM decreased the lipid anabolic capacity and increased the lipid catabolic capacity in both the hepatopancreas and intraperitoneal fat tissues. Dietary PSRM attenuated enteritis-like histological features and reduced the mRNA levels of inflammation-related genes in the midgut of grass carp. Finally, several genes associated with anorexia were significantly upregulated when the dietary PSRM level reached 20%. Collectively, our study shows that diets supplemented with PSRM could improve growth, suppress lipid accumulation in the hepatopancreas and adipose tissue, and improve the intestinal health of juvenile grass carp. We suggest that the supplementation level of PSRM should be 5% for optimal results and should not exceed 20%.

Lipid Profile and Hepatic Fat Content Measured by 1H MR Spectroscopy in Patients before and after Liver Transplantation.

Increased hepatic fat content (HFC) is a hallmark of non-alcoholic fatty liver (NAFL) disease, a common condition in liver transplant recipients. Proton MR spectroscopy (1H MRS) and MR imaging-based proton density fat fraction as the only diagnosis modality enable precise non-invasive measurement of HFC and, also, fatty acid profiles in vivo. Using 1H MRS at 3T, we examined 47 liver transplantation candidates and 101 liver graft recipients. A point-resolved spectroscopy sequence was used to calculate the steatosis grade along with the saturated, unsaturated and polyunsaturated fractions of fatty acids in the liver. The steatosis grade measured by MRS was compared with the histological steatosis grade. HFC, represented by fat fraction values, is adept at distinguishing non-alcoholic steatohepatitis (NASH), NAFL and non-steatotic liver transplant patients. Relative hepatic lipid saturation increases while unsaturation decreases in response to increased HFC. Additionally, relative hepatic lipid saturation increases while unsaturation and polyunsaturation both decrease in liver recipients with histologically proven post-transplant NASH or NAFL compared to non-steatotic patients. HFC, measured by in vivo 1H MRS, correlated well with histological results. 1H MRS is a simple and fast method for in vivo analysis of HFC and its composition. It provides non-invasive support for NAFL and NASH diagnoses.

Effectiveness of drug interventions in nonalcoholic fatty liver disease: A network meta-analysis.

BACKGROUNDNonalcoholic fatty liver disease (NAFLD) is a major chronic liver disorder worldwide, and there is no established treatment for this disease. We conducted a network meta-analysis (NMA) to compare existing treatments, which include four classes of antidiabetic drugs, and examined the optimum treatments for NAFLD.AIMTo compare the effectiveness of different treatments for NAFLD.METHODSAn NMA was conducted using Stata 14.0 (Corporation LLC, College Station, United States) and R (X64 3.6.3 version) in this study. Eligible randomized controlled trials (RCTs) were searched in the PubMed, Cochrane Library, Embase, Medline and Web of Science databases from database inception to April 2021. Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference, respectively. An inconsistency model and “node-splitting” technique were used to test for inconsistency. Funnel plots were used to evaluate publication bias.RESULTSTwenty-two eligible RCTs involving 1377 participants were eventually included in our analysis. Data were pooled using a random-effects model. Our NMA results revealed that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were the most effective treatment, yielding improvements in hepatic fat content (HFC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum γ-glutamyl transferase (GGT) and body weight [surface under the cumulative ranking curve (SUCRA) = 99.6%, 92.6%, 82.8%, 92.3% and 99.6%, respectively], while thiazolidinediones (TZDs) were the best intervention for reducing the NAFLD activity score (NAS; SUCRA = 98.9%). In addition, moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups (SUCRA = 25.1%, 66.2%, 63.5%, 58.2% and 71.9% for HFC, ALT, AST, GGT and body weight, respectively). However, metformin performed poorly according to most indicators (SUCRA = 54.5%, 0.3%, 19.5%, 33.7%, 57.7% and 44.3% for HFC, NAS, ALT, AST, GGT and body weight, respectively).CONCLUSIONGLP-1RAs may be the optimum choice for most patients with NAFLD. However, TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Nonalcoholic Fatty Liver Disease: Indian Perspective.

Association between hepatic fat and subclinical vascular disease burden in the general population

ObjectiveIt is still controversial if increased hepatic fat independently contributes to cardiovascular risk. We aimed to assess the association between hepatic fat quantified by MRI and various subclinical vascular disease...

Lower brown adipose tissue activity is associated with non-alcoholic fatty liver disease but not changes in the gut microbiota

SummaryIn rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing. We transplanted gnotobiotic mice with feces from humans to assess the transferability of BAT activity through the microbiota. Individuals with NAFLD (n = 29) have lower BAT activity than those without, and BAT activity is inversely related to hepatic fat content. BAT activity is not related to the characteristics of the fecal microbiota and is not transmissible through fecal transplantation to mice. Thus, low BAT activity is associated with higher hepatic fat accumulation in human adults, but this does not appear to have been mediated through the gut microbiota.

Vitamin D and nonalcoholic fatty liver disease in children: a randomized controlled clinical trial.

Vitamin D is reported to have anti-inflammatory and insulin-sensitizing effects, yet vitamin D effects on hepatic fat content in children with nonalcoholic fatty liver disease (NAFLD) are not studied sufficiently. We aimed to evaluate the role of vitamin D supplementation on the hepatic fat content and NAFLD progression in children. This randomized controlled clinical trial was performed on 109 children with biopsy-proven NAFLD; only 100 patients completed the study. Patients were randomly assigned into two groups: the treatment group who received 2000IU/day vitamin D for 6months and the control group who received a placebo. Anthropometric measurements, vitamin D levels, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), serum triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), fasting blood glucose (FBG), fasting blood insulin level (FBI), homeostasis model assessment of insulin resistance (HOMA-IR), and serum calcium level were measured at the beginning and the end of the study. Liver biopsy was taken before and at the end of the study for all included children. There was a significant improvement of the hepatic steatosis and lobular inflammation by liver biopsy in the treatment group after treatment. However, there was no significant effect on the hepatocyte ballooning or hepatic fibrosis. There were significant decrease of AST, ALT, TG, LDL, FBG, FBI, and HOMA-IR and significant increase of vitamin D levels and HDL in the treatment group compared to the placebo group (P < 0.05).Conclusion: Vitamin D supplementation was found to be beneficial in the treatment of NAFLD in children.Trial registration: www.pactr.org , PACTR201710002634203. What is Known: • Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in pediatrics. • Several studies reported a negative association between low serum vitamin D level and grades of NAFLD. What is New: • Vitamin D supplementation has significantly decreased hepatic steatosis and lobular inflammation and improved the grades of NAFLD in children, confirmed by liver biopsy, but no effect on hepatocyte ballooning or fibrosis was observed. • Adjuvant vitamin D supplementation is recommended in children with NAFLD.

The Effect of Empagliflozin on Liver Fat in Type 2 Diabetes Mellitus Patients With Non-Alcoholic Fatty Liver Disease.

Background and objectiveThe prevalence of non-alcoholic fatty liver disease (NAFLD) is 60% in patients with type 2 diabetes mellitus (T2DM). NAFLD can lead to non-alcoholic steatohepatitis (NASH), both of which are the leading causes of cirrhosis. This study was undertaken to evaluate whether empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, reduces liver fat content in these patients after therapy.MethodsAfter enrolling patients of T2DM with NAFLD, they were administered empagliflozin 10 mg once daily orally for six months without modifying existing oral hypoglycemic agents (OHA) if any. All demographic data were collected, and anthropometric measurements, as well as laboratory investigations, were performed, and controlled attenuation parameter (CAP) and liver stiffness (LS) were measured using FibroScan® (Echosens, Paris, France) at baseline, and six months of therapy. The adverse effects related to therapy were also taken into account.ResultsThere was a significant decrease in mean CAP value from 282.07 ± 47.29 dB/m to 263.07 ± 49.93 dB/m and LS from 5.89 ± 4.23 kPa to 5.04 ± 1.49 kPa along with a significant decrease in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) among the patients. Compared to the baseline, there was a significant reduction in post-treatment weight, body mass index (BMI), and blood pressure (BP). The most commonly observed adverse effects of the therapy were urinary tract infection (UTI) (17.8%), nasopharyngitis (11.9%), and hypoglycemia (10.71%).ConclusionA reduction in hepatic fat content was seen in our prospective study cohort after six months of empagliflozin therapy. Empagliflozin also led to beneficial effects such as weight loss and reduction in transaminases and GGT. Given the absence of significant side effects of the therapy, empagliflozin could be used as an effective treatment modality for T2DM patients with NAFLD, which are two conditions commonly seen in combination.

Correlation guided Network Integration (CoNI) reveals novel genes affecting hepatic metabolism

ObjectiveTechnological advances have brought a steady increase in the availability of various types of omics data, from genomics to metabolomics. Integrating these multi-omics data is a chance and challenge for systems biology; yet, tools to fully tap their potential remain scarce. MethodsWe present here a fully unsupervised and versatile correlation-based method – termed Correlation guided Network Integration (CoNI) – to integrate multi-omics data into a hypergraph structure that allows for the identification of effective modulators of metabolism. Our approach yields single transcripts of potential relevance that map to specific, densely connected, metabolic subgraphs or pathways. ResultsBy applying our method on transcriptomics and metabolomics data from murine livers under standard Chow or high-fat diet, we identified eleven genes with potential regulatory effects on hepatic metabolism. Five candidates, including the hepatokine INHBE, were validated in human liver biopsies to correlate with diabetes-related traits such as overweight, hepatic fat content, and insulin resistance (HOMA-IR). ConclusionOur method's successful application to an independent omics dataset confirmed that the novel CoNI framework is a transferable, entirely data-driven, flexible, and versatile tool for multiple omics data integration and interpretation.

Effect of a Training Program on Hepatic Fat Content and Cardiometabolic Risk in Postmenopausal Women: The Randomized Controlled Trial

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 &lt; 0.001), though EX+ EMS experienced better improvements (p &lt; 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.

Hepatic fat quantification of magnetic resonance imaging whole-liver segmentation for assessing the severity of nonalcoholic fatty liver disease: comparison with a region of interest sampling method.

Accurate and early assessment of the hepatic fat content is crucial for patients with nonalcoholic fatty liver disease (NAFLD). For years, magnetic resonance imaging (MRI) has been considered the optimal noninvasive method for the assessment of fat accumulation. To avoid time-consuming manual placement of multiple regions of interest (ROI), the use of whole-liver segmentation has been proposed to measure liver fat, mainly for heterogeneous fat deposition. However, it remains uncertain whether the hepatic mean fat fraction (FF) obtained by whole-liver segmentation with the inclusion of intrahepatic vasculature is consistent with the traditional ROI sampling method. In this study, we assessed the accuracy of hepatic mean FF obtained by whole-liver segmentation in patients of NAFLD with different severities using the ROI sampling method as a reference standard. Hepatic FFs were measured by whole-liver segmentation and the ROI sampling method (reference standard) using MRI scanning with the iterative decomposition of water and fat with echo an asymmetry at least-square estimation-iron quantification (IDEAL-IQ) sequence. SPSS version 25.0 software was used to analyze the correlation and consistency of data between the two methods. There was a strong correlation in hepatic FF between whole-liver segmentation and the ROI sampling method in healthy, mild, and moderate steatosis patients (r = 0.943, 0.990, and 0.961, respectively). Bland-Altman analysis showed a small bias of +0.50±0.27 and +0.05±0.30, which indicated a small overestimation when using whole-liver segmentation in healthy subjects and mild NAFLD patients. The 95% limits of agreement ranged from +1.02 to -0.03, and from +0.65 to -0.55, respectively. However, a small bias of -0.96±0.77 was also evident, which indicated a small underestimation when using whole-liver segmentation in moderate NAFLD patients. The 95% limits of agreement ranged from +0.56 to -2.48. Due to inclusion of the intrahepatic vasculature, whole-liver segmentation has some effects on hepatic FF assessment in patients with different NAFLD severities; yet, it does not significantly affect the assessment of whole-liver FF in MRI FF maps.